Obsessive Compulsive Disorder - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

OBSESSIVE COMPULSIVE DISORDER A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES

J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS

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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright 2004 by ICON Group International, Inc. Copyright 2004 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1

Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Obsessive Compulsive Disorder: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-597-84133-0 1. Obsessive Compulsive Disorder-Popular works. I. Title.

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Disclaimer This publication is not intended to be used for the diagnosis or treatment of a health problem. It is sold with the understanding that the publisher, editors, and authors are not engaging in the rendering of medical, psychological, financial, legal, or other professional services. References to any entity, product, service, or source of information that may be contained in this publication should not be considered an endorsement, either direct or implied, by the publisher, editors, or authors. ICON Group International, Inc., the editors, and the authors are not responsible for the content of any Web pages or publications referenced in this publication.

Copyright Notice If a physician wishes to copy limited passages from this book for patient use, this right is automatically granted without written permission from ICON Group International, Inc. (ICON Group). However, all of ICON Group publications have copyrights. With exception to the above, copying our publications in whole or in part, for whatever reason, is a violation of copyright laws and can lead to penalties and fines. Should you want to copy tables, graphs, or other materials, please contact us to request permission (E-mail: [email protected]). ICON Group often grants permission for very limited reproduction of our publications for internal use, press releases, and academic research. Such reproduction requires confirmed permission from ICON Group International Inc. The disclaimer above must accompany all reproductions, in whole or in part, of this book.

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Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on obsessive compulsive disorder. Books in this series draw from various agencies and institutions associated with the United States Department of Health and Human Services, and in particular, the Office of the Secretary of Health and Human Services (OS), the Administration for Children and Families (ACF), the Administration on Aging (AOA), the Agency for Healthcare Research and Quality (AHRQ), the Agency for Toxic Substances and Disease Registry (ATSDR), the Centers for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA), the Healthcare Financing Administration (HCFA), the Health Resources and Services Administration (HRSA), the Indian Health Service (IHS), the institutions of the National Institutes of Health (NIH), the Program Support Center (PSC), and the Substance Abuse and Mental Health Services Administration (SAMHSA). In addition to these sources, information gathered from the National Library of Medicine, the United States Patent Office, the European Union, and their related organizations has been invaluable in the creation of this book. Some of the work represented was financially supported by the Research and Development Committee at INSEAD. This support is gratefully acknowledged. Finally, special thanks are owed to Tiffany Freeman for her excellent editorial support.

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About the Editors James N. Parker, M.D. Dr. James N. Parker received his Bachelor of Science degree in Psychobiology from the University of California, Riverside and his M.D. from the University of California, San Diego. In addition to authoring numerous research publications, he has lectured at various academic institutions. Dr. Parker is the medical editor for health books by ICON Health Publications. Philip M. Parker, Ph.D. Philip M. Parker is the Eli Lilly Chair Professor of Innovation, Business and Society at INSEAD (Fontainebleau, France and Singapore). Dr. Parker has also been Professor at the University of California, San Diego and has taught courses at Harvard University, the Hong Kong University of Science and Technology, the Massachusetts Institute of Technology, Stanford University, and UCLA. Dr. Parker is the associate editor for ICON Health Publications.

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About ICON Health Publications To discover more about ICON Health Publications, simply check with your preferred online booksellers, including Barnes&Noble.com and Amazon.com which currently carry all of our titles. Or, feel free to contact us directly for bulk purchases or institutional discounts: ICON Group International, Inc. 4370 La Jolla Village Drive, Fourth Floor San Diego, CA 92122 USA Fax: 858-546-4341 Web site: www.icongrouponline.com/health

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Table of Contents FORWARD .......................................................................................................................................... 1 CHAPTER 1. STUDIES ON OBSESSIVE COMPULSIVE DISORDER ......................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Obsessive Compulsive Disorder.................................................... 5 E-Journals: PubMed Central ....................................................................................................... 56 The National Library of Medicine: PubMed ................................................................................ 57 CHAPTER 2. NUTRITION AND OBSESSIVE COMPULSIVE DISORDER ............................................... 91 Overview...................................................................................................................................... 91 Finding Nutrition Studies on Obsessive Compulsive Disorder .................................................. 91 Federal Resources on Nutrition ................................................................................................... 93 Additional Web Resources ........................................................................................................... 93 CHAPTER 3. ALTERNATIVE MEDICINE AND OBSESSIVE COMPULSIVE DISORDER ......................... 95 Overview...................................................................................................................................... 95 National Center for Complementary and Alternative Medicine.................................................. 95 Additional Web Resources ........................................................................................................... 98 General References ....................................................................................................................... 98 CHAPTER 4. DISSERTATIONS ON OBSESSIVE COMPULSIVE DISORDER ........................................... 99 Overview...................................................................................................................................... 99 Dissertations on Obsessive Compulsive Disorder ....................................................................... 99 Keeping Current ........................................................................................................................ 100 CHAPTER 5. CLINICAL TRIALS AND OBSESSIVE COMPULSIVE DISORDER.................................... 101 Overview.................................................................................................................................... 101 Recent Trials on Obsessive Compulsive Disorder ..................................................................... 101 Keeping Current on Clinical Trials ........................................................................................... 106 CHAPTER 6. PATENTS ON OBSESSIVE COMPULSIVE DISORDER .................................................... 109 Overview.................................................................................................................................... 109 Patents on Obsessive Compulsive Disorder............................................................................... 109 Patent Applications on Obsessive Compulsive Disorder........................................................... 118 Keeping Current ........................................................................................................................ 129 CHAPTER 7. BOOKS ON OBSESSIVE COMPULSIVE DISORDER ....................................................... 131 Overview.................................................................................................................................... 131 Book Summaries: Federal Agencies............................................................................................ 131 Book Summaries: Online Booksellers......................................................................................... 132 The National Library of Medicine Book Index ........................................................................... 135 Chapters on Obsessive Compulsive Disorder ............................................................................ 135 CHAPTER 8. MULTIMEDIA ON OBSESSIVE COMPULSIVE DISORDER............................................. 137 Overview.................................................................................................................................... 137 Bibliography: Multimedia on Obsessive Compulsive Disorder ................................................. 137 CHAPTER 9. PERIODICALS AND NEWS ON OBSESSIVE COMPULSIVE DISORDER.......................... 139 Overview.................................................................................................................................... 139 News Services and Press Releases.............................................................................................. 139 Newsletter Articles .................................................................................................................... 141 Academic Periodicals covering Obsessive Compulsive Disorder ............................................... 141 CHAPTER 10. RESEARCHING MEDICATIONS................................................................................. 143 Overview.................................................................................................................................... 143 U.S. Pharmacopeia..................................................................................................................... 143 Commercial Databases ............................................................................................................... 144 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 147 Overview.................................................................................................................................... 147 NIH Guidelines.......................................................................................................................... 147

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NIH Databases........................................................................................................................... 149 Other Commercial Databases..................................................................................................... 151 The Genome Project and Obsessive Compulsive Disorder......................................................... 151 APPENDIX B. PATIENT RESOURCES ............................................................................................... 155 Overview.................................................................................................................................... 155 Patient Guideline Sources.......................................................................................................... 155 Associations and Obsessive Compulsive Disorder..................................................................... 157 Finding Associations.................................................................................................................. 158 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 161 Overview.................................................................................................................................... 161 Preparation................................................................................................................................. 161 Finding a Local Medical Library................................................................................................ 161 Medical Libraries in the U.S. and Canada ................................................................................. 161 ONLINE GLOSSARIES................................................................................................................ 167 Online Dictionary Directories ................................................................................................... 168 OBSESSIVE COMPULSIVE DISORDER DICTIONARY ..................................................... 169 INDEX .............................................................................................................................................. 229

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FORWARD In March 2001, the National Institutes of Health issued the following warning: "The number of Web sites offering health-related resources grows every day. Many sites provide valuable information, while others may have information that is unreliable or misleading."1 Furthermore, because of the rapid increase in Internet-based information, many hours can be wasted searching, selecting, and printing. Since only the smallest fraction of information dealing with obsessive compulsive disorder is indexed in search engines, such as www.google.com or others, a non-systematic approach to Internet research can be not only time consuming, but also incomplete. This book was created for medical professionals, students, and members of the general public who want to know as much as possible about obsessive compulsive disorder, using the most advanced research tools available and spending the least amount of time doing so. In addition to offering a structured and comprehensive bibliography, the pages that follow will tell you where and how to find reliable information covering virtually all topics related to obsessive compulsive disorder, from the essentials to the most advanced areas of research. Public, academic, government, and peer-reviewed research studies are emphasized. Various abstracts are reproduced to give you some of the latest official information available to date on obsessive compulsive disorder. Abundant guidance is given on how to obtain free-of-charge primary research results via the Internet. While this book focuses on the field of medicine, when some sources provide access to non-medical information relating to obsessive compulsive disorder, these are noted in the text. E-book and electronic versions of this book are fully interactive with each of the Internet sites mentioned (clicking on a hyperlink automatically opens your browser to the site indicated). If you are using the hard copy version of this book, you can access a cited Web site by typing the provided Web address directly into your Internet browser. You may find it useful to refer to synonyms or related terms when accessing these Internet databases. NOTE: At the time of publication, the Web addresses were functional. However, some links may fail due to URL address changes, which is a common occurrence on the Internet. For readers unfamiliar with the Internet, detailed instructions are offered on how to access electronic resources. For readers unfamiliar with medical terminology, a comprehensive glossary is provided. For readers without access to Internet resources, a directory of medical libraries, that have or can locate references cited here, is given. We hope these resources will prove useful to the widest possible audience seeking information on obsessive compulsive disorder. The Editors

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From the NIH, National Cancer Institute (NCI): http://www.cancer.gov/cancerinfo/ten-things-to-know.

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CHAPTER 1. DISORDER

STUDIES ON OBSESSIVE COMPULSIVE

Overview In this chapter, we will show you how to locate peer-reviewed references and studies on obsessive compulsive disorder.

The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and obsessive compulsive disorder, you will need to use the advanced search options. First, go to http://chid.nih.gov/index.html. From there, select the “Detailed Search” option (or go directly to that page with the following hyperlink: http://chid.nih.gov/detail/detail.html). The trick in extracting studies is found in the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Journal Article.” At the top of the search form, select the number of records you would like to see (we recommend 100) and check the box to display “whole records.” We recommend that you type “obsessive compulsive disorder” (or synonyms) into the “For these words:” box. Consider using the option “anywhere in record” to make your search as broad as possible. If you want to limit the search to only a particular field, such as the title of the journal, then select this option in the “Search in these fields” drop box. The following is what you can expect from this type of search: •

Erectile Dysfunction: The Role of Concomitant Diseases Source: Physician Assistant. 24(6 Supplement): 12-16. June 2000. Contact: Available from Springhouse Corporation. Physician Assistant Journal, 1111 Bethlehem Pike, P.O. Box 908, Springhouse, PA 19477-0908. (215) 628-7758 or (800) 7834903. Website: www.pajournal.com. Summary: An estimated 20 to 30 million men and their partners are affected by erectile dysfunction (ED). However, patients and health care providers can often be uncomfortable discussing the subject. Understanding the causes of ED, which can range from alterations in the hemodynamics of penile blood flow to hormonal imbalances, can

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be helpful in dispelling the embarrassment and discomfort surrounding this disorder. Written for physician assistants, this article reviews the causes and concomitant diseases associated with ED, as well as the importance of early recognition and patient education. Hypertension (high blood pressure), arteriosclerosis (deposits of plaque in the arteries, causing 'hardening'), and lipid disorders are frequently associated with ED. Diabetes can affect the microvasculature (small blood vessels) of the nerves that regulate blood flow to and from the penis. Medications used to treat common diseases such as hypertension, cardiovascular disorders, and depression can precipitate ED, as can medications used for decongestion and appetite suppression. The causes of ED are categorized in three groups: organic, psychogenic, and mixed (organic and psychogenic). Psychogenic causes of ED include depression, anxiety, stress related disorders, religious orthodoxy, obsessive compulsive disorder, anhedonia, sexual phobias, and sexual deviance. The author stresses that if the clinician can identify an erectile problem early, psychosocial sequelae such as embarrassment, anxiety, self doubt, depression, withdrawal from relationships, divorce, or other problems may be averted. One table lists common drugs that can affect erectile function; another table reprints a five item sexual health inventory for men. 3 tables. 10 references. •

Recognition and Management of Tourette's Syndrome and Tic Disorders Source: American Family Physician. 59(8): 2263-2272. April 15, 1999. Summary: This article reviews the recognition and management of Tourette's syndrome and tic disorders, conditions that primary care physicians are likely to encounter. Up to 20 percent of children have at least a transient tic disorder at some point. Once believed to be rare, Tourette's syndrome is now known to be a more common disorder that represents the most complex and severe manifestation of the spectrum of tic disorders. Tourette's syndrome is characterized by both motor and vocal tics, with onset in childhood. Tourette's syndrome is a chronic familial disorder with a fluctuating course; the long term outcome is generally favorable. Although the exact underlying pathology has yet to be determined, evidence indicates a disorder localized to the frontal subcortical neural pathways. Tourette's syndrome is commonly associated with attention deficit hyperactivity disorder (ADHD), obsessive compulsive disorder, behavior problems, and learning disabilities. These comorbid conditions make the management of Tourette's syndrome more challenging. Management of Tourette's syndrome should include timely and accurate diagnosis, education, and behavior or pharmacologic interventions. The use of neuroleptic medications and dopamine D2 antagonist drugs can be effective, but may be associated with significant side effects. 3 figures. 5 tables. 32 references.

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Psychodermatology: The Mind and Skin Connection Source: American Family Physician. 64(11): 1873-1878. December 1, 2001. Contact: Available from American Academy of Family Physicians. 11400 Tomahawk Creek Parkway, Leawood, KS 66211-2672. (800) 274-2237 or (913) 906-6000. E-mail: [email protected]. Website: www.aafp.org. Summary: This journal article provides health professionals with information on the classification and management of psychodermatologic disorders. A psychodermatologic disorder is a condition that involves an interaction between the mind and the skin. Psychodermatologic disorders can be broadly classified into psychophysiologic disorders, primary psychiatric disorders, and secondary psychiatric disorders. Psychophysiologic disorders, such as psoriasis and eczema, are conditions that are

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frequently precipitated or exacerbated by emotional stress. Stress management classes, relaxation techniques, music, or exercise may benefit patients whose skin condition is precipitated or exacerbated by stress. Drug therapy with antianxiety medication may also be helpful. Primary psychiatric disorders involve conditions that result in self induced cutaneous manifestations, such as trichotillomania and delusions of parasitosis. Trichotillomania is a condition in which a person pulls out his or her own hair. A skin biopsy can be helpful in determining the diagnosis because the hair root undergoes a unique change called trichomalacia. Drugs used in the treatment of obsessive compulsive disorder can be helpful in the pharmacologic management of trichotillomania. Patients with delusions of parasitosis believe that their bodies are infested by some type of organism. The treatment for this condition is an antipsychotic medication called pimozide. The terms neurotic excoriations and psychologic excoriations are used when patients self inflict excoriations with their fingernails. Factitial dermatitis generally refers to a condition in which the patient uses something more elaborate than the fingernails to damage his or her skin. Tricyclic antidepressants may be used to treat these primary psychiatric disorders. Secondary psychiatric disorders are associated with disfiguring skin disorders. This disfigurement results in psychiatric problems, such as decreased self esteem, depression, or social phobia. 6 figures, 3 tables, and 21 references. (AA-M).

Federally Funded Research on Obsessive Compulsive Disorder The U.S. Government supports a variety of research studies relating to obsessive compulsive disorder. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.2 CRISP (Computerized Retrieval of Information on Scientific Projects) is a searchable database of federally funded biomedical research projects conducted at universities, hospitals, and other institutions. Search the CRISP Web site at http://crisp.cit.nih.gov/crisp/crisp_query.generate_screen. You will have the option to perform targeted searches by various criteria, including geography, date, and topics related to obsessive compulsive disorder. For most of the studies, the agencies reporting into CRISP provide summaries or abstracts. As opposed to clinical trial research using patients, many federally funded studies use animals or simulated models to explore obsessive compulsive disorder. The following is typical of the type of information found when searching the CRISP database for obsessive compulsive disorder: •

Project Title: 38 WEEK, MULTICENTER STUDY WITH OBSESSIVE COMPULSIVE DISORDER Principal Investigator & Institution: Riddle, Mark A.; Professor; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2001 Summary: The importance of developing more effective treatments for obsessive compulsive disorder (OCD) is underscored by recent epidemiological data suggesting

2 Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).

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that previious studies may have underestimated the prevalence of OCD in the general population by as much as 20-fold. The life time prevalence for the disorder is between 2 and 3%. Children and adolescents are frequently affected by OCD: nearly 80% of adult patients have their onset in childhood or adolescence. The key clinical features of OCD are strikingly similar between children, adolescents and adults. These features consist of recurrent obsessional thoughts or impulses, and/or repetitive, purposeful and intentional (i.e., compulsive) behaviours that are performed in response to an obsession or certain rules. The obsessions & compulsions cause marked distress, are time consuming or significantly interfere with the youngster;s normal routine, school functioning or usual social activities or relationships. Phase I of this study is a 16 week,open label phase. Phase II is a 16 week double-blind discontinuation phase followed by a 6 week double- blind down titration. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: A MOUSE BEHAVIORAL BATTERY FOR DOMAINS OF CNS FUNCTION Principal Investigator & Institution: Paylor, Richard E.; Assistant Professor; Molecular and Human Genetics; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2001; Project Start 01-MAR-2000; Project End 28-FEB-2003 Summary: (Adapted from applicant's abstract): By virtue of the synteny between mouse and human, identifying genes that regulate behavioral responses in mice will provide important insights into the function of these genes in man. However, because behavioral responses are different between inbred strains of mice, the success of future studies using mouse models to identify genes underlying behavioral traits will require investigators to carefully choose the background strain for creating any particular mutation. Thus, it will be important for investigators to have sufficient information about the behavioral responses of different inbred strains of mice on a wide variety of assays. The objective of the research in this proposal is to characterize the behavioral responses of at least 6 inbred strains of mice on a wide variety of behavioral tests, and to develop a database that is easily accessed by investigators across the world. Three specific aims have been formulated to reach this objective. The first specific aim is to characterize the behavioral responses of inbred mice on a high-throughput behavioral test battery. The second aim is to develop clusters of behavioral assays specific to particular domains of CNS function that can be used as a secondary screen to further understand behavioral phenotypes of mutant mice. Six inbred strains will be characterized on each cluster developed under Specific Aim 2. The final specific aim is to characterize developmental profiles for several behavioral responses in different inbred strains of mice. Studying the development of behavior will provide important insights into the maturation of the processes underlying behavior, and will provide critical information for future studies with mutant mice that could eventually save thousands of research dollars. Findings from these aims will provide an important set of data on inbred strains of mice that will be critical to future studies developing mouse genetic models to better understand the genetic basis for several behavioral abnormalities associated with different human diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: AUTISM AND ADHD: EXECUTIVE FUNCTION AND BRAIN MECHANISMS Principal Investigator & Institution: Goldberg, Melissa C.; Kennedy Krieger Research Institute, Inc. Baltimore, Md 21205

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Timing: Fiscal Year 2001; Project Start 07-SEP-2000; Project End 30-JUN-2005 Summary: This Mentored Scientist Award will develop the candidate, a cognitivedevelopmental research psychologist, into an independent investigator in the field of child psychology. The candidate's long-range goals are to apply the knowledge attained to understand brain-behavior relationships in the pathogenesis of autism, Attention Deficits Hyperactivity Disorder, and other child mental disorders, such as Anxiety, Obsessive Compulsive Disorder, and Tourette's syndrome. The specific research project aims to understand: 1) a constellation of executive functions that differentiate children with autism and children with ADHD; and 2) brain mechanisms that underlie executive function impairment in these two disorders. Cognitive-neuropsychological research paradigms, morphometric, and functional magnetic resonance imaging (fMRI) will be used to examine the hypothesis that autism and ADHD are each related to specific dysfunctions within an anterior frontal brain network. This project provides for the candidate's career development through formal study of childhood psychiatric disorders, course-work, workshops in fMRI, extensive mentorship in a clinical-research environment, and implementation of a research project that is the beginning of a larger investigation aimed at understanding the neurobiological bases of complex child psychiatric disorders. Innovative neuroimaging techniques can provide detailed information about patterns of brain activity associated with sensory, perceptual, and cognitive processes that may be used to test, define, and differentiate between psychological theories of autism and ADHD and may give rise to improved diagnoses and treatments. Dr. Godfrey Pearlson, an expert in neuroimaging of mental disorders, will provide primary mentorship. A number of consultants will supplement the mentor's areas of expertise. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: AUTOIMMUNE NEUROPSYCHIATRIC DISORDERS

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Principal Investigator & Institution: Trifiletti, Rosario R.; Assistant Professor; Weill Medical College of Cornell Univ New York, Ny 10021 Timing: Fiscal Year 2001; Project Start 01-DEC-2000; Project End 30-NOV-2001 Summary: Recent evidence suggests that Sydenham chorea, obsessive/compulsive disorder and Tourette syndrome may have a similar autoimmune basis. Dr. Zabriskie and co-workers have shown that a specific B-cell D8/17 clonal marker is greatly expanded in all of these groups. The goal of the present study is to correlate brain autoantigens, B-cell clonal status and neurologic, psychaitric and cognitive outcome in all of these groups. If correlations are found, efforts will be made to isolate the respective autoantigens. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: AUTOMATION OF MENTAL CONTROL Principal Investigator & Institution: Wegner, Daniel M.; Professor; Psychology; Harvard University Holyoke Center 727 Cambridge, Ma 02138 Timing: Fiscal Year 2001; Project Start 01-JUN-1992; Project End 31-JAN-2003 Summary: (Applicant's Abstract): Effective social interaction and personal adaptation requires that people often try to influence their own minds. People engage in such mental control when they try to stop thinking about something, for example, or when they attempt to avoid unwanted or inappropriate emotions or desires. Attempts to control mental states often fail, however, and past research suggests that this happens

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because mental control produces ironic processes unconscious failure-monitoring processes that promote the appearance of the mental states people most hope to avoid. This is why unwanted thoughts and emotions often arise at precisely the worst times. The specific aim of this project is to see whether such ironic processes are overcome when mental control is practiced repeatedly and becomes automatized Like any practiced skill, mental control should become more effective with rehearsal, and this research examines its possibility by focusing both on rehearsal of mental control in the laboratory and on the testing of special populations who are likely to have engaged in chronic mental control in the past. But also like any skill that has become automatic, mental control can be disrupted whenever the person renews conscious control and monitoring of the process. This fragile automaticity hypothesis is tested in these studies, to see whether remembering that one is trying to control one's mind can reintroduce ironic thoughts and emotions even after mental control has become automatic. This research should have several key implications for mental health. The automatization of mental control processes, and its accompanying fragile automaticity, may be implicated in the etiology of depression, obsessive-compulsive disorder, and eating disorders, and may also underlie social interfactional problems that arise from error in the control of socially inappropriate behavior. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BASAL GANGLIA AND 5-HT IN RITUALISTIC SOCIAL DISPLAYS Principal Investigator & Institution: Baxter, Lewis R.; Vice Chair; Psychiatry & Behav Neurobiol; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2001; Project Start 27-SEP-2001; Project End 31-AUG-2006 Summary: (provided by applicant): Ritualistic displays of social/territorial status are important regulators of intra-species interactions, reducing costs of competition for both individuals, and the group. Such ritualistic behaviors have similar forms across a wide range of land vertebrates (anmiotes). When the brain mechanisms mediating them dysfunction in man, the result may be certain psychopathologies, such as those characteristic of obsessive compulsive disorder (OCD), Tourette's disorder (GTS), social phobia, and some mood disorders. Functional neuroimaging studies by the Principal Investigator and others suggest that cortico/limbic-basal ganglionic-thalamic (=BG) systems mediate symptoms seen in OCD and related depressions. Work with Anolis lizards suggest that amniote- generic dorsolateral (DL) vs. ventro-medial (VM) BG systems mediate generic dominant vs. submissive social displays, respectively. This work has also demonstrated an acute role for serotomn (5-HT) in determining whether dominant or submissive behaviors are expressed in a given context, and strongly suggest that Anolis 5-HTIB receptors determines the differential 5-HT flux related to dominant vs. submissive behavior. Our human and lizard findings together have lead to a thesis that BG systems are organized as cross-inhibitory DL vs. VM subsystems that interact to bias behavior toward generic dominant vs. submissive behavioral routines. When DL/VM BQ subsystem interactions dysfunction in humans, the result may be fixed, context-inappropriate behaviors, as seen in OCD/depressions (submissive/ defeat), thus explaining the human PET findings. Conversely, aggressive states with stereotypic displays of dominance behavior (e.g., mania ,QTS), might have reciprocal BG system dysfunctions. Thus, a fuller understanding of how BQ systems interact and are regulated by 5-HT functions to mediate social/territorial display behaviors in an appropriate, easily manipulated model system is of value. By using pharmacological challenges, in vivo functional autoradiography, and in situ hybridization, we propose to elucidate the proximate BG mechanisms by which male Anolis lizards are vectored to

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display dominant vs. subordinate social/territorial behavioral routines, and how these behaviors and their mediating brain functions are switched between these poles of status as a result of social/conflict experience. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BASAL GANGLIA FUNCTION IN OBSESSIVE COMPULSIVE DISORDER Principal Investigator & Institution: Rauch, Scott L.; Associate Professor; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2001; Project Start 01-AUG-1999; Project End 31-JUL-2004 Summary: The goals of this project are to test specific hypotheses about the pathophysiology of obsessive compulsive disorder (OCD) using functional MRI (fMRI) and cognitive neuroscience methods. The basal ganglia have been implicated in the pathophysiology of OCD and also in the normal mediating anatomy of implicit (i.e., nonconscious) learning. We have developed an fMRI paradigm to measure activity within components of the basal ganglia during the performance of an implicit learning task. In preliminary functional imaging studies, we have observed an abnormal activation profile in medication-free subjects with current OCD. Specifically, in comparison to normal control subjects, patients with OCD exhibit a failure to activate right striatum, and an absence of thalamic deactivation, as well as aberrent medial temporal activation (i.e., not found in normal subjects). These results are consistent with evolving neurobiological models of OCD and basal ganglia function. The current proposal aims to: 1) use this fMRI paradigm to replicate and elaborate upon the above findings in a larger cohort of medication-free patients with active OCD and matched normal comparison subjects; 2) determine the specificity of the findings in OCD by studying psychiatric comparison subjects; and 3) further investigate the neuropsychological consequences of the abnormal activation profile observed in OCD. It is anticipated that this approach will yield new information regarding the pathophysiology of OCD and related disorders, while providing new insights about the normal function of the basal ganglia and the mediating anatomy of normal learning. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: BASAL GANGLIA FUNCTION: GLOBUS PALLIDUS NEURONS Principal Investigator & Institution: Hanson, Jesse E.; Biology; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2001; Project Start 08-FEB-2001 Summary: The overall objective of this work is to understand the function of the basal ganglia in both the normal and diseased states. Pathology of the basal ganglia leads to several mental health disorders including dementias due to Parkinson's and Huntington's Disease as well as Obsessive Compulsive Disorder and Tourette's Syndrome. However, little is known about the precise function of the basal ganglia circuit must be formed. The goal of this project is to understand how neurons in the Globus Pallidus (GP), a nucleus in the basal ganglia, process inputs. By understanding how the intrinsic properties these neurons interact with thousands of synaptic inputs to form a single output spike train, sight into the function of this stage of the basal ganglia circuit may be obtained. Specifically the distribution of intrinsic conductances will be examined using antibody labeling observed with electron microscopy. A compartmental model of single neurons will be made incorporating this information. This model will be used to probe the input-output function of GP neurons. The insight gained from this

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model will be related to real neurons by testing predictions of the model in living neurons, using in vitro electrophysiological recordings with simulated synaptic inputs. This approach of integrating information from experimental measurements and model simulations will provide a description of how these neurons process inputs. The knowledge gained by this study will provide an important piece of the puzzle in the effort to understand normal and diseased function of the basal ganglia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BEHAVIOR THERAPY FOR CHILDHOOD OCD Principal Investigator & Institution: Piacentini, John C.; Associate Professor; None; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2001; Project Start 01-DEC-1998; Project End 30-NOV-2002 Summary: This is a resubmission of an application to support the controlled evaluation of a standardized multicomponent cognitive behavioral treatment program for child and adolescent Obsessive-Compulsive Disorder (OCD). The treatment program consists of individual exposure plus response prevention (ERP) for the OCD child plus a concurrent family intervention designed to reduce OCD-related family conflict, facilitate family disengagement from the affected child's OCD behavior, and rebuild normal family interaction patterns. A total of eighty (80) medication- free youngsters and their families will be randomly assigned to receive either the combined ERP/Family Treatment Program (n=56) or a comparison treatment, Relaxation Training (RT) (n=24). Both treatments will be delivered over 12 90 minute outpatient sessions according to detailed treatment manuals. RT was selected as the comparison treatment because of its credibility as an anxiety treatment and familiarity to potential subjects. RT has been used as a comparison condition for at least two randomized controlled ERP trials for adult OCD and shown to be ineffective in treating this disorder. OCD is a chronic, often disabling disorder in childhood. Preliminary studies suggest that ERP is an effective treatment for children with OCD although no controlled trials to this effect have been published. OCD in childhood has been associated with increased rates of parental psychopathology and significant disruptions in family relationships and functioning. Moreover, family contextual variables have been associated with both a worse treatment response and a poorer long-term outcome. Although it has long been hypothesized that family participation in treatment may be helpful, this is the first controlled study incorporating a systematic manualized family treatment component. Youngsters and families will undergo comprehensive, systematic, including behavioral, assessments by blind clinical evaluators at baseline, monthly during treatment, posttreatment, and two follow-up evaluations over six months. Treatment outcome will be examined in multimodal fashion and across multiple functional domains with a special emphasis on family contextual variables. The impact of baseline functioning, including family context, and initial change over time on treatment outcome will also be systematically evaluated. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: BRAIN IMAGING OF CHILDHOOD ONSET PSYCHIATRIC DISORDERS, ENDOCRINE DISORDERS Principal Investigator & Institution: Giedd, Jay N.; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2001

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Summary: Cerebral MRI will be used to assess brain anatomy and function in normal volunteers and subjects with a variety of childhood onset psychiatric disorders including attention deficit disorder, autism, congenital adrenal U hyperplasia. childhood-onset schizophrenia. dyslexia, multidimensional impairment syndrome. obsessive compulsive disorder, Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infection (PANDAS), stuttering, Sydenham's chorea, and Tourette's Syndrome. Quantitative measures of brain structure and function will be compared across age, gender. and diagnostic groups. Correlations between brain and behavioral measures will be examined for normal and clinical populations. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CBT AUGMENTATION OF SRI PHARMACOTHERAPY FOR OCD Principal Investigator & Institution: Liebowitz, Michael R.; New York State Psychiatric Institute 1051 Riverside Dr New York, Ny 10032 Timing: Fiscal Year 2001; Project Start 01-AUG-1990; Project End 30-JUN-2005 Summary: (Adapted from the Applicant's Abstract): This is one-half of a two-site study proposed jointly by Foa and Franklin at the University of Pennsylvania, and Liebowitz and Simpson at Columbia University, who are submitting separate but similar proposals (collaborative CSMD). Obsessive-compulsive disorder (OCD) is prevalent, chronic, and debilitating. Both cognitive behavior therapy (CBT) by exposure and ritual prevention (EX/RP) and serotonin reuptake inhibitors (SRIs) are recommended for OCD. However, recommended doses of the widely used SRIs leave many patients with substantial residual symptoms and a need for more help. This proposal addresses an important problem in treating OCD: how to augment the limited efficacy of SRIs. This study will examine the immediate and long-term value of adding an established CBT for OCD, i.e., EX/RP, to continuing SRI treatment, for reducing residual symptoms and increasing general functioning. Participants will be 136 individuals (68/site) with clinically significant OCD despite having benefited somewhat from an adequate trial of a SRI. While continuing on an SRI, patients will be randomized to adjunctive EX/RP or another CBT, Stress Management Training (SMT). SMT targets generalized anxiety symptoms, but has not been found effective for OCD. As a credible comparison therapy, SMT will control for time, attention, and other non-specific effects of CBT. Both adjunctive CBT treatments will occur twice a week for 2 months. Responders will enter a 6 month Maintenance Phase, during which they will continue their medication and receive monthly 45 min. maintenance sessions. Those who remain in remission will then enter a 6 month Follow-up Phase, in which they will be allowed to reduce or discontinue medication, and will have no further CBT. Non-responders and relapsers will be treated appropriately and evaluated every 3 months. Assessments will focus on OCD symptoms and on general functioning; they will occur during an Acute Phase (0, 1, 2 mos) and every 3 months thereafter (5, 8, 11, 14 months). The proposed sample will allow sufficient power to test both treatment and site effects. This study has several unique features. 1. It offers a model for pharmacotherapy-psychotherapy studies because experts in each modality will deliver both treatments; this guards against expert biases for either treatment. 2. We wanted the results to be directly applicable to OCD patients seen in routine clinical practice. Accordingly, exclusion criteria are few. 3. The EX/RP protocol was designed to maintain efficacy while maximizing practicality. 4. Patients who are unable to remain in the treatment protocol for any reason will continue to be assessed; this will allow us to describe the long-term outcome of the whole sample. Long-term goals are: a) to provide clinicians with new strategies for treating OCD

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patients who remain symptomatic despite an adequate trial of a SRI and b) to establish effective treatments that reduces the considerable social costs of unremittant OCD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CODING OF BEHAVIORAL SEQUENCES IN THE BASAL GANGLIA Principal Investigator & Institution: Aldridge, J Wayne.; Senior Associate Research Scientist; Neurology; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2001; Project Start 01-MAY-1995; Project End 30-JUN-2003 Summary: (Adapted from applicant's abstract): The goal of this project is to understand the neuronal mechanisms of the basal ganglia that mediate sequences of behavior. Studies in humans indicate that sequence control, especially the control of movement sequences, may be a fundamental property of the basal ganglia. Motor disorders of the basal ganglia, such as Parkinson's disease and Huntington's disease, are associated with a profound loss of the ability to organize and execute sequences of movement. Furthermore, cognitive disorders of the basal ganglia such as the uncontrollable repetition of spoken words in Tourette's syndrome and the tormenting habits and thoughts of obsessive compulsive disorder suggest that sequential control mechanisms may be a fundamental property of the basal ganglia. In this project, the correlates and properties of single neurons related to instinctive, stereotyped sequences of behavioral actions will be studied. The long term goals of this project are designed to answer the following questions: How does the brain and in particular, the basal ganglia coordinate behavioral sequences? Are there basic principals for sequential organization? What are the computational properties of sequence-related neuronal assemblies in the basal ganglia? A key hypothesis to be tested in this study is that neuronal activity of a subset of cells in the basal ganglia will be related to movements within the context of rulegoverned behavioral sequences and not related to these movements when they occur on their own or in irregular, less organized sets of movements. Previous experiments have shown that rats exhibit highly structured (i.e., syntactical) sequences of grooming bouts that follow strict rules for their temporal organization and that these syntactical sequences are disrupted by damage to the basal ganglia. Rats also execute comparable grooming movements in isolation and in other randomly organized patterns of movements. Our method will be to record and compare the activity of single neurons in rats during both syntactical and non-syntactical grooming sequences. It is anticipated that neuronal activity will be preferentially linked to movements in the context of stereotyped syntactical sequences. We will evaluate the anatomical location of neurons related to grooming movements to test the idea that the functional organization is related to the proposed cortico-striatal loops in the basal ganglia. We will evaluate the hypothesis that neostriatal neurons mediate sequences by modulating sensorimotor responsiveness. Finally, we will test the idea that Dl dopamine receptor activation will enhance neuronal activity related to sequential movements and the dopaminergic lesions will produce the opposite effect. It is hoped that new information about the neuronal network properties related to the organization of behavioral sequences will lead to a better understanding of the pathophysiology of basal ganglia diseases and eventually contribute to better treatments for these brain disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: COGENT TO SUPPORT CLINICAL RESEARCH AT STANFORD Principal Investigator & Institution: Schatzberg, Alan F.; Professor and Chair; Psychiatry and Behavioral Sci; Stanford University Stanford, Ca 94305

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Timing: Fiscal Year 2001; Project Start 01-SEP-2000; Project End 31-AUG-2004 Summary: (Adapted from the Applicants Abstracts): This is an application for four years of CoGent funding to support 7 NIMH-funded R01's led by six PI's in the Departments of Psychiatry and Behavioral Sciences of Psychology at Stanford University. The R01's focus on a number of disorders - major depression with and without psychotic features, obsessive compulsive disorder, post-traumatic stress disorder, fragile X and other neurogenetic syndromes, and schizophrenia. This CoGent will increase the efficiency of the approved research of each of the studies, expand their scope, and allow for significant cross study collaborations. It consists of 3 cores - Recruitment, Statistics and Data Management, and Neuroimaging. The Recruitment Core will be located across three sites (two in Palo Alto and one in San Francisco) to increase recruitment of subjects. The San Francisco site will provide greater numbers of ethnic minority subjects for the Base Grants. The Core will facilitate subjects participating in more than one study. The Statistic and Data Management Core will assist in developing methods that can be used across studies for accessing longitudinal course and outcome (e.g. random regression models), response in randomized clinical trials (e.g. Reciever Operating Characteristics Curve Methodology), and the relative contributions of multiple risk factors. The Neuroimaging Core will offer prestudy exposure to a simulator and provide for additional scan time. A major feature of this CoGent is the application of fMRI across different populations being studied in the Base Grants. Several of the studies already use fMRI to study affect and cognition in specific disorders - e.g., schizophrenia, nonpsychotic and psychotic major depression, social phobia, fragile X, etc. The CoGent will permit utilization of standard fMRI experiments in these patient groups that will allow comparisons to be made across projects - e.g., hallucinating schizophrenic patients with hallucinating psychotic depressives. In two studies, the use of fMRI will significantly enhance the research design by exploring the specific effects of treatment on brain function. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: COGNITIVE THERAPY FOR OBSESSIVE-COMPULSIVE DISORDER Principal Investigator & Institution: Wilson, Kimberly A.; Psychology; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, Nc 27599 Timing: Fiscal Year 2001; Project Start 20-FEB-2001 Summary: Given the limitations of current treatments for obsessive-compulsive disorder (OCD), identification of alternative therapies is warranted. The primary aim of the present study will be to provide a test of the efficacy of cognitive therapy (CT) for obsessive-compulsive disorder (OCD). As a secondary goal, some of the mechanisms by which that treatment works will be explored. Three questions will be investigated: (a) Does participation in individual CT result in a clinically significant reduction of obsessive-compulsive symptoms?: (b) Do cognitive strategies exert a specific effect on target compulsions or is the impact more generalized?; and (c) Does depth of emotional experiencing facilitate successful sessions and outcome? To examine these questions, a multiple baseline across behaviors design will be used in which six participants with OCD will undergo standardized CT for 18 sessions. Over the course of treatment, participants will complete weekly batteries that measure OCD symptom severity and important cognitive domains (e.g., responsibility, perfectionism). They will also complete daily diaries of target symptoms including avoidance as well as time spent on and distress, related to specified obsessions and compulsions. Session videotapes will be coded for degree of within-session depth of experiencing. Analyses will include

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hierarchical linear modeling and exploration of graphical trends to address the objectives stated above. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: COGNITIVE THERAPY FOR PERSONALITY DISORDERS Principal Investigator & Institution: Hayes, Adele M.; Associate Professor; Psychology; University of Miami Coral Gables University Sta Coral Gables, Fl 33124 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2005 Summary: (provided by applicant): The Cluster C personality disorders (obsessivecompulsive, avoidant, and dependent) are the most prevalent personality disorders (PDs) in outpatient samples. These PDs are highly comorbid with mood and anxiety disorders. Patients with comorbid PD and Axis I disorders present with more severe and chronic symptom profiles, and they do not respond well to psychotherapy or pharmacotherapy. It is particularly difficult to establish a therapeutic alliance, a welldocumented predictor of treatment outcome, and treatment retention and compliance are often compromised. Given the prevalence of Cluster C PDs and their significant impact on psychosocial functioning, treatment response, and health care utilization, it is surprising that little attention has been paid to treatment development for this population. Cognitive therapy has been demonstrated to be an effective treatment across a number of Axis I disorders and recently has been extended to PDs. In a sample of patients with obsessive-compulsive (OCPD) and avoidant (AVPD) PDs, the first open trial of cognitive therapy for PDs (CT-PD) demonstrated significant improvements in personality symptoms, as well as in symptoms of depression and anxiety. Because the therapy is in early stages of development, general principles and guidelines for treatment of PDs are provided, but there are few specific details on how to treat OCPD and AVPD. This lack of specificity limits the extent to which the manual can be used to conduct larger scale clinical trials outside of the Center for Cognitive Therapy, where the manual was developed. The goal of this R-21 treatment development research is to identify active ingredients of the therapy and to use this process research to improve the specificity of the manual. CT-PD is thought to have its effects by exposing patients to corrective information challenging existing personality patterns, identifying the historical roots of these patterns, and providing exercises to facilitate generalization. The proposed study will examine these interventions as predictors of three hypothesized precursors of change: turbulence in defensiveness and avoidance (protection), the therapeutic alliance, and in-session affect. Growth curve modeling will be used to examine sequencing and timing of therapist interventions and relations between these interventions and the hypothesized precursors of change, which will then be examined as predictors of symptom reduction. Quality of therapeutic alliance in early sessions will be examined as a predictor of treatment retention. With this information, sections of the treatment manual on OCPD and AVPD can be refined, strategies to facilitate therapeutic alliance and symptom change can be specified, and the refined manual can be used in future proposals examining treatment efficacy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: COGNITIVE THERAPY IN OBSESSSIVE-COMPULSIVE DISORDER Principal Investigator & Institution: Wilhelm, Sabine; Assistant Professor; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2001; Project Start 15-JUL-2000; Project End 30-JUN-2003

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Summary: Obsessive-Compulsive Disorder (OCD) is a prevalent and often chronic disorder that is currently treated with pharmacological and psychological approaches. Exposure combined with response prevention (ERP) is presently considered the psychological treatment of choice. However, many patients refuse, drop out of or are unresponsive to pharmacotherapy or ERP. Many patients never engage in treatment or experience significant impairment even after treatment. Further, ERP may be less acceptable to therapists and to managed care settings. Thus, additional interventions for the treatment of OCD that improve outcome are needed. Recent studies suggest that cognitive treatment (CT) for OCD is at least as effective as exposure and response prevention. Moreover, cognitive approaches may be less stressful and have lower refusal rates than intensive forms of exposure or pharmacotherapy. CT also appears to help patients with symptoms that do not benefit from standard treatment. Finally, CT may be more acceptable to therapists and health care settings. This proposal seeks funds to develop, systemize and pilot test a cognitive treatment for patients suffering from OCD based mainly on Beck's methods. This treatment is derived from a theoretical model of cognitive aspects and effects on OCD symptoms and from empirical evidence regarding interpretation of intrusions and beliefs found in patients with OCD. We propose to fully develop a treatment manual, and accompanying therapist adherence and competency measures. After the treatment development phase, we will apply cognitive therapy of three different durations to OCD patients to determine which format is clinically most useful. In the final phase, we will collect pilot data on the best version of the therapy in comparison to a wait-list control. We will investigate treatment effects on different cognitive domains, specific OCD symptoms, mood state and functioning. The effect size of cognitive therapy for a primary outcome variable, the Yale-Brown Obsessive Compulsive Scale and response rate of treated subjects will be determined, preparatory to a larger scale randomized controlled trial, if this is indicated. Using a combined sample of 30 patients we will study the influence of a small number of possible predictors of posttest outcome. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: COLLABORATIVE LONGITUDINAL STUDY OF PERSONALITY DISORDER Principal Investigator & Institution: Shea, M T.; Associate Professor; Psychiatry and Human Behavior; Brown University Providence, Ri 02912 Timing: Fiscal Year 2001; Project Start 01-MAR-1996; Project End 31-MAY-2005 Summary: (APPLICANT'S ABSTRACT): The overall aim of this study is to provide a comprehensive picture of the course and outcome of four specific personality disorders (PDs): schizotypal (STPD), borderline (BPD), avoidant (AVPD), and obsessivecompulsive (OCPD). The present application continues a multi-site collaborative effort to follow a carefully diagnosed sample of 668 subjects having either these representative PDs or major depressive disorder (MDD) (controls) for the period from 3 to a maximum of 6 years after recruitment. Sixty new minority subjects will be recruited and followed for at least 2 years. Using a prospective, longitudinal, repeated measures design, we will develop the same basic knowledge about course and outcome for the PDs that has previously resulted from similar investigations of affective and anxiety disorders, thus addressing an important gap in our knowledge. The extended period of follow-up is essential to discern clinically meaningful descriptions of course and outcome and their determinants. The sample is large enough and sufficiently diverse demographically to attain a unique array of results generalizable to most clinical settings. To accomplish our overall aim, we propose three approaches: I. descriptive, II. predictive, and III.

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validating. The descriptive approach will provide data on diagnostic stability of PDs, on presence and course of comorbid Axis I disorders, on persistence of functional impairment, and on utilization of health care resources that allow comparison between the PDs and to similar data on Axis I disorders. The predictive approach will identify clinically meaningful determinants of prognosis within and across PDs. The validating approach will examine the homogeneity of descriptive and longitudinal features for the PDs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: COLLABORATIVE LONGITUDINAL STUDY OF PERSONALITY DISORDER Principal Investigator & Institution: Gunderson, John G.; Professor; Mc Lean Hospital (Belmont, Ma) Belmont, Ma 02478 Timing: Fiscal Year 2001; Project Start 01-MAR-1996; Project End 31-MAY-2005 Summary: APPLICANT'S ABSTRACT): This application is a revision of an application for 5 years continuation that was submitted in 1999. At that time a one year extension was awarded; this application is for four years. The overall aim of this study is to provide a comprehensive picture of the course and outcome of four specific personality disorders (PDs): schizotypal (STPD), borderline (BPD), avoidant (AVPD), and obsessivecompulsive (OCPD). The present application continues a multi-site collaborative effort to follow a carefully diagnosed sample of 668 subjects having either these representative PDs or major depressive disorder (MDD) (controls) for the period from 3 to a maximum of 6 years after recruitment. Sixty new minority subjects will be recruited and followed for at least 2 years. Using a prospective, longitudinal, repeated measures design, we will develop the same basic knowledge about course and outcome for the PDs that has previously resulted from similar investigations of affective and anxiety disorders, thus addressing an important gap in our knowledge. The extended period of follow-up is essential to discern clinically meaningful descriptions of course and outcome and their determinants. The sample is large enough and sufficiently diverse demographically to attain a unique array of results generalizable to most clinical settings. To accomplish our overall aim, we propose three approaches: I. descriptive, II. predictive, and III. validating. The descriptive approach will provide data on diagnostic stability of PDs, on presence and course of comorbid Axis I disorders, on persistence of functional impairment, and on utilization of health care resources that allow comparison between the PDs and to similar data on Axis I disorders. The predictive approach will identify clinically meaningful determinants of prognosis within and across PDs. The validating approach will examine the homogeneity of descriptive and longitudinal features for the PDs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: COLLABORATIVE LONGITUDINAL STUDY OF PERSONALITY DISORDER Principal Investigator & Institution: Morey, Leslie C.; Professor; Psychology; Texas A&M University System College Station, Tx 778433578 Timing: Fiscal Year 2001; Project Start 01-MAR-1996; Project End 31-MAY-2005 Summary: (Adapted from Applicant's Abstract) The overall aim of this study is to provide a comprehensive picture of the course and outcome of four specific personality disorders (PDs): schizotypal (STPD), borderline (BPI), avoidant (AVPD), and obsessivecompulsive (OCPD). The present proposal continues a multi-site collaborative effort to

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follow a carefully diagnosed sample of 668 subjects having either these representative PDs or major depressive disorder (MDD) (controls) for the period from 2 to a minimum of 6 years after recruitment. Using a prospective, longitudinal, repeated measures design, we will develop the same basic knowledge about course and outcome for the PDs that has previously resulted from similar investigations of affective and anxiety disorders, thus addressing an important gap in our knowledge. The extended period of follow-up is essential to discern clinically meaningful descriptions of course and outcome and their determinants. The sample is large enough and sufficiently diverse demographically to attain a unique array of results generalized to most clinical settings. To accomplish our overall aim, we propose three approaches I. Descriptive, II. Predictive, and III. Validating. The descriptive approach will provide data on diagnostic stability of PDs, on presence and course of comorbid Axis I disorders, on persistence of functional impairment, and on utilization of health care resources that allow comparison between the PDs and similar data on Axis I disorders. The predictive approach will identify clinically meaningful determinants of prognosis within and across PDs. The validating approach will examine the homogeneity of descriptive and longitudinal features for the PDs, as defined by the DSM system, and how this compares with alternative schemes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: COLLABORATIVE OCD GENETICS STUDY Principal Investigator & Institution: Nestadt, Gerald; Associate Professor; Psychiatry and Behavioral Scis; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2001; Project Start 01-JUN-1995; Project End 31-MAY-2006 Summary: The aim of this study is to identify susceptibility genes for OCD. We propose to recruit a sample of 350 pairs of siblings each with a strict DSM-IV diagnosis of OCD augmented with 200 extended pedigree families. To accomplish this, we have organized a group of six collaborating academic centers, each with rich clinical populations and research experience studying this condition. These centers are: Johns Hopkins University, the National Institute of Mental Health, Harvard University, Brown University, Columbia University, and the University of California at Los Angeles. The phenotypic assessments will be thorough and ensure comparability of the clinical information across all centers. There will be an emphasis on descriptive clinical material because we recognize both the importance of an accurate classification of the phenotype and-the need to explore potential homogeneous subclasses within the disorder which could facilitate the discovery of relevant genes. A genome-wide scan at ten centimorgan intervals will be conducted. Based on the results of linkage analyses, the more promising chromosomal regions will be investigated further. Materials will be made accessible to the public. The discovery of the genetic etiology of OCD should foster understanding of the pathophysiology and consequently improve the treatment and the lives of our patients. This goal is both appropriate and attainable. It is appropriate in that although we have made strides in our treatments, we continue to see patients in our clinics for whom treatments are ineffective and whose lives are substantially compromised. It is attainable because we have strong evidence at our disposal that OCD is a familial condition and molecular genetic methods are sufficiently advanced to provide the methods to detect the responsible genes even in conditions which have a complex pattern of inheritance and which may exhibit genetic heterogeneity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: COMPULSIVE FOOD-SEEKING & FOOD MOTIVATION IN PWS Principal Investigator & Institution: Thompson, Travis I.; Director; None; University of Kansas Medical Center Msn 1039 Kansas City, Ks 66160 Timing: Fiscal Year 2001; Project Start 26-APR-2001; Project End 31-MAR-2006 Summary: Excessive eating and the health and social problems resulting from it are the most serious problems associated with PWS. Despite the seemingly uncontrollable aspect of food related issues for people with PWS, laboratory studies of food choice reveal orderly and consistent food preferences in this population. Further, food rewards have been used successfully to teach speech articulation and physical exercise participation in people with PWS. During the current funding period, there was no detrimental impact of using food rewards and food-related cues on learning by people with PWS as compared to a population of comparably obese people, despite observing that food had greater motivational value for them. In addition, obsessive-compulsive symptoms in PWS subjects were negatively related to their performance on a sequential learning task. These findings have led us to hypothesize that food-related behavior problems in PWS are more likely to be related to obsessive-compulsive symptoms associated with PWS rather than the inflated motivational value of food. In the proposed research, adolescents and adults with PWS, a control group matched for MA and CA, and children, adolescents and adults with obsessive-compulsive disorder (OCD) will be evaluated. First, we propose to test the hypothesis that obsessive-compulsive symptoms in people with PWS and in people with OCD stem from altered frontal cortical processes. We will test this by comparing performance by these subjects on laboratory learning tasks known to involve orbitofrontal systems (e.g. Object Alternation), and tasks involving other frontal regions (e.g., extradimensional shift). Second, we will test whether perseverative errors on these tests are exacerbated exclusively in the PWS group when food related cues and rewards are used in these procedures. We also propose to examine how the altering the predictability of rewards associated exclusively with specific cues affects memory performance by people with PWS and OCD. We will then use functional magnetic resonance imaging to compare orbital frontal cortex (OFC) activation in people with PWS, people with OCD and controls. The major goal of the proposed research is to understand mechanisms underlying learning problems and food- related behavior problems in people with PWS. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CONTINUITY OF LIMBIC CIRCUIT THROUGH THE BASAL GANGLIA Principal Investigator & Institution: Haber, Suzanne N.; Anatomy and Neurobiology; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2003; Project Start 30-SEP-1989; Project End 31-MAR-2008 Summary: (provided by applicant): Mental disorders, including schizophrenia, obsessive compulsive disorder (OCD) and drug addiction are linked to pathology in the prefrontal cortico-ventral striatal-thalamic circuit by imaging studies, post mortem anatomical studies, and basic research. Not only do these illnesses have a common circuitry, but they all emerge relatively early in life, primarily during adolescence or young adulthood. Anatomical, physiological and pharmacological studies in this circuit have been central in gaining insight into the mechanisms underlying mental health disorders. The structures involved include the prefrontal cortex, the ventral striatum (VS), the ventral pallidum/substantia nigra, pars reticulata (VP/SNr), and the medial dorsal N. of the thalamus (MD), which links the circuit back to cortex. During the

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previous funding period we: 1. defined the territory of the VS in primates, 2. identified important and unique cellular features of the VS, including BCL-2 positive cells and newly formed cells from the subventricular zone, and 3. identified the afferent connections to the midbrain dopamine. We also demonstrated a mechanism by which the limbic component of the basal ganglia impacts on other basal ganglia circuits through striato-nigro-striatal pathways. Finally, place of the thalamus in cortical regulation emphasizes newer concepts in control of cortico-cortical activity through its complex connections. We showed that an integrative network exists for the dorsal basal ganglia through its thalamic projections to different cortical layers and through a nonreciprocal cortico-thalamic projection. The general hypothesis of this proposal is that the combination of the impact of the ventral BG thalamocortico-thalamic network several cortical areas along with the unique cellular features of the ventral striaturn place this circuit in a position to be particularly vulnerable during adolescence. The experiments proposed here will test this hypothesis by: 1. delineating the thalamo-cortical network to determine how pathways through the ventral BG circuit can both reinforce its own loop and also impact on other cortical areas and BG circuits; 2. characterize bcl-2-positive neurons and newly formed cells and determine whether the unique cellular characteristics of the VS differ during adolescence, and whether they are particularly vulnerable to stimulation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CORE--CLINICAL Principal Investigator & Institution: King, Robert; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2001 Summary: (Adapted from applicant's abstract): The Clinical Core will complete the Core Assessment Battery on the initial group of 377 subjects recruited through the previous funding cycle of the program project and recruit a new group of Tourette's syndrome (TS), obsessive-compulsive disorder (OCD), and attention deficit hyperactivity disorder (ADHD) subjects and matched community controls to participate in the proposed genetic, in vivo neuroimaging, neurobiological mechanisms, and treatment studies. To this end the core will develop rosters of eligible TS, OCD, and ADHD cases and controls, using clinical, community, and advocacy group resources, and will implement and monitor a Revised Minority Outreach Program to ensure optimal participation of women and minorities. The Clinical Core also has the responsibility to maintain and administer a Core Assessment Battery (CAB) for all subjects. A key element of this task is to train and monitor assessors in the reliable administration of the CAB. After ensuring the accuracy and completeness of the data acquired, the Clinical Core will transfer all data obtained to the Data Analytic Core for data entry. The core is also charged to ensure adherence of clinical studies to protocol designs and compliance with regulations involving human subjects. Finally, the investigators in the core will analyze data pertaining to the phenomenology and natural history of TS, OCD, and ADHD to refine clinical phenotypes and assessment procedures. These aims will be achieved through weekly meetings of the core and the daily efforts of the core personnel. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CRF-TYPE-2 RECEPTOR ANTAGONISTS FOR ANXIETY Principal Investigator & Institution: Gogas, Kathleen R.; Principle Scientist; Neurocrine Biosciences, Inc. 10555 Science Center Dr San Diego, Ca 921211100

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Timing: Fiscal Year 2002; Project Start 14-JAN-2002; Project End 13-JUL-2002 Summary: (provided by applicant): Since the CRF2 receptor was cloned in 1995, relatively little has been learned about its functional biology due primarily to the lack of pharmacological tools. Anatomical distribution data had suggested that the CRF2 receptor could be involved in feeding behaviors, which led to the idea that an antagonist to this receptor could have utility in treating eating disorders like anorexia nervosa. Recently, however, a selective peptide antagonist (antisauvagine-30) and agonist (urocortin II) have become available. Preliminary data obtained with antisauvagine-30 and urocortin II verified the importance of the CRF2 receptor in anorectic behavior, but the antisauvagine-30 (ASV-30) data also suggested that the CRF2 receptor may be involved in emotional behavior and anxiety. Thus, the potential therapeutic market for a CRF2 receptor antagonist could include a much broader spectrum of emotional disorders than anorexia nervosa. Therefore, we have proposed to investigate the possibility that the CRF2 receptor plays a role in anxious behavior, using ASV-30 and urocortin II as pharmacological tools. In anticipation of a positive finding, we have also proposed to begin the process of identifying a selective, high affinity, orally available CRF2 antagonist that could be used not only for the treatment of anorexia nervosa, but also for the treatment of anxiety disorders. Therefore, Phase I is focused: 1) on biological proof of principle for the role of CRF2 receptors in anxiety, and 2) on the initial identification of a high affinity CRF2 antagonist. Phase II would follow up with the actual development of such an antagonist, fine-tuning for selectivity, oral bioavailability and safety. PROPOSED COMMERCIAL APPLICATION: A small molecule CRF2 receptor antagonist could represent an anti?anxiety therapeutic with a novel mechanism of action and the potential to provide an improved efficacy and side effect profile in comparison to available therapeutics. Anxiety disorders are the most common form of mental illness in the United States, with an estimated one year prevalence of 16.4%, and an estimated cost of $993/year/person (USDHHS, et al., 1999). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DEEP BRAIN STIMULATION FOR REFRACTORY OBSESSIVE COMPULSIVE DISORDER Principal Investigator & Institution: Curtis, George C.; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: DISORDERS

EARLY

INTERVENTION

FOR

OBSESSIVE

COMPULSIVE

Principal Investigator & Institution: Zucker, Bonnie G.; Psychology; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2001; Project Start 01-SEP-2001 Summary: (provided by applicant): Although obsessive-compulsive disorder (OCD) affects only about 2.5-3 percent of the population, individuals with subclinical obsessive-compulsive symptomatology experience increased levels of distress and comorbidity than those with a lesser degree or absence of such symptoms. Additionally, it is hypothesized that people with subclinical OCD are at increased risk for developing OCD than those without subclinical symptomatology. However, there has been very little research on the transition from subclinical to clinical OCD. Thus the goals for this

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research program are two-fold: 1) The first aim of this study is to investigate whether a one-day long cognitive behavioral intervention is effective for reducing long-term distress and severity related to both obsessive-compulsive and comorbid psychopathology symptomatology, as compared to a no-treatment control group. 2) Although there is very little data on incidence of new cases of OCD from a subclinical population, the second purpose of this study is to see if the intervention is effective in offsetting new cases of OCD, as compared to the control group. Both the treatment and control groups will be followed for a year; data from the control group will contribute to the scant body of literature on one-year OCD incidence from a subclinical population. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EFFECTIVENESS OF MULTI-DRUG TREATMENTS IN TOURETTE'S Principal Investigator & Institution: Gilbert, Donald L.; Children's Hospital Med Ctr (Cincinnati) 3333 Burnet Ave Cincinnati, Oh 45229 Timing: Fiscal Year 2001; Project Start 15-AUG-2001; Project End 31-JUL-2006 Summary: The purpose of this K23 proposal is to prepare the candidate to become an independent investigator, able to design, acquire funding for, and perform valid clinical trials in children with co-occurring neurologic and psychiatric disorders. The candidate proposes a unique and well- integrated combination of educational experiences: 1) mentorship with established clinical trials researchers in psychiatry, neurology, and outcomes research; and 2) a rigorous master's training program in statistics and research design, with 30 hours of classroom time per month over 18 months. The candidate proposes to implement the lessons learned in a clinical effectiveness trial of multi-drug treatments in children and adolescents with Tourette's Syndrome, a paradigm disorder of co-occurring neurologic and psychiatric symptoms. Tourette's Syndrome is a neuropsychiatric disorder characterized by greater than one year of motor and vocal tics that are functionally or socially disturbing. Children and adolescents frequently have multiple co-occurring neuropsychiatric diagnoses and are treated with combinations of medications that have never been tested together. Current clinical research typically involves efficacy studies of monotherapy that may have limited clinical relevance. The research proposal of this K award includes a randomized controlled clinical effectiveness study of a dopamine agonist, pergolide, allowing for concurrent treatment of comorbid disorders. The primary hypothesis is that treatment with pergolide will be associated with significant tic suppression, independent of concurrent treatment for OCD or ADHD. The study will have the power to determine whether the presence of treated co-morbid OCD or ADHD accounts for significant variance in the change in tic symptoms on medication. An additional focus of the grant will be developing measures of health care utilization and costs in this disorder and determining their relationship to the presence of absence of effective symptom management. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ERROR-RELATED BRAIN ACTIVITY AND PEDIATRIC ANXIETY Principal Investigator & Institution: Hajcak, Greg; Psychology; University of Delaware Newark, De 19716 Timing: Fiscal Year 2003; Project Start 16-JUL-2003; Project End 15-JUL-2006 Summary: (provided by applicant): This research will integrate developmental psychophysiology and psychopathology by investigating error-related brain activity in pediatric obsessive-compulsive disorder (OCD) and trichotillomania (TTM) both before and after cognitive-behavioral intervention. The error-related negativity (ERN) is an

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Obsessive Compulsive Disorder

event-related brain potential (ERP) that has been associated with response monitoring and error detection. The ERN has been source-localized to the anterior cingulate cortex (ACC), which is part of the hyperactive fronto-striatal-thamalic circuitry in OCD (Stein, 2000). Thus, an enhanced ERN may serve as a marker of ACC hyperactivity relevant to the pathophysiology of OCD. Previous research has found ERN magnitude to be significantly correlated with symptom severity in a group of adult patients with OCD (Gerhing et al., 2000). The current research extends previous studies to pediatric populations, and includes pediatric TTM and pediatric controls. There is controversy about whether or not TTM is part of the OCD spectrum disorders, and the current study will provide psychophysiological data that may help differentiate these disorders. It is hypothesized that pediatric OCD patients will show enhanced error-related brain activity at protreatment, relative to both pediatric TTM patients and pediatric controls. Pediatric TTM patients are not expected to differ from pediatric controls with respect to error-related brain activity, supporting the notion that TTM is not simply a variant of OCD. Finally, the current study will also investigate the ERN after pediatric patients with OCD and TTM complete a course of CBT. It is hypothesized that only the errorrelated brain activity in pediatric OCD will change over the course of CBT reflecting the post-treatment alteration in the fronto-striatal-thalamic circuitry that underlies OCD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: FAMILY BASED TREATMENT OF EARLY CHILDHOOD OCD Principal Investigator & Institution: Leonard, Henrietta L.; Professor; Rhode Island Hospital (Providence, Ri) Providence, Ri 02903 Timing: Fiscal Year 2002; Project Start 15-MAR-2002; Project End 28-FEB-2005 Summary: (provided by applicant): Obsessive Compulsive Disorder (OCD) affects approximately 1 in 200 children and the onset of this disorder in childhood is a significant predictor of adult morbidity. To date, psychotherapy trials for youths with OCD have been designed for children 8 years and older and have been based on ageappropriate adaptations of the individual cognitive-behavioral treatment model found to be effective with adults. While preliminary evidence supports the efficacy of this approach during late childhood and adolescence, neither individual treatment nor cognitive therapy is developmentally appropriate options for the early childhood years. To date, no psychotherapy trials have focused specifically on this early childhood period. There are a number of unique features about early childhood onset OCD including developmental stage, symptom picture, and embeddedness in the family that makes treatment considerations for this disorder different from adults, adolescents, or even older children. Family based treatments have been used for other childhood disorders, but not OCD. Interventions for early childhood onset OCD need to be designed to address both developmental considerations and children's strong embeddedness in their family context. The primary aim of the present proposal is to develop and evaluate a short-term, manualized, family-based treatment intervention for Obsessive Compulsive Disorder (OCD) during early childhood (age 5-8 years). This proposal is submitted as an R21 Exploratory/Developmental Grant for Psychosocial Treatment Research in response to (PA-00-094) Early Identification & Treatment of Mental Disorders in Children). This project is designed to be conducted in three stages 1) Development, 2) Pilot Study, and 3) Randomized Control Study. The Manual Development phase will include review by experts. The Pilot Study stage will assess the intervention protocol for feasibility using 6 children. Information and feedback will be used to prepare a revised treatment manual. Additionally, a relaxation Therapy Manual will be tested in a pilot study of 6 children to determine its acceptability as a control

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treatment for the randomized study. A randomized controlled trial of 30 children, to compare the CBT manual (N=15) to that of the control (Relaxation) manual (N=15), will be completed. At the end of the study, a final revised, comprehensive, manualized treatment protocol would be completed which could be tested in large efficacy and effectiveness studies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: FAMILY ENVIRONMENT AND CHILDHOOD OCD Principal Investigator & Institution: Roblek, Tami L.; None; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2003; Project Start 17-SEP-2003; Project End 16-SEP-2005 Summary: (provided by applicant): OCD is a significant mental health concern. The identification of potential risk factors that may contribute to the development, maintenance and exacerbation of OCD in children remains understudied. OCD affects one to three percent of children and adolescents. Recent research suggests that family contextual factors may be a particularly promising domain for understanding and treating OCD and related disorders. The goal of the proposed research is to gain an understanding of family environmental factors and parent-child interactions involved in childhood OCD. More specifically, the proposed research will explore specific familial environmental factors and interaction patterns that occur in families of children with OCD, non-OCD anxiety disorders and no diagnosis. In addition, within the OCD group, the specificity of observed interaction will be examined by comparison to parentunaffected sibling interaction. Ninety parent-child dyads (plus 20 siblings) will be assessed via self-report and behavioral observation methodology. The current study will enhance our knowledge of family contextual factors in childhood OCD and other anxiety disorders and aid in the development of prescriptive treatment and prevention approaches for these disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: FEAR AND THE ANXIETY DISORDERS: BRAIN AND BEHAVIOR Principal Investigator & Institution: Lang, Peter J.; Graduate Research Professor; Clinical & Health Psychology; University of Florida Gainesville, Fl 32611 Timing: Fiscal Year 2001; Project Start 01-JUL-1982; Project End 30-APR-2003 Summary: (Applicant's Abstract): The plan of experiments emphasizes basic research on emotion as a framework for comparative clinical studies of phobic and anxious patients. The guiding theory of emotion is derived from animal research on functional brain activity in states of appetitive and defensive motivation. Work by Davis, LeDoux, Fanselow and others has defined a subcortical fear circuit, including the sensory thalamus, amygdala, and periaqueductal central gray. The startle reflex, and autonomic reactivity, are augmented in fearful animals, and this effect depends on an intact fear circuit (e.g., lesions of the amygdala eliminate potentiation). Research conducted on this project has demonstrated a parallel startle potentiation and autonomic change in human beings in fear conditioning, fear imagery, and while attending to unpleasant pictures and auditory stimulation. Exaggerated startle reactions also characterized specific anxiety diagnoses, and may vary with generality of psychopathology. The new basic research examines conical and subcortical reactivity (including brain sites of the animal model) in humans, using both scalp and subdural electrophysiological recording and functional magnetic resonance imaging to determine if fearful and aversive stimuli occasion hypothesized regional patterns of brain activity. Standardized picture stimuli

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Obsessive Compulsive Disorder

(IAPS) and text evoked imagery, shown to reliably produce emotion related ANS and reflex responses, are presented to subjects in the magnet to determine if there are regional blood oxygen level differences between neutral, pleasant, and aversive stimuli, and how these effects are modulated by arousal. A parallel set of experiments will utilize the EEG to examine cortical responses (ERP and slow-wave) to these same stimuli. Subsequent EEG and fMRI studies will examine phobic subjects (volunteers selected from the normal population) while they view pictures of and/or mentally image, phobic and non-phobic objects. The new clinical research effort includes major anxiety patient assessment studies, using mental imagery and picture paradigms, and multi-measure psychophysiological recording. Comparative analyses are made among anxiety disorders. The sample includes simple and social phobia, panic, post-traumatic stress, obsessive- compulsive, and generalized anxiety disorders. It is planned that the new neural imaging techniques will be added to this clinical protocol, as procedures develop in the basic studies. Goals of the project are to sharpen psychophysiological distinctions between fear (as in phobia), a phasic defensive reaction to a specific stimulus, and anxiety (as in GAD), a more persistent tonic defensive set with components of inhibition and depression. and furthermore, to evaluate memorial, cognitive style, and temperament differences among anxiety disorders, to sharpen differential diagnosis and assess the significance of depressive co-morbidity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: FLUOXETINE AFTER WEIGHT RESTORATION IN ANOREXIA NERVOSA Principal Investigator & Institution: Kaplan, Allan S.; Uhn Toronto General Hospital 200 Elizabeth St, Ccrw1-800 Toronto, Timing: Fiscal Year 2001; Project Start 07-JUL-2000; Project End 30-JUN-2004 Summary: Anorexia Nervosa (AN) is a serious psychiatric disorder with substantial morbidity and a lifetime mortality arguably as high as that associated with any psychiatric illness. A major contributor to the poor prognosis of this illness is the high rate of relapse which follows successful initial treatment. Patients with AN often exhibit symptoms of other psychiatric disorders, such a major depression and obsessive compulsive disorder, which respond favourably to treatment with medication. It is surprising therefore that medication treatment for AN has been consistently unsuccessful. Virtually all of the controlled trials of medication have been conducted during the initial phase of treatment, when patients are underweight. It is possible that medications are of limited utility during that phase of illness because of physiological and neurochemical effects of starvation. Therefore, it may be useful to explore the utility of medication among patients with AN after initial treatment has reversed the acute effects of starvation. The goal of the current proposal is to determine whether the SSRI fluoxetine, compared to placebo, reduces the rate of relapse and enhances psychological and behavioural recovery following initial treatment for AN. In order to answer this question, a two-site (New York and Toronto), four-year collaborative R01 study is proposed. Eighty patients with AN who have successfully completed initial treatment in an inpatient or intensive outpatient program will be randomly assigned to receive fluoxetine or placebo for 12 months under double-blind conditions while receiving appropriate psychological treatment. Outcome will be assessed on the basis of maintenance of weight and reduction in psychopathological symptoms characteristic of AN. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: FLUOXETINE AFTER WEIGHT RESTORATION IN ANOREXIA NERVOSA Principal Investigator & Institution: Walsh, Bernard T.; Professor; New York State Psychiatric Institute 1051 Riverside Dr New York, Ny 10032 Timing: Fiscal Year 2001; Project Start 01-JUL-2000; Project End 30-JUN-2004 Summary: (Adapted from the Applicant's Abstract): Anorexia nervosa (AN) is a serious psychiatric disorder with substantial morbidity and a lifetime mortality arguably as high as that associated with any psychiatric illness. A major contributor to the poor prognosis of this illness is the high rate of relapse that follows successful initial treatment. Patients with AN often exhibit symptoms of other psychiatric disorders, such as major depression and obsessive compulsive disorder, which respond favorably to treatment with medication. It is surprising therefore that medication treatment for AN has been consistently unsuccessful. Virtually all of the controlled trials of medication have been conducted during the initial phase of treatment, when patients are underweight. It is possible that medications are of limited utility during the phase of illness because of the physiological and neurochemical effects of starvation. Therefore, it may be useful to explore the utility of medication among patients with AN after initial treatment has reversed the acute effects of starvation. The goal of the current application is to determine whether the SSRI fluoxetine, compared to placebo, reduces the rate of relapse and enhances psychological and behavioral recovery following initial treatment for AN. In order to answer this question, a two-site (New York and Toronto), four year collaborative R01 study is proposed. Eighty patients with AN who have successfully completed initial treatment in an inpatient or intensive outpatient program will be randomly assigned to receive fluoxetine or placebo for 12 months under double-blind conditions while receiving appropriate psychological treatment. Outcome will be assessed on the basis of maintenance of weight and reduction in psychopathological symptoms characteristic of AN. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CHILDREN

FLUVOXAMINE

THERAPY

OF

ANXIETY

DIOSRDERS

IN

Principal Investigator & Institution: Labellarte, Michael; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2001 Summary: Although anxiety disorders are relatively common in children & adolescents, there are no controlled studies that have demonstrated efficacy of any treatment, either pharmacologic or psychosocial, for children & adolescents with anxiety disorders. Fluvoxamine is an SSRI that is marketed in the US for the treatment of obsessive compulsive disorder (OCD) in adults. Fluvoxamine has been used extensively throughout the world to treat a variety of anxiety & mood disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: FMRI STUDIES OF IMPULSE CONTROL IN CHILDHOOD DISORDERS Principal Investigator & Institution: Peterson, Bradley S.; House Jamison Assistant Professor; New York State Psychiatric Institute 1051 Riverside Dr New York, Ny 10032 Timing: Fiscal Year 2001; Project Start 01-AUG-1999; Project End 31-JUL-2003

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Obsessive Compulsive Disorder

Summary: The overall objective of this proposal is to use functional MR brain imaging (fMRI) to better understand the neural circuits that contribute to problems with impulse control in Tourette's syndrome, Obsessive-Compulsive Disorder (OCD), and Attention Deficit Hyperactivity Disorder (ADHD). Clinical experience has shown that children who suffer from almost any serious developmental disability suffer most not from their primary diagnostic symptoms, but from their difficulties with impulse control, hyperactivity, inattention, and response inhibition. These associated problems cut across most diagnostic domains and are the most frequent cause for clinical referral, and by understanding dysfunction in this circuitry we will be better able to design and assess the effects of new therapeutics for these problems. We aim to understand better the neurobiology of these problems through the imaging of motor, attention, and inhibitory neural systems involved in impulse control in normal and developmentally disabled children. Our specific aims are: 1) To use fMRI to study the neural basis of impulse control in 80 normal children and adults (7-50 years old), and to compare the brain activity in these normal subjects with the brain activity in 80 TS, 40 OCD, and 40 ADHD subjects. 2) To study the functional connectivity of brain regions that subserve impulse control. 3) To show that task-related changes in fMRI signal can predict important behavioral measures in our models of impulse control. 4) To determine the effects that stimulant medications have on the activity of impulse control circuits in 40 children who have ADHD. 5) To develop and apply to the study of our models of impulse control new "event-related" fMRI task activation protocols in 40 normal and 40 matched TS children and adults. These studies should provide important new insights into the underlying neurobiological basis of each disorder. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: FOLLOW-UP STUDY OF OBSESSIVE COMPULSIVE DISORDER Principal Investigator & Institution: Rasmussen, Steven A.; Associate Professor; Butler Hospital (Providence, Ri) 345 Blackstone Blvd Providence, Ri 02906 Timing: Fiscal Year 2001; Project Start 09-APR-2001; Project End 31-MAR-2006 Summary: There have been significant advances over the last decade in our understanding of the epidemiology, etiology, and treatment of obsessive-compulsive disorder (OCD). Data from older studies suggests that the course of OCD is usually chronic. However, there are significant gaps in the literature regarding the long-term patterns of course and predictors of this disorder. We do not know whether certain subtypes of OCD have a more pernicious course than other subtypes. The impact of OCD on psychosocial functioning over time is another currently clinically relevant area that has not been examined in previous studies. The broad objective of this proposal is to develop a comprehensive picture of the longitudinal course and outcome of OCD using a prospective, longitudinal, observational design to follow 400 subjects with OCD over a period of three to five years. Specific aims are to: comprehensively describe the long-term patterns of course of OCD; identify clinically meaningful predictors of remission and relapse; prospectively describe the amount of psychiatric treatments received; assess the relationship between psychosocial function, quality of life and OC symptom severity over the follow-up period. Using a well-defined method developed by Keller and colleagues for observational studies of anxiety and depression, the study will evaluate 400 consecutive patients with OCD using DSM-IV criteria for the disorder over a three to five year follow-up period. Detailed information on symptom status and severity, functional impairment, quality of life, diagnostic Status and treatments received will be recorded systematically using instruments with proven reliability and validity at yearly intervals. This study will be the first comprehensive prospective

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observational study of the course of illness in OCD and will be the first study to prospectively determine remission and relapse rates according to DSM-IV criteria. It will provide important new information about longitudinal aspects of treatment and predictors of remission and relapse that will, in turn, help refine data supporting the existence of homogeneous subtypes in OCD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: FRONTOSTRIATAL DEVELOPMENT AND COGNITIVE CONTROL Principal Investigator & Institution: Casey, Betty J.; Professor; Psychiatry; Weill Medical College of Cornell Univ New York, Ny 10021 Timing: Fiscal Year 2001; Project Start 01-MAY-2001; Project End 30-APR-2006 Summary: One key feature of cognitive and behavioral development is the gradual ability to override one behavior in favor of another or to suppress attention to irrelevant information in favor of more relevant information. The proposed studies examine the normal development of this ability and its neural basis. Behavioral paradigms will be used that parametrically manipulate the degree of interfering, irrelevant information, thereby increasing the demands for overriding an attentional or behavioral response (i.e., cognitive control). The investigators will examine the structural and functional connectivity of brain systems including the prefrontal cortex and basal ganglia, assumed to play a role in cognitive control. They propose to use the following methods to address this issue: 1) structural magnetic resonance imaging (MRI) to examine morphometric changes in relevant brain structures; 2) diffusion tensor imaging to examine the extent of myelination of frontostriatal circuitry; and 3) functional MRI in conjunction with well defined cognitive paradigms to examine the functional development of neural systems involved in cognitive control. The investigators will use a cross lag design exploiting both cross-sectional and longitudinal information across the ages of 4 to 30. Further, to understand the neuromodulatory role of dopamine in this developmental process, known polymorphisms in genes that contribute to the neuromodulatory effects of dopamine will be examined via gene association studies. A number of such polymorphisms have been identified that occur relatively frequently in the general population. The investigators will collect DNA samples from the cheek cells of subjects. This DNA will be typed for variation at a particular gene and then correlated with behavioral performance using simple population-based statistical tests. The method is simple, noninvasive, reliable, fast and inexpensive relative to the neuroimaging studies. They will determine if measures of genetic variation predict performance on tasks of cognitive control or relate to measures of structural and functional brain development. This work promises to have significant implications at the behavioral, biological, and ultimately at the genetic level for developmental disorders that have as a core deficit, a problem overriding or suppressing inappropriate thoughts and behaviors like Attention Deficit-Hyperactivity Disorder, Obsessive Compulsive Disorder and Tourette syndrome. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: FUNCTIONAL MRI OF TASK INDEPENDENT PROCESSING Principal Investigator & Institution: Binder, Jeffrey R.; Professor; Medical College of Wisconsin Po Box26509 Milwaukee, Wi 532264801 Timing: Fiscal Year 2001; Project Start 01-APR-2001; Project End 31-MAR-2002 Summary: Task-induced decreases in cerebral blood flow are a frequent finding in functional brain imaging research but have not been adequately explained. Many of the

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Obsessive Compulsive Disorder

brain areas that typically show such decreases have also been implicated in semantic processing. One hypothesis accounting for both observations is that attentiondependent, unsolicited semantic processing occurs during conscious resting state and is interrupted by shifting of attention to non-semantic tasks. Non-semantic tasks thus produce decreases in neural activity in regions normally engaged in semantic processing during rest or "thinking"). The specific aims of this proposal are to test the main predications of this model using functional magnetic resonance imaging (fMRI) and behavioral measures of semantic processing capacity. First, the model predicts that changing the attentional demands, or difficulty, or a non-semantic task should produce correlated changes in task-induced signal decreases measured with fMRI. More importantly, these changes should be correlated with reductions in semantic processing capacity measured during the same task conditions. Specific Aim 1 is to test these predictions by correlating changes in semantic processing capacity and fMRI signal decreases during controlled manipulations of attentional load in non-semantic task. Second, the model predicts that semantic tasks should not cause fMRI signal decreases, as these tasks engage the same brain areas that are engaged in semantic processing during rest. Specific Aim 2 is to test this prediction by measuring fMRI signal decreases during controlled manipulations of semantic processing load while attentional load is held constant. If correct, the main hypotheses will provide a unifying account of disparate findings from functional imaging studies of semantic processing, an explanation for at least some task induced "deactivations," and much needed information about resting state brain activity that would be broadly applicable to the design and interpretation of functional imaging experiments. These data could also provide novel research approaches to neuropsychiatric conditions characterized by abnormal thought content, including schizophrenia, obsessive compulsive disorder, affective disorder, and autism. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENETIC INVESTIGATION OF AUTISM IN A FOUNDER POPULATION Principal Investigator & Institution: Mcinnes, L A.; Psychiatry; Mount Sinai School of Medicine of Nyu of New York University New York, Ny 10029 Timing: Fiscal Year 2003; Project Start 15-AUG-2003; Project End 30-APR-2007 Summary: (provided by applicant): Autism is a heritable neurodevelopmental disorder characterized by impairment in three domains including social interaction, communication and restricted repetitive and stereotyped patterns of behavior detectable before the age of three (American Psychiatric Association, 1994). Although the disorder is likely characterized by extensive genetic heterogeneity, certain traits such as language delay and types of repetitive behavior appear to segregate within families and may allow delineation of phenotypes with more homogeneous genetic determinants. In order to eliminate as much genetic heterogeneity as possible, we plan to investigate these endophenotypes, as well as autistic spectrum disorders, in the genetically isolated population of the Central Valley of Costa Rica. We will evaluate obsessive-compulsive symptoms, personality characteristics and language ability of first-degree family members to study genotype/phenotype correlations. Our goal is to perform a genomewide screen for autism susceptibility loci utilizing population genetic mapping methods in a sample of 175 trios; we also hope to fine-map loci discovered by other groups. In the process, we will examine the utility of recent multipoint methods of linkage disequilibrium analysis for the fine-mapping of disease loci using both microsatellites and single nucleotide polymorphisms.

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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENETIC MODELING OF PSYCHOPATHOLOGY Principal Investigator & Institution: Vieland, Veronica J.; Professor of Biostatistics, Psychiatry a; Prev Med & Environmental Hlth; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2001; Project Start 01-MAY-1997; Project End 30-APR-2002 Summary: (Adapted from applicant's abstract): This is a request for a Career Development Award. The purpose of this application is to ensure the applicant adequate time for research, necessary to the continued development of her career as an independent investigator in statistical genetics with psychiatric applications, as well as to provide additional clinical training. The candidate is an expert in the application of statistical methods in psychiatric research. From 1990-1995 she has been supported by a prior NIMH Career Development Award. During the time she has acquired a broad background in human and psychiatric genetics and developed her skills in her own area of expertise, and she has already made several fundamental contributions to the field of statistical methods in psychiatric research. She has recently been recruited to join the faculty of The College of Medicine at the University of Iowa which has an outstanding research program in psychiatry and a strong commitment to genetics research. The discovery of genetic mechanisms underlying psychiatric disorders can facilitate diagnosis and prevention, aid in the development of more effective interventions, and broaden understanding of the contributions of both nature and nurture to psychopathology. Enormous technologic advances in recent years have made sophisticated modeling of complex genetic disorders feasible in principle. However, what is available in theory is not always feasible in practice. A fundamental source of difficulty involves proper procedures for sampling (ascertainment of families) and proper mathematical treatment of sampling in data analysis. Unresolved sampling problems can make planning and executing a genetic study of a complex disorder extremely difficult. The proposed research will address major sampling issues for complex genetic analysis using both analytic mathematical approaches and simulation studies. The candidate maintains ongoing established collaborations with clinicians on genetic studies of panic disorder, autism, and obsessive-compulsive disorder. All theoretical work will be both guided by and applied to the analysis of data from these studies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GENETIC STUDIES IN MENTAL FUNCTION Principal Investigator & Institution: Karayiourgou, Maria; Rockefeller University New York, Ny 100216399 Timing: Fiscal Year 2001 Summary: We investigate the genetic causes of two of the major psychiatric disorders: Schizophrenia and Obsessive-Compulsive Disorder (OCD). Schizophrenia has been called "arguably the worst disease affecting mankind, even AIDS not excepted". The worldwide lifetime prevalence of the disorder is about 1% across diverse geographic, cultural, and socioeconomic categories. Obsessive-Compulsive Disorder is a neurobiological disorder which affects 2-3% of the population. Family, twin and adoption studies provide overwhelming but indirect evidence for a significant genetic contribution to the etiology of both disorders. Inheritance is not simple however and most likely involves a number of susceptibility genes and environmental influences. Our goals are: 1)to identify genes for both disorders; 2)to specify the function, and mode of

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Obsessive Compulsive Disorder

dysfunction, of the involved genes; 3)to define the genotypic and phenotypic heterogeneity of these disorders; and 4)to propose improved treatments for these disorders, based on our genetic findings. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENETICS OF ANOREXIA NERVOSA Principal Investigator & Institution: Brandt, Harry A.; St. Joseph Medical Center (Towson, Md) 7620 York Rd Towson, Md 21204 Timing: Fiscal Year 2002; Project Start 06-SEP-2002; Project End 31-JUL-2006 Summary: (provided by applicant): Anorexia nervosa (AN) is a chronic and often fatal disorder that affects 0.3% of women. There is no FDA-approved treatment, and the mortality rate is 5% per decade. In addition to environmental influence, family and twin studies demonstrate substantial heritability for AN. Because the etiology of this devastating illness is not known, we undertook a pilot study to examine its genetic underpinnings. With the support of a private foundation, our multicenter collaboration has collected 196 multiplex AN kindreds from 7 sites across North America and Europe. With a limited sample, this pilot study has produced four suggestive linkages from a genome-wide scan, one very close to genome-wide significance (Chromosome 1 at 70 cM, p - 0.0001; Chr. 1 at 202 cM, LOD = 3 46. p = 0.00003; Chr. 2 at 102 cM, LOD = 2.22: p = 0.00070; and Chr. 13 at 102 cM. LOD = 2.50; p = 0.00035) The first suggestive linkage results from a subset of the sample, namely individuals with the restricting subtype of AN. The other results were obtained by incorporating two covariates, drive-for-thinness from the Eating Disorders lnventory-2 and the total score from the Yale-Brown Obsessive Compulsive Scale, into covariate-based linkage analysis. Based on these very promising linkage findings, we believe genes underlying liability to AN can be mapped by augmenting the pilot sample. Thus support is requested for a multicenter effort to collect 400 affected relative pairs with AN. Over a five year period, the 11 collaborating groups (10 clinical, 1 analytic) will collect diagnostic and other phenotypic data and blood samples from 400 multiplex AN kindreds. The UNIVERSITY OF PITTSBURGH is one of these research groups. each of which is submitting a nearly identical application as a group of collaborating ROls. Microsatellites will be genotyped at H 10 cM intervals across the genome using all new families. Linkage analyses will be conducted by using diagnostic and phenotypic data to confirm suggestive linkages from the pilot study and to identify new genomic regions of interest. The diagnostic and genetic data and lymphoblastoid cell lines (derived from blood samples) will become part of a national archival resource for genetic studies of AN through the NIMH Genetics Initiative. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GENETICS OF MAJOR BEHAVIORAL DISORDER IN CHILDREN AND ADULTS--TOURETTE SYNDROME Principal Investigator & Institution: Pauls, David L.; Director and Professor; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2001 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: IMPROVING THE MEASUREMENT OF PSYCHOPATHOLOGY Principal Investigator & Institution: Woods, Carol M.; Psychology; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, Nc 27599 Timing: Fiscal Year 2002; Project Start 12-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): The purpose of this research is to improve measurement of psychopathology through the use of item response theory (IRT). IRT is a set of statistical models and techniques used to evaluate items and score questionnaires, interviews, rating scales, etc. IRT techniques are preferable to classical test theory methods (e.g., Cronbach's alpha, summed scores), because IRT models provide detailed information about items that: a) aids in the creation of short, but reliable instruments, b) produces indices of scale precision that vary for different people to better reflect individual differences, and c) allows for the computation of scores that account for heterogeneity of discrimination ability among the items. However, currently implemented IRT models often assume that the construct measured by the items is normally distributed in the population, which is untenable for psychopathology. IRT analyses based on a false assumption about the distribution of the latent construct likely produce misleading results. The first aim of the proposed study is to adapt existing IRT so that the distribution of a latent construct in the population is allowed to adopt nearly any shape. The new procedure and software will be tested with a computer simulation study, wherein the algorithm is applied to computer-generated data. The second aim of the proposed study is to apply the new technique to data from two self-report questionnaires on obsessive-compulsive disorder symptoms, thereby producing distributions of the latent constructs and properties of the items, which may suggest potential revisions to the measures. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: IMPROVING THE OUTCOME OF PATIENTS WITH OCD Principal Investigator & Institution: Simpson, Helen B.; Assistant Professor of Clinical Psycholo; Psychiatry; Columbia University Health Sciences New York, Ny 10032 Timing: Fiscal Year 2001; Project Start 07-JUL-2000; Project End 30-JUN-2005 Summary: Obsessive-compulsive disorder (OCD) is a disabling illness with a lifetime prevalence as high as 2-3 percent. This K23 application proposes a program of career development and research that will help the P.I. achieve her long-term goal: to improve the outcome of patients with OCD. The program will be carried out under the mentorship of Dr. Michael Liebowitz and in collaboration with Drs. Edna Foa, Marc Laruelle, and other preceptors (Drs. Donald Klein, Jean Endicott, David Pauls, Scott Rauch, Paul Greene, and Eva Petkova). The training program is designed so that the P.I. will: 1) develop expertise in the phenomenology and treatment of OCD (by receiving expert supervision in the evaluation and treatment of OCD patients, advanced training in psychopharmacological treatment and cognitive-behavioral therapy using exposure and ritual prevention (EX/RP), and specialized training in tic disorders); 2) acquire the skills and experiences needed by an independent clinical researcher (by coursework/supervision in research design, multivariate statistics, outcome measures, and ethics and by conducting several research projects, including a large clinical trial); and 3) be able to collaborate effectively with brain imaging experts (by learning about state-of-the-art imaging methods and helping to conduct an OCD brain imaging project using MRI and PET technology). The research component will consist of three complementary projects: 1) the assessment of residual clinical symptoms and of functional and neurocognitive impairments in a large sample of treated OCD patients; 2)

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Obsessive Compulsive Disorder

a randomized controlled trial to examine the efficacy of adjunctive EX/RP for augmenting serotonin reuptake inhibitors in OCD; and 3) the measurement of the serotonin transporter in OCD patients and normal controls (using a radiolabeled ligand and PET) to examine whether there are specific serotonergic abnormalities in the brains of OCD patients. The long-term goal of this work is to improve the outcome of patients with OCD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INDOLE ANALOGS AS NOVEL TREATMENTS FOR OCD Principal Investigator & Institution: Sard, Howard P.; Organix, Inc. 240 Salem St Woburn, Ma 01801 Timing: Fiscal Year 2002; Project Start 01-MAR-2002; Project End 31-AUG-2002 Summary: (provided by applicant): Obsessive Compulsive Disorder (OCD) is a serious mental illness that affects millions of people throughout the world. Existing therapies for OCD show limited efficacy, can possess troubling side effects, and often require long-term treatment. Discovery of a new treatment for OCD would have considerable scientific value and commercial value. The hallucinogen psilocybin has shown preliminary efficacy against OCD, however even if further research on this compound is positive, FDA approval for psilocybin could be problematic. In Phase One we propose to synthesize carefully selected psilocybin analogs. The pharmacology of these compounds will be evaluated both in vitro and in vivo. From this project we specifically aim to discover one or more psilocybin analogs showing efficacy in an animal model for OCD comparable to that of the existing therapies. Such a result will strongly support continuation in Phase Two. The long-term goal of this project is to discover new, improved treatments for OCD. PROPOSED COMMERCIAL APPLICATION: Discovery of a novel, improved therapy for obsessive compulsive disorder could alleviate suffering for many people worldwide and would have very substantial commercial potential. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: JUVENILE ONSET OCD AS A MEANINGFUL DEVELOPMENT SUBTYPE Principal Investigator & Institution: Geller, Daniel A.; Mc Lean Hospital (Belmont, Ma) Belmont, Ma 02478 Timing: Fiscal Year 2001; Project Start 01-MAY-1999; Project End 30-APR-2004 Summary: This application represents an integrated plan of research and training which will allow the Candidate to acquire the necessary skills to become independent as a clinical investigator. The Candidate has demonstrated a commitment towards the pursuit of clinical excellence and original research in the area of Obsessive Compulsive Disorder (OCD) in children and adolescents over many years, manifested by a highly reputed clinical program, small grant support and original scientific publications. The Candidate is seeking the support of a Mentored Clinical Scientist Development Award in order to undertake a comprehensive program of didactic and mentored training and clinical research using the proposed research plan as a vehicle for scientific development. The Candidate is in an outstanding environment for this purpose and has assembled a highly qualified group of consultants who are leaders in their field and who are dedicated to the Candidate's research career success. The scientific development plan proposed includes training in Clinical Research Methods in Child Psychiatry-20 percent, Clinical Research Methods in Adults with Obsessive

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Compulsive and Related Disorders-10 percent, and courses at the Harvard School of Public Health in epidemiology and biostatistics which comprise the Formal Didactic Training-10 percent. The Candidate's background, scientific biography, research objectives and career goals reveal a clear and constant trajectory and a coherent plan for a career studying OCD in the pediatric population. The rationale for the Candidate's proposed Research Plan-35 percent, derives from the premise that OCD is very likely a heterogeneous disorder and further, that an understanding of this etiologic heterogeneity is important, not only for clinical purposes, but also as a fundamental step in future neurobiological research. The Candidate contends, using his own work and the reviewed literature, that age at onset of OCD represents the most compelling variable to study to examine etiologic heterogeneity because OCD which begins in childhood differs in important ways from the adult-onset disorder. To this end, the Candidate proposes to test several competing hypotheses to determine whether the childhoodonset form of OCD is the same or different from adult-onset OCD by studying the clinical correlates and familial aggregation of psychiatric disorders in 100 juvenile OCD probands, 50 adult OCD probands with juvenile-onset OCD and 50 adult OCD probands with adult-onset OCD and their first degree relatives. By providing data that are independent from findings in the proband, family-genetic data provide a powerful method to investigate whether juvenile-onset OCD is a clinically meaningful subtype of OCD. The clinical, scientific, and public health relevance of confirming or refuting these hypotheses is discussed. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DISORDER

LINKAGE

&

ASSOCIATION

IN

OBSESSIVE-COMPULSIVE

Principal Investigator & Institution: Grados, Marco A.; Medical Director; Kennedy Krieger Research Institute, Inc. Baltimore, Md 21205 Timing: Fiscal Year 2002; Project Start 20-SEP-2002; Project End 31-AUG-2003 Summary: (provided by applicant): This application describes a 5-year training program of didactic study, research mentoring and research activities focusing on the genetics of childhood obsessive-compulsive disorder (OCD). The training program will allow the candidate to gain expertise in methods of genetic research in complex disorders, including linkage, association and bioinformatics. The long-term objective of the career development plan is to extend the candidate's expertise in psychiatric phenotyping, statistical genetics and bioinformatics. To accomplish this goal, research activities will use the resources of the Johns Hopkins Department of Psychiatry for the understanding of the OCD phenotype; the Hopkins School of Public Health and National Human Genome Research Institute for bioinformatics, statistical genetics and genetic epidemiology training; and the Hopkins Genetics Core Lab facility for genotyping. Preliminary work includes the candidate's previous experience in a NIMH-funded family study of OCD with adult probands and pilot feasibility data from OCD child proband families. The research design consists of 2-stage sampling and psychiatric interviews of 80 OCD child probands and 720 first-, second-degree relatives. Probands are recruited by consecutive nonprobability sampling to maximize their utility for linkage and segregation. Only non-sib relatives undergo screening for greater efficiency of phenotyping. The research plan components are: a) phenotypic characterization of childhood OCD; b) linkage using affected-relative pairs to 4 candidate gene regions (SLC6A4-serotonin transporter, COMT, MAOA, DRD4) using 3 SNP biallelic markers and 4 flanking microsatellite markers; c) complex segregation analysis to obtain the mode of transmission and major gene effect; d) family-based tests of linkage

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Obsessive Compulsive Disorder

disequilibrium using the 4 candidate gene alleles and; e) tests of genetic heterogeneity with the tic-related OCD subtype. Based on results from initial analyses and developing collaborations with other research groups future research projects, such as a genomewide screen of OCD, are considered. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MECHANISMS OF DOPAMINE & SEROTONIN IN TOURETTE SYNDROME Principal Investigator & Institution: Wong, Dean F.; Vice Chair for Research; Radiology; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2001; Project Start 01-APR-2001; Project End 31-MAR-2004 Summary: (Verbatim from the Applicant's Abstract) The mechanisms and significance of the dopaminergic and serotonergic neurotransmission systems in Tourette Syndrome (TS) have not been thoroughly investigated and explained. A more complete understanding of their roles in TS would lead to better selection of pharmacological treatments for these patients and provide insight into the pathophysiology of TS. This project will examine pre-, and post- and intrasynaptic dopamine neurotransmission DA transporter (DAT), D2 density (D2Bmax) and DA release (DArel), simultaneously in patients with TS. Serotonin abnormalities will be studied in patients with TS and obsessive-compulsive disorder (OCD), a co-morbid disease. Based on our prior neuroreceptor imaging experience with positron emission tomography (PET) in TS and other neuropsychiatric disorders, we hypothesized that DArel stimulated by an amphetamine challenge will be increased in TS and will correlate with the severity of symptoms (Aim 1). In Aim 2 we will investigate how the relationship between the pre-, post- and intrasynaptic measures of dopamine differ between patients with TS and normal controls. For example, we predict dopamine release and D2 dopamine receptors will both be increased in TS compared to normal subjects. There is a need to establish appropriate serotonin and dopamine/serotonin combinations in the treatment of TS. We hypothesize that there are abnormal serotonin receptors and transporters in TS subjects prior to treatment and that the differences will be most pronounced in subjects with symptoms of OCD. We will examine pre-synaptic serotonin transporters(SERT) and post-synaptic (5HT24R) in TS subjects with and without OCD and compare the results to controls with and without OCD (Aim 3). In Aim 4 we will explicitly examine the relationship of DArel together with the serotonergic measures to explore dopamine serotonin interactions in the same individual. The measurement of pre-, and post- and intrasynaptic dopaminergic parameters has never been performed simultaneously in the same TS subject. Serotonin 5HT24R and SERT have not been studied in same patients with TS and symptoms of OCD. We propose to carry out experiments using PET to establish a more complete understanding of the neurotransmission in TS. This will also help establish new ationales for improved therapeutics in TS. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MECHANISMS OF STREPTOCOCCAL/HOST INTERACTION Principal Investigator & Institution: Zabriskie, John; Rockefeller University New York, Ny 100216399 Timing: Fiscal Year 2001 Summary: We have now completed our studies on the nature of the nephritogenic protein using the sera and renal biopsies from patients with acute post streptococcal glomerulonephritis (APSGN). All nephritogenic strains produce a protein called

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nephritis plasmin binding protein (NPBP) which was isolated, sequenced and found to be identical with streptococcal proteinase or streptococcal pyrogenic exotoxin B (SPEB). Using antibodies prepared against recombinant SPEB, 65% of 20 APSGN biopsies were found to contain the antigen in the glomerulus while only 4% of 25 non APSGN biopsies were positive. None of the biopsies were positive for streptokinase, another streptococcal antigen possibly associated with APSGN. APSGN sera reacted preferentially with this antigen when compared to sera from patients with either rheumatic fever or uncomplicated streptococcal infections and normal controls. Furthermore, serial serum studies of APSGN patients revealed that while the titers decreased over one year they never returned to baseline values suggesting a possible protective effect against the known fact that recurrences of APSGN are extremely rare. A manuscript detailing these findings has been submitted to Kidney International. Studies involving the rheumatic fever marker D8/17 have proceeded along two areas of investigation. The first is concerned with the predictive role of the marker for disease susceptibility. Approximately 3,000 children ages 5-10 years who come from high risk areas of rheumatic fever in Mexico City have been tested for the marker. Seven percent of these unaffected children are positive for the marker. All children are being followed over time for the appearance of rheumatic fever. If our hypothesis is correct, only those positive for the D8/17 marker will be susceptible. The second area of investigation of the marker was unexpected. In collaboration with a group from Child Psychiatry at NIH under the direction of Dr. Sue Swedo, we have examined the presence or absence of this marker in a group of 23 children (and appropriate controls) with obsessive-compulsive disorders (OCD). In a double blind test the marker correctly identified ninety percent of the OCD patients compared to the expected 7% controls. In view of the known crossreactions between streptococcal antigens and caudate nucleus cells, these studies suggest that other brain-streptococcal cross reactive antigens may be involved in the OCD syndrome. A manuscript detailing these findings has been sent to the J. Child Psychaitry. Our more basic approach to the exact nature of the D8/17 antigen and caudate binding antigen in the sera of Sydenham's chorea are being pursued along two main lines of investigation. Concerning the D8/17 antigen our main problem in identifying this antigen has been the fact that the antibody is the IgM class. Thus nonspecific binding of other proteins has resulted in identification of a number of bands. Secondly, this antibody does recognize other antigens expressing a coil-coiled structure. We have recently isolated a IgG clone of the D8/17 antibody and hope this will have the same specificity as the IgM molecule. We are also using the chemiluminescence technique (quite sensitive) to further identify the putative antigen. Concerning the Sydenham's caudate antigen we are screening sera from these patients both on a cDNA library of human caudate as well as immunoblots of human and mouse caudate specimens. In this respect we have identified two bands of 82 and 66 Kda that appear promising. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MENTORED DEVELOPMENT AW

PATIENT-ORIENTED

RESEARCH

CAREER

Principal Investigator & Institution: Mathews, Carol A.; Obstetrics, Gynecology and Reproductive Sciences; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 94122 Timing: Fiscal Year 2001; Project Start 15-JUN-2000; Project End 31-AUG-2001 Summary: (Adapted from the applicant's abstract): The applicant's goal for this CAP award is to develop the multidisciplinary skills necessary to become expert in

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Obsessive Compulsive Disorder

integrating complex genetic and clinical information in order to more fully characterize complex genetic neuropsychiatric disorders. Her developmental plans include focused research aimed at integrating clinical and genetic studies, as well as a program of course work, research seminars, and structured mentoring. Her research agenda is aimed at characterizing TS and its associated comorbitities from both clinical and genetic perspectives. Specifically, she will investigate potential correlations between genetic haplotypes and clinical variables such as symptom clusters and particular environmental variables in TS and TS spectrum disorders. This proposal has specific aims: 1) to expand the clinical data collected for the genetic study of TS for additional clinical and epidemiological investigations. a) to carefully characterize the phenomenology of TS by collecting specific information on a variety of clinical variables, and to evaluate the extent of comorbid disorders such as obsessive compulsive disorder (OCD) in the study sample. b) to evaluate the presence and extent of selected environmental variables (such as birth trauma) hypothesized to influence the course of TS; 2) to evaluate the relationship of high risk haplotypes and the presence or absence of specific environmental factors to specific clinical variables, such as presence or absence of comorbid disorders or symptom severity; 3) to identify and collect a sample of individuals with TS-spectrum disorders (such as chronic motor tic disorder), and to characterize these disorders with regard to associated comorbidities, associated environmental factors, and presence or absence of high risk TS aplotypes; and 4) to collect a sample of subjects with TS and TS-spectrum disorders from additional populations in order to formally assess relationships between genetic, environmental, and clinical factors identified in this study. The specific aims will be achieved by analyzing and correlating clinical and genetic information gathered from two genetically isolated populations, the Central Valley of Costa Rica and individuals of Ashkenazi Jewish descent in the United States. Clinical information will be collected in a systematic way, and will be expanded to include information on symptom types and severity, presence and severity of number of specific comorbidities, and presence of specific environmental factors postulated to be associated with TS. An additional study sample will be collected to investigate the role of these variables on TS spectrum disorders. Clinical and genetic information will be analyzed and correlations explored using a variety of statistical measures. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR APPROACHES TO CHILDHOOD PSYCHIATRIC DISORDERS Principal Investigator & Institution: State, Matthew W.; Assistant Professor; Child Study Center; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2002; Project Start 01-MAY-2002; Project End 30-APR-2007 Summary: This application presents a career development award proposal spanning the fields of child psychiatry, molecular cytogenetics and molecular genetics. The near-term objective of this submission is to develop an independent program in patient-oriented research that focuses on identifying genes that contribute to serious psychiatric disorders. The ultimate aim of the applicant is to contribute to the translation of advances in genetics into improvements in diagnosis, treatment and prevention of childhood developmental and neuropsychiatric illnesses. After completing clinical training in adult and child psychiatry, the applicant participated in a three-year NIMH funded patient-oriented research fellowship at the Yale Child Study Center (YCSC). During this time, he simultaneously pursued an expertise in molecular genetics by enrolling in the Ph.D. program in the Department of Genetics at Yale. Dr. State was

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appointed Assistant Professor in the Child Study Center (Department of Child Psychiatry) in July of 2000. He currently divides his time between attending in the Tourette syndrome (TS) and Obsessive Compulsive Disorder (OCD) clinics and conducting research in the laboratory. This career award will provide vital support for his efforts to bridge clinical and basic science research. It will facilitate his continued patient-oriented research training, allow him to develop further expertise in relevant areas of molecular genetics and molecular cytogenetics, and provide the opportunity to achieve full scientific independence. The research plan presented below centers on the identification and characterization of genes that reside within a small region around a chromosomal inversion breakpoint found in a patient with a Tourette syndrome/Obsessive Compulsive Disorder (TS/OCD) phenotype. The developmental expression pattern of these genes will be assessed and the transcripts will be prioritized for further study with respect to their role in the TS/OCD spectrum of disorders. The proposal also plans for the development of a repository of cytogenetic abnormalities in well- characterized patients with TS/OCD phenotypes. The overarching objective of the award proposal, comprising both the career development and research plans, is to identify candidate genes in childhood neuropsychiatric disorders as a prelude to further investigations within the Child Study Center and the Children's Clinical Research Center (CCRC) that will focus on the relevance of these genes for the diagnosis, treatment, and natural history of TS/OCD. To help reach his long-term career objectives, the applicant has arranged for an outstanding group of mentors and advisors to provide guidance with respect to the design and conduct of his research, assistance in mastering the organizational challenges of running a successful research program, and training in the ethical issues attending research. He has formulated a plan for additional didactics and intensive workshops that will deepen his understanding of clinical statistical methodology, population genetics, gene expression analysis, genomics, and bioinformatics. Finally, his overall career development plan is made possible by the existence at Yale of a multidisciplinary team conducting translational research into the pathogenesis and treatment of childhood neuropsychiatnc disorders including TS/OCD, as well as the availability of the Children's Clinical Research Center (CCRC) which serves as a key resource in the conduct of this ongoing research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR GENETICS OF OBSESSIVE COMPULSIVE DISORDER Principal Investigator & Institution: Hanna, Gregory L.; Associate Professor; Psychiatry; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2001; Project Start 15-AUG-1999; Project End 31-JUL-2004 Summary: (Adapted from the Investigator's Abstract): Obsessive-compulsive disorder (OCD) is a common psychiatric disorder with a lifetime prevalence of 2.5 percent. Family studies indicate that OCD and sub-clinical obsessive-compulsive symptoms are familial. About one third of cases have onset by age 15 years. Recent family studies of OCS suggest that an early onset is associated with increased familial risk. The long-term goal of this project is to improve our understanding of the etiology of OCD by identifying susceptibility loci involved in early-onset OCD and determining the expression of these loci. An initial collection of families with early-onset OCD will be expanded through ascertainment of an additional 120 families with early-onset probands in which there is an affected sibling or second-degree relative. DNA from family members will be genotyped with mapped microsatellite markers and amplified by multiplex PCR spaced about every 10 cM. Parametric and nonparametric linkage

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Obsessive Compulsive Disorder

analyses will be performed. Once evidence for linkage between early-onset OCD and a genetic marker is found, more precise gene localization will be pursued. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOOD AND ANXIETY DISORDERS IN PREGNANCY AND LACTATION Principal Investigator & Institution: Stowe, Zachary N.; Associate Professor and Director; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2007 Summary: The treatment of mental illness during pregnancy has gained considerable attention over the past decade. The majority of this attention has focused on antidepressants and major depression, with far less consideration of anxiety disorders and bipolar disorder. The treatment guidelines for mental illness during pregnancy and lactation remain empiric and continue to emphasize the risk/benefit assessment. The lack of data on the course of illness, the impact of pregnancy and lactation of the metabolism and distribution of pharmacological treatments, and the extent of fetal and neonatal medication exposure underscores the empiric nature and prematurity of such guidelines. The current project will enhance and extend the data derived from an ongoing collaborative R01 MH56555-01A2 (Stowe) focused on the relapse of major depression in pregnant women taking antidepressant proximate to conception and K23 MH 63507-01 (Newport) investigating psychosis during pregnancy. We will prospectively follow women with major depression (MID), bipolar disorder (BPD), panic disorder (PD), and obsessive-compulsive disorder (OCD) through pregnancy and the first postpartum year. Many of these women may chose to continue medications such as antidepressants, mood stabilizers, and antipsychotic medications either during pregnancy and/or take medications postpartum. Monthly serum sampling and GCRC admissions will provide novel data.regarding the metabolism, distribution, and fetal/neonatal exposure to these compounds. These PK/PD models will be expanded to include assessment of pharmacogenetic factors of metabolic capacity and protein binding. Similarly, prospective documentation of additional exposures, sex steroid concentrations, and psychosocial variables will further refine such models and provide preliminary assessment of factors (other than medication concentrations) that may influence the course of illness and obstetrical outcome. The current project will utilize the core components to address the deficits in the current literature, affords a diagnostically diverse group of women that may be germane to the results obtained in Project 2 with respect to co-morbidity and the use of similar medications in a nonepileptic population. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: NEUROANATOMY AND PHARMACOTHERAPY OF OCD AND MAJOR DEPRES Principal Investigator & Institution: Saxena, Sanjaya; Psychiatry; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2001; Project Start 10-JUN-1999; Project End 31-MAY-2004 Summary: This application proposes Sanjaya Saxena, M.D. for a Mentored PatientOriented Research Career Development Award. The overall goals are to provide him with the conceptual background and research skills necessary for him to conduct patient-oriented research on obsessive-compulsive disorder (OCD) and major depressive disorder (MDD). Under the guidance of his Primary Mentor and Expert

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Consultants, he will be trained in neuroanatomy, neuropsychopharmacology, functional neuroimaging, quantitative image analysis, biostatistics, research design, and research ethics. Building upon his prior work in functional brain imaging in OCD and MDD, as well as in pharmacotherapy for refractory OCD, his research during the Award period will include two main studies, proposed herein, on the functional neuroanatomy, pharmacotherapy, and differential time course of response to treatment of OCD and MDD, studying a total of 42 subjects: 1) Cerebral Metabolic Changes with Treatment of Concurrent OCD and MDD: This study will use [18F]-fluoro-deoxyglucose positron emission tomography (FDG-PET), to delineate the specific brain system mediation of OCD symptoms and MDD symptoms occurring simultaneously, in patients treated with paroxetine, a medication shown to be effective for both disorders. Differential metabolic changes occurring along parallel, frontal-subcortical circuits within the same brain will be measured after four weeks and again, after twelve weeks of treatment, and will be correlated with changes in specific symptoms. Understanding the mediation of OCD and MDD by frontal-subcortical circuits, as well as the differential time course of pharmacological effects on these circuits, may lead to improved treatments for both of these common disorders in the future. 2) Cerebral Metabolic Predictors of Response to Paroxetine and Risperidone in Refractory OCD: This study has the following specific aims: a) to identify cerebral metabolic patterns with FDG-PET that might predict response to paroxetine alone vs. paroxetine plus risperidone, b) to identify symptoms or other clinical variables, such as level of insight or delusionality, which might predict response to adjunctive risperidone, and c) to examine the efficacy of adjunctive risperidone for OCD patients who are refractory to paroxetine. With the additional skills and experience acquired during the Award period, Dr. Saxena will be well-prepared to compete for independent research support, and to conduct patient-oriented, neuroimaging and pharmacological research on OCD and MDD, with the long-term goal of improving treatment for these disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NEUROBIOLOGY AND GENETICS OF PANIC, TS, AND OCD Principal Investigator & Institution: Gelernter, Joel E.; Professor; Psychiatry; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2001; Project Start 01-SEP-1996; Project End 28-FEB-2002 Summary: NEUROBIOLOGY AND GENETICS OF PANIC, TS, AND OCD. This is an application for an NIMH K02 (Independent Scientist) award. The goal of the proposal is to continue specialized training for the PI, a psychiatrist, in molecular and population genetics. The aims of the research are to (a) locate genes affecting risk for panic disorder by genetic linkage; (b) identify genes influencing risk for Tourette's syndrome and obsessive-compulsive disorder using the haplotype relative risk (HRR) family association method; (c) identify genes associated with specific phenotypes (recognized, eg, by imaging studies) within groups affected with illness using association methods; and (d) identify specific mutations associated with phenotype by mutational analysis and sequencing. Under some circumstances, genome scan- directed linkage studies are most useful in identifying genes predisposing to illness; under other circumstances, HRR studies may be more efficient. For very strong candidate gene hypotheses, mutational analysis may be employed directly. Preliminary results have been generated using all of these methods. For our panic disorder linkage project ("a"), we have obtained DNA from 201 individuals in 21 families, as of May 1995. We have used the HRR method to identify a genetic association between Tourette's syndrome and an allele at the D4 dopamine receptor locus ('b"). In the area of genotype/phenotype association,

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Obsessive Compulsive Disorder

we have reported an association between cocaine-induced paranoia and dopamine transporter alleles; we have obtained preliminary data using SPECT imaging techniques regarding the relationship between alleles at the D2 dopamine receptor locus (DRD2) and brain D2 receptor density ("c". We propose to complete a genome scan for the panic disorder linkage project; attempt to identify other genes influencing risk for Tourette's syndrome and obsessive-compulsive disorder; and identify other genotype-phenotype relationships using imaging studies as a way to ascertain phenotype directly. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NEUROIMAGING MONITORING

OF

ATTENTIONAL

CONTROL

AND

Principal Investigator & Institution: Luks, Tracy L.; Radiology; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 94122 Timing: Fiscal Year 2002; Project Start 13-DEC-2002 Summary: Two frontal brain regions, Anterior Cingulate Cortex (ACC) and Dorsolateral Prefrontal Cortex (DLPFC) appear to be particularly involved in attentional control and self-monitoring. There is evidence that while these regions work in tandem to regulate behavioral, DLPFC is specifically responsible for allocating attention to meet task demands, and ACC is specifically responsible for monitoring the stimulus processing and responding for performance difficulties and signaling the DLPFC and general arousal systems when reallocation of attention is needed. Important recent studies have revealed the complexities of the roles of these areas, and the need to understand their interactions. The four proposed experiments will use fMRI, EEG and behavior measures to address the following unresolved issues: 1) Whether ACC is involved in switching attention states, and whether separate subregions of the ACC are involved in the allocation of attention and in the detection of processing conflict, 2) How preparatory attention and performance monitoring functions interact, 3) What regions are responsible for reallocating attention to resole processing conflict, and 4) Whether the ACC or DLPFC are in error evaluation, and if so, whether these operations involve different subregions than preparatory attention and monitoring operations. This research will add to our understanding of the mechanisms that underlie dynamic behavioral control, and will inform the study of neurological disorders in which behavioral control is impaired, such as Schizophrenia, Alzheimer's Disease, Attention Deficit Disorder, and Obsessive Compulsive Disorder. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NEUROIMAGING STUDIES OF FRONTAL LOBE PATHOLOGY IN OCD Principal Investigator & Institution: Szeszko, Philip R.; Long Island Jewish Medical Center 270-05 76Th Ave New Hyde Park, Ny 11040 Timing: Fiscal Year 2001; Project Start 01-MAY-2001; Project End 30-APR-2006 Summary: (Provided by applicant): This revised application for a Mentored Research Scientist Development Award (KOl) is from a licensed clinical psychologist and Assistant Professor of Psychiatry. He is proposing a research career development plan that will enable him to learn how to use diffusion tensor imaging and functional magnetic resonance imaging techniques to better elucidate the neurobiology and neuropsychology of obsessive-compulsive disorder (OCD). Compared to other major psychiatric disorders such as schizophrenia and depression there have been fewer neuroimaging studies in OCD, and the majority of studies conducted thus far have

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utilized either PET or SPECT. Moreover, the neural mechanisms underlying cognitive dysfunction in OCD have been poorly elaborated. The applicant has preliminary data (Szeszko et al 1999) implicating orbital frontal lobe structural abnormalities in OCD using morphometric methods and wants to learn how to conduct additional studies investigating the frontal lobes of these patients. The training plan would increase the applicant's knowledge in three broad domains: (1) neurobiology, phenomenology and pharmacology of OCD; (2) diffusion tensor imaging and (3) neuropsychology of OCD and cognitive neuroscience applications of fMRI in OCD. The training goals will be accomplished through the completion of the research plan, which will examine the relative contributions of dorsal and ventral frontal regions to the pathophysiology of OCD using brain morphometry, diffusion tensor imaging, functional magnetic resonance imaging and comprehensive neuropsychological assessment. In collaboration with the applicant's mentors and consultants various statistical and image processing techniques will be used to analyze and interpret the neuroimaging data and the functional correlates of structural brain pathology will be identified. Completion of the training goals and research studies are expected to provide the applicant with the knowledge and experience to develop into an independent investigator capable of conducting high quality neuroimaging studies in OCD and to apply for an ROl. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DISORDERS

NEUROIMMUNOLOGY

OF

CHILDHOOD

PSYCHIATRIC

Principal Investigator & Institution: Murphy, Tanya K.; Associate Professor; Psychiatry; University of Florida Gainesville, Fl 32611 Timing: Fiscal Year 2001; Project Start 15-FEB-2001; Project End 31-JAN-2006 Summary: This is a request for a Mentored Patient-Oriented Research Career Development Award. The purpose of this award is to support the supervised research experience coupled with critical didactic training to develop the skills necessary to become an independent investigator in the area of child neuroimmunology research. An example of a neuropsychiatric illness believed to have an autoimmune etiology is Sydenham's chorea (SC). An interplay of genetic, developmental, and environmental factors determines vulnerability to this complication of a streptococcal infection. It has been hypothesized that SC may be a medical model for some forms of tic and obsessive compulsive disorders (OCD). Evidence to support an autoimmune etiology in these and other child neuropsychiatric disorders has been increasing. It is an exciting area to explore as future developments may lead to additional diagnostic and treatment approaches to these disorders. The aim of the award is to promote career development in neuroimmunology of child neuropsychiatric disorders via didactic training in these areas and conducting a research plan under the mentorship of experts in OCD and Tourette's syndrome (TS) patient-oriented research, ileuroimmunology and related laboratory techniques, and pediatric infectious disease/immunology. This multidisciplinary training is necessary to foster skills in patient-oriented research in child neuropsychiatry and the translation from basic science skills needed to study mechanisms of disease. The proposed research study will test the following hypotheses: 1) Is there, evidence of immune dysfunction in children with OCD and/or chronic tic disorders (CTD)?;and 2) Is immune dysfunction more evident during symptom exacerbations? Exploring the role of immune responses in pediatric neuropsychiatry would provide the opportunity to fully develop skills in research design and methodology, patient characterization and neuroimmunology laboratory techniques. This award, along with support from the University Florida Brain Institute and the

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Obsessive Compulsive Disorder

Department of Psychiatry, will enable the candidate to build a strong foundation of research skills needed to become an independent investigator. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NEURONAL DYSFUNCTION IN PREMENSTRUAL DYSPHORIC DISORDER Principal Investigator & Institution: Epperson, Cynthia N.; Assistant Professor; Psychiatry; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2001; Project Start 05-DEC-1999; Project End 30-NOV-2004 Summary: After a year and a half on the faculty in the Departments of Psychiatry and Obstetrics and Gynecology, I find myself at a crossroads in my career development. I have been involved primarily in clinical postpartum mood disorders and obsessive compulsive disorders research. However, my clinical and scientific interests have shifted. During my tenure as the Director of the Yale Behavioral Gynecology Program, I have developed an appreciation for the complex interplay between neuroactive steroids and the neurochemistry involved in regulation of mood and cognition. In addition, I have developed basic skills in proton-magnetic resonance spectroscopy (1H-MRS), a novel, non-invasive method to quantify in vivo amino acid neurotransmitters. I have designed the K23 award to enable me to pursue a five-year comprehensive researchtraining plan. This plan will provide me with the skills necessary to become an independent investigator who can apply MRS techniques to determine the impact of neurosteroids on GABA and glutamate neurotransmission as they reltate to the pathophysiology and treatment of premenstrual dysphoric disorder (PMDD). Without support from a K23 award, I would be required to continue my significant administrative and clinical duties as the director of a busy clinical program and would not be afforded the opportunity to make this shift in my scientific career. We have obtained exciting pilot data using 1H-MRS demonstrating fluctuations in cortical GABA levels across the menstrual cycle of women with PMDD and health menstruating controls with between group differences in the fluctuation pattern. I propose to continue these investigations with three goals. 1) To conduct the first longitudinal (across the menstrual cycle) characterization of both frontal and occipital cortex GABAergic and glutamatergic systems in healthy menstruating women and those with PMDD. 2) To determine the relationship between neuroactive steroids and amino acid neurotransmitter levels across the menstrual cycle. Amd 3) To determine whether the selective serotonin reuptake inhibitor fluoxetine exert its therapeutic effect in the treatment of PMDD via modulation of neuroactive steroids and/or GABAergic and/or glutamateric function. I have identified several key areas where I will require additional training in order to advance the use of 1H-MRS techniques to the study of PMDD. These areas include; 1) nuclear magnetic resonance application of reproductive endocrinology to PMDD research, 3) neurochemistry and kinetic modeling, and 4) neuropharmacology and clinical trials methodologies. Under the mentorship of my Yale mentors Drs. Krystal, Rothman, and Naftolin and my extra-mural mentors Drs. Rubinow and Schmidt, the career development program outlined in this program is certain to prepare me for a career as an neuroendocrinologist who can utilize MRS technology to study the impact of neuroactive steroids on brain neurochemistry. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: OBSESSIONS & COMPULSIONS: PRADER-WILLI & OTHER SYNDROMES Principal Investigator & Institution: Dykens, Elisabeth M.; Associate Professor; None; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2001; Project Start 01-AUG-1997; Project End 31-MAR-2003 Summary: (adapted from the applicant's abstract): Prader-Willi syndrome (PWS) has long been characterized by hyperphagia, food obsessions, and increased risks of obesity in affected individuals. Although less well-described, many people with PWS show obsessions and compulsions not related to food, as well as significant behavioral dysfunction. The proposed study will examine these obsessions, compulsions, and other maladaptive features, filling a long-standing behavioral research void in this complex developmental disorder. To this aim, the investigators propose to identify the onset, course, and phenomenology of obsessive-compulsive symptoms in PWS, and how these relate to children with obsessive-compulsive disorder (OCD). PWS is hypothesized to represent a specific clinical subtype of OCD, opening up possible roles for genomic imprinting or the PWS Critical Region in delineating these subtypes. It is hypothesized that compulsivity in PWS has an unusually early-onset, and that salient features of the PWS cognitive-behavioral phenotype may provide new clues into how compulsivity is expressed in young children. Early-onset compulsivity is also likely associated with aspects of hyperphagia and of normative development. The second aim is to identify possible mechanisms in PWS that mediate the expression of compulsivity. The proposed study hypothesizes that whole-blood serotonin will mediate symptom expression, and that subtle differences in symptoms may be seen across PWS subjects with paternallyderived deletions at 15q11-q13 versus those with maternal uniparental disomy of chromosome 15. Third, the investigators aim to determine the distinctiveness of compulsivity in PWS relative to children with Williams syndrome (WS), and Down syndrome (DS). WS is a particularly powerful contrast group as it is characterized by increased anxiety and obsessional thinking. The three aims will be addressed in two ways: 1) a longitudinal study of 60 children with PWS, WS, and DS aged 2 to 7 years who are tested twice, two years apart; and 2) a cross-sectional study of 35 children with PWS aged 10-14 years who are compared to subjects with WS, DS, and appropriately matched children with OCD. Findings will shed new light on treatment, on certain subtypes of OCD, and on the range and correlates of PWS' complex behavioral phenotype. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: OBSESSIONS/COMPULSIONS IN HUNTINGTON'S DISEASE Principal Investigator & Institution: Anderson, Karen E.; Gertrude H Sergievsky Center; Columbia University Health Sciences New York, Ny 10032 Timing: Fiscal Year 2001; Project Start 01-APR-2001; Project End 30-SEP-2001 Summary: (provided by applicant) Huntington's disease (HD) is a neurological illness with prominent psychiatric comorbidity. Obsessions and compulsion appear to be highly represented in HD, but have not been studied. There is compelling evidence that obsessive-compulsive disorder (OCD) is related to dysfunctional cortico-striatal networks. Because it is a neurological disorder with well-characterized striatal pathology, and accurate genetic testing, HD provides a unique opportunity for study of these symptoms In this Mentored Clinical Scientist Development Award proposal, a program is outlined that will prepare the candidate to become an independent

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Obsessive Compulsive Disorder

investigator. The candidate will learn how to evaluate obsessive and compulsive symptoms in HI) patients. HD patients' data will be compared with data from primary OCD patients to examine how obsessions and ompulsions may differ in a neurological illness that primarily affects the striatum. Clinical and neuropsychological correlate of OCD in HD will be explored. Cognitive activation paradigms will be used with neuroimaging studies to engage network implicated in primary OCD. First, task-related cerebral activation changes particular to HD itself will be studied, and these networks will be related to presence or absence of obsessive and compulsive symptoms. Supervision of the candidate during this award will be provided by these mentors: Drs. Yaakov Stern (training coordination, neuropsychology supervision), Karen Marder (neurological expertise, evaluation of HD), Michael Liebowit training in evaluation of obsessive and compulsive symptoms), and Dr. James Haxby (neuro-imaging). Advanced instruction n the neuroanatomy of frontal-striatal circuitry, including handon correlation of brain slices with Magnetic Resonanc mages, is included. The goals of this award are to promote the candidate's training, study psychiatric symptoms in HD, and Ldd to current understanding of neural circuitry implicated in HD. The ultimate goal is to provide the candidate with the skill and knowledge base to become an independent, multidisciplinary investigator of neuropsychiatric illness. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: OCD TREATMENT OUTCOMES--BEYOND PHASE 3 DRUG TRIALS Principal Investigator & Institution: Ackerman, Deborah L.; Epidemiology; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2001; Project Start 01-AUG-1998; Project End 31-JUL-2003 Summary: The research career award would provide Dr. Ackerman with didactic and research training to conduct epidemiologic studies of treatment outcomes and clinical trials, including methods of psychiatric screening and psychological assessment, diagnostic procedures, and advanced statistical techniques. Her previous research has focused on the identification of predictors of response to psychotherapeutics by performing secondary analyses of data collected by pharmaceutical companies in randomized clinical trials (RCTs). During the first 3 years of this grant, formal course work and directed study will train Dr. Ackerman in the biological and methodological principles of clinical psychopharmacology and pharmacoepidemiology. An observational study during the fourth and fifth years will evaluate treatment response in obsessive-compulsive disorder (OCD) and extend the findings from industry-sponsored clinical trials to clinic settings. A cohort will be drawn by retrospective chart review of all patients with OCD treated in the UCLA Neuropsychiatric Hospital Mood and Anxiety Disorders Program during the previous 4 years. Two types of cohorts will be chosen. One will include all patients and will assess short and long-term outcomes of all treatments. The other will be restricted to patients who received either clomipramine or fluoxetine and will be subject to the same exclusion criteria and follow-up periods that were employed in the Phase 3 RCTs sponsored by the two drugs' developers. Results from the two cohorts will be compared with respect to predictors of all possible outcomes, including response, partial response, added medications, drop- outs. Predictors of response from the cohorts will then be compared with predictors of response that were identified by analyzing data from two Phase 3 trials of clomipramine and fluoxetine. Statistical methods will be used that can identify and resolve problems of biological heterogeneity, i.e., when people vary in their response to a particular treatment and in their risk for a given condition, and multiple- comparison artifacts that are frequently encountered in analyzing data from multicenter studies.

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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ONDANSETRON TREATMENT FOR OBSESSIVE COMPULSIVE DISORDER Principal Investigator & Institution: Hewlett, William A.; Assistant Professor of Psychiatry; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2001 Summary: Determine the efficacy of low-dose ondansetron in the treatment of obsessive-compulsive disorder. After the nine week trial of treatment w/ondansetron, assessment of the OCD patients completing this trial as specified will show a significant change* in the Yale Brown Obsessive Compulsive Scale (YBOCS) score. Scores of a patient self rating scale (PSRS), and the YBOCS Clinical Global Impression (CGI) rating will show significant changes as secondary measures. Over the nine week period of treatment w/ondansetron, at least 1/3 of OCD patients entering the study will show a clinically significant improvement (25% reduction) of their OCD symptoms which will manifest in their total YBOCS scores. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ORAL ZIPRASIDONE IN TOURETTE'S SYNDROME, OBSESSIVE COMPULSIVE DISORDER Principal Investigator & Institution: Scahill, Lawrence S.; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2001 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PANDAS AND STREP INFECTION: ARE THEY LINKED? Principal Investigator & Institution: Kurlan, Roger M.; Professor; Neurology; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2001; Project Start 25-SEP-2001; Project End 31-JUL-2005 Summary: Sydenham's chorea is the only accepted immune-mediated central nervous system manifestation of group A beta hemolytic streptococcal (GABHS) infection. Several lines of evidence now suggest that there may be a spectrum of post-GABHS immune- mediated neurobehavioral sequelae termed "Pediatric Autoimmune Neuropsychiatric Disorders after Streptococcal Infection (PANDAS)". Tics, including Tourette's syndrome (TS), and obsessive-compulsive disorder (OCD) have been reported as the characteristic features of PANDAS. Proposed is a multicenter prospective case control cohort study involving 40 cases of PANDAS and 40 matched controls with TS and/or OCD but without evidence of PANDAS. All subjects will undergo intensive clinical and laboratory prospective observation for 24 months to determine whether antecedent GABHS infection is: 1) temporally associated with exacerbations of PANDAS, 2) specifically associated with exacerbations of tics and OCD, and 3) a specific trigger for exacerbations of PANDAS. All determinations of case/control status, GABHS infection and clinical exacerbation will be determined independently by blinded review in order to limit selection and clinical biases. Establishing a post-infectious etiology for PANDAS would dramatically change our understanding of the causes of TS and OCD, alter our therapeutic approach and may have a critical public health implication of preventing potentially fatal rheumatic cardiac

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Obsessive Compulsive Disorder

sequelae in affected children. Disproving the PANDAS hypothesis would prevent the use of expensive and potentially dangerous therapies (e.g., plasma exchange, immune globulin, antibiotics) that have been proposed for PANDAS patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PEDIATRIC OBSESSIVE COMPULSIVE DISORDER Principal Investigator & Institution: Rosenberg, David R.; Professor; Psychiatry & Behav Neuroscis; Wayne State University 656 W. Kirby Detroit, Mi 48202 Timing: Fiscal Year 2001; Project Start 01-MAY-2001; Project End 30-APR-2006 Summary: Obsessive compulsive disorder (OCD) is a severe, prevalent and chronically disabling disorder that often emerges during childhood. Nonetheless, pediatric OCD remains an understudied disorder. One reason is that there are too few researchers with sufficient skills and understanding in both developmental neurobiology and neuropsychopharmacology. Treatment studies using biological markers as moderator (present at baseline) and mediator (changing with treatment) may potentially lead to a mechanistic understanding of the pathogenesis and maintenance of the illness, which may in turn result in the development of new diagnostic and treatment approaches. This is critical because at least one third of patients do not respond at all, even after apparently adequate treatment trials. Treatment-refractory patients are also more likely to have early onset of illness. Preliminary studies suggest a reversible glutamatergically mediated thalamocortical-striatal dysfunction in OCD that may serve as a pathophysiological and treatment response marker. In this context, the candidate's chief aim is to use time liberated by the K24 Award to develop, evaluate and disseminate biological outcome markers of OCD and determine their relevance for improved diagnostic assessment and treatment. To this end, the K24 career development plan (1 )furthers the candidate's knowledge in clinical neuroscience emphasizing the integration and translation of brain imaging measurement as it relates to neurodiagnostic assessment and treatment, 2) furthers the candidates knowledge in the conduct and design of relevant clinical trials for treatment development, and (3) emphasizes knowledge dissemination of the translational components of this research, including a proposed T32 training grant focused on psychopathology and treatment of pediatric mental disorders. The K24 research plan centers on ongoing and proposed treatment outcome studies using brain imaging to help elucidate neurobiological markers in childhood OCD. The K24 will advance sustained practical and theoretical contributions to the candidates chosen research area. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PHARMACOTHERAPY OF ADOLESCENT BODY DYSMORPHIC DISORDER Principal Investigator & Institution: Hollander, Eric; Associate Professor; Psychiatry; Mount Sinai School of Medicine of Nyu of New York University New York, Ny 10029 Timing: Fiscal Year 2001; Project Start 15-MAR-1999; Project End 28-FEB-2003 Summary: This study proposes to investigate the treatment response of body dysmorphic disorder (BDD) in adolescents. Body dysmorphic disorder, a preoccupation with an imagined or slight defect in appearance, is a distressing and impairing disorder that is more common than is generally recognized. BDD usually begin during childhood or adolescence, but its treatment in adolescents has not been investigated. Such investigation is important because BDD appears to often be chronic and to cause considerable morbidity. It is associated with high rates of social and

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academic/occupational impairment, being housebound, psychiatric hospitalization, suicidal ideation, and suicide attempts. Preliminary data from adults and adolescents suggest that BDD and its delusional variant (a type of delusional disorder, somatic type) may respond to serotonin-re-uptake inhibitors. Furthermore, similarities between BDD and obsessive compulsive disorder (OCD) make these medications promising for adolescent BDD. The primary specific aim of this study is to assess the efficacy and safety of fluoxetine versus placebo in BDD and its delusional disorder variant in 100 adolescents age 12-17. The proposed study will be a 12-week double-blind parallelgroup trial that will occur at three sites: Butler Hospital/Brown University, Mount Sinai School of Medicine, and The University of Cincinnati School of Medicine. A secondary specific aim is to explore the predictors of treatment response. The hypothesis to be tested is that delusionality (insight), comorbid major depression or OCD, and illness severity will not predict fluoxetine response. The proposed study will provide needed data on BDD's treatment in adolescents. It will be the first controlled treatment trial of BDD in an adolescent age group. Such investigation is needed because this underrecognized, often-secret disorder usually begins during adolescence and can cause significant distress and impairment in functioning. When untreated, adolescent-onset BDD appears to often interfere with the developmental tasks of adolescence, to persist, and to cause substantial morbidity through out the life span. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: POLYMORPHISMS OF DOPAMINERGIC GENES Principal Investigator & Institution: Kidd, Kenneth K.; Professor of Genetics and Psychiatry; Genetics; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2001; Project Start 01-JUN-2000; Project End 31-MAY-2003 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PROSPECTIVE STUDY OF 'PANDAS' Principal Investigator & Institution: Goodman, Wayne K.; Professor and Chairman; Psychiatry; University of Florida Gainesville, Fl 32611 Timing: Fiscal Year 2002; Project Start 26-APR-2002; Project End 31-MAR-2007 Summary: The existence of PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus) continues to be questioned. Confirmation of a relationship of this putative subtype of obsessive compulsive disorder (OCD) and Tourette's Syndrome (TS) to an antecedent Group A Streptococcal (GAS) has gained considerable practical importance because of implications for treatment and prevention interventions that are radically different from the standard practice of administering psychotropics (such as SRIs or neuroleptics) for symptomatic relief. In particular, a study showing the efficacy of plasmapheresis and intravenous immunoglobulin treatment in PANDAS has stimulated public and professional debate, with some parents demanding these interventions for their children and most clinician-scientists urging caution. The need for further research is clear, but no one study will address all the questions surrounding PANDAS. A series of studies designed to test specific aspects of the pathogen-triggered autoimmune hypothesis will be required. The primary specific aim of the present study is to evaluate whether episodes or exacerbations in obsessive-compulsive (OC) or tic symptoms in children with OCD or TS are significantly associated with antecedent GAS infection, as reflected in elevated serum

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antibody titers. Seventy-nine children (ages 4 to 12 years) with OCD, TS, or Chronic Multiple Tic Disorder (CMT) will participate in this study and be followed for approximately two and a half years, a 28-month period, at monthly intervals for clinical ratings of neuropsychiatric symptoms and serological testing for GAS infection (ASO and AntiDNAse B). The study will be conducted at two institutions, the University of Florida and the National Institute of Mental Health, using identical designs and procedures. In order to identify a cohort that exhibits the desired pattern of exacerbation/regression of symptoms and to allow for attrition, we estimate that approximately 180 patients will have to be enrolled over the five-year study. Blood samples will be obtained at each visit for GAS antibodies and for exploratory immunologic studies. Should clinical signs of pharyngitis develop, throat cultures will be ordered and, if positive for GAS, appropriate antibiotic treatment will be instituted. These cases, estimated at n = 45, may provide useful information on the effect of antibiotics to attenuate exacerbations or influence OC/tic symptom course. In this cohort with clinical GAS pharyngitis, the rate of exacerbations for the 6-months following treatment will be compared to the corresponding period prior to treatment. The proposed longitudinal study will furnish needed data on the validity of the PANDAS concept and help generate reliable operational criteria for identifying cases at risk of GAS-triggered OC or tic symptoms. The results will help determine if antimicrobial interventions are warranted in certain subtypes of pediatric OCD or TS. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PULSE LOADED IV CLOMIPRAMINE IN OBSESSIVE COMPULSIVE DIS Principal Investigator & Institution: Koran, Lorrin M.; Professor; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2001 Summary: Study patients will receive, double-blind, either intravenous or oral clomipramine on two consecutive days: 150 mg on Day 1 and 200 mg on Day 2, administered in the Stanford General Clinical Research Center (inpatient unit), with continuous monitoring of vital signs. On the fourth day after completing the pulse loading, the patient will come to the Psychiatry outpatient clinic to begin 12 weeks of oral clomipramine, starting at 200 mg/day and increasing rapidly, as tolerated, to 250 mg/day. To be eligible, patients must be aged 18-55, in good physical health, able to discontinue all medications except a benzodiazepine if necessary, have OCD of moderate or greater severity for at least one year, no psychotic disorder, no substance or alcohol abuse/dependence diagnosis within the previous six months, no history of bipolar disorder, no tic disorder or Tourette's syndrome, and no personality disorder severe enough to interfere with cooperation with the study procedures. They must also have failed to benefit markedly from at least two adequate (>= 8 weeks) trial of serotonin reuptake inhibitors: citalopram 20 mg/day: clomipramine 200 mg/day; fluoxetine 40 mg/day; fluvoxamine 200 mg/day; paroxetine 40 mg/day; setraline 100 mg/day. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: R21 PROJECT: ST. JOHN'S WORT VS. PLACEBO IN OCD Principal Investigator & Institution: Kobak, Kenneth A.; Senior Research Scientist; Dean Fdn for Health, Research & Educatn Research and Education Middleton, Wi 53562 Timing: Fiscal Year 2002; Project Start 15-APR-2002; Project End 31-JAN-2004

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Summary: Obsessive compulsive disorder (OCD), a syndrome characterized by obsessions and compulsions, has a lifetime prevalence of 1-2%. Accumulating evidence in support of the serotonergic hypothesis on the etiology of OCD led to several serotonin reuptake inhibitors (SSRIs) being approved as a treatment for this disorder. However, even with adequate dose and duration non-response or partial response is the role. In addition, side effects with the SSRIs prompt the search for better tolerated compounds (e.g., drop-out rates in the multi-center trials of fluoxetine, fluvoxamine, sertraline, and paroxetine were 23%, 24%, 27%, and 20% respectively. There has been considerable worldwide interest in St. John's Wort (SJW) (Hypericum perforatum) as a treatment from mild to moderate depression. To date, there have been 23 randomized trials suggests SJW is more effective than placebo for the treatment of outpatients with mild to moderate depression. SJW is very well tolerated with mild side effects observed in only 2.5% of cases in a large drug monitoring study. SJW's mechanism of action is postulated by be via inhibition of the synaptosomal uptake of serotonin, and thus there is a suggestion that SJW may be effective for OCD. A recent 12- week open-label trial with 123 subjects with a fixed dose of 450 mg of hypericin twice daily found a significant change from baseline to endpoint, with a mean Y-BOCS change of 7.4 points (p=.002). Five of the 12 subjects previously failed to respond to a trial with an SSRI. The current study will be a 12-week, double-blind, placebo controlled parallel group study. The purpose of the study is to examine the efficacy and safety of SJW compared to placebo. Fifty subjects will be randomly assigned to SJW (Alterra bran, 450 mg, 1.35 hypericin) or matching placebo. This will be a fixed-dose design at 450 mg bid. An intent-to- treat analysis will be employed Subjects will be evaluated weekly for two weeks than biweekly thereafter. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RESEARCH IN PEDIATRIC ANXIETY DISORDERS Principal Investigator & Institution: March, John S.; Associate Professor; Psychiatry; Duke University Durham, Nc 27706 Timing: Fiscal Year 2001; Project Start 15-DEC-1998; Project End 30-NOV-2003 Summary: Anxiety disorders are among the most common and troublesome mental illnesses affecting children and adolescents. While the field has made considerable progress in developing empirically supported treatments for these conditions, the anxiety disorders still lag far behind the disruptive behavior disorders with respect to treatment research. One reason is that there are too few researchers with sufficient exposure to both cognitive-behavioral and pharmacological treatment interventions for anxious children, as well as the tenets and methods used in complex clinical trials and studies of mechanisms of improvement. As one of the few researchers, my chief aim is to use time liberated by this Independent Scientist Award (ISA) to develop, evaluate and disseminate new diagnostic and treatment approaches for the pediatric anxiety disorders. To this end, the ISA career development plan (1) further my knowledge of complex statistical procedures, evidence-based medicine and understanding of ethics in research, and (2), emphasizes knowledge dissemination, including a proposed T32 training grant focused on the treatment of pediatric mental disorders. The ISA research plan centers on ongoing and proposed NIMH- funded treatment outcome studies in Obsessive-Compulsive Disorder (OCD) and Post-traumatic Stress Disorder (PTSD). As with the preparatory Scientist Development Award for Clinicians (SDAC), the ISA will advance sustained practical and theoretical contributions to my chosen research area. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: RESEARCH TRAINING - BIOLOGICAL SCIENCES Principal Investigator & Institution: Duman, Ronald S.; Professor; Psychiatry; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2001; Project Start 01-JUL-1975; Project End 30-JUN-2003 Summary: The main purpose of the Biological Sciences Program in the Department of Psychiatry at Yale is to train postdoctoral fellows in biological and behavioral Sciences relevant to mental illness and health. To attain this goal, the program recruits two groups of postdoctoral trainees: 1) psychiatrists, generally after completing two or three years of clinical residency; 2) individuals with a Ph.D. degree in a basic science. To help fill a nationally recognized need, the aim of the program is to both increase the number of research psychiatrists with a grounding in basic biological sciences and to develop the interests of basic scientists in clinical problems as well as in interdisciplinary aspects of their own basic research. Thus, the overall aim is to promote cross-fertilization, between basic researchers and individuals who are experienced clinically. Extensive research collaboration between faculty of the training program further contributes to interdisciplinary experience of the trainee. It is expected that trainees coming out of this program will be able to bridge the gap between basic and clinical neuroscience in psychiatry. There are 21 faculty members in the program consisting of both basic and clinical researchers. The number of postdoctoral training slots requested is six, the same number as the current grant. The program typically involves training for approximately 2 years in one primary discipline but usually includes direct or collaborative interaction with other disciplines. Laboratory training is offered in the following areas: neuroanatomy, histochemistry, neurochemistry, molecular biology, electrophysiology, and behavior. Clinical research training is offered in behavioral assessment, biological measurements, and imaging techniques. In addition to specific research training, there are courses in Clinical Neuroscience and Neuropharmacology as well as seminars and regular Workshops in which Fellows present ongoing research to the entire group of faculty and trainees. The training proposal is related to the research objectives of NIMH by fostering the training of researchers to produce new knowledge about mental disorders and maladaptive behavior. Thus, basic and clinical research is carried out in areas related to anxiety (e.g., panic and post- traumatic stress disorder), obsessive compulsive disorder, schizophrenia, and affective illness. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SEROTONERGIC FUNCTION IN DEMENTIA Principal Investigator & Institution: Chow, Tiffany W.; Rotman Research Institute 3560 Bathurst St Toronto, Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2006 Summary: (provided by applicant): This study will initiate the candidate's career goal of finding evidence to guide management of neuropsychiatric disturbances in dementia by allowing her training in PET imaging with a serotonin receptor-specific radioligand and statistical analysis. The synergistic expertise of the mentors and facilities available to her at the University of Toronto cannot be reproduced in the US for this study. HYPOTHESIS: Anxiety, obsessive-compulsive behaviors and dysphoria in frontotemporal lobar degeneration (FTLD) are associated with a diminution in 5HT1A receptor density in frontal and temporal cortex. PET imaging can demonstrate and quantify these differences. SPECIFIC AIMS: 1) Quantify the difference in binding potential at 5HT1A receptors as derived from PET imaging with [11C]WAY-100635 in frontal and temporal cortical regions of interest between FTLD subjects and normal, age-

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and education-matched controls. 2) Compare the same PET findings between FTLD subjects with and without the mood symptoms. If changes in serotonergic function in frontal regions of interest correlate with the symptoms, this study will provide the basis for further investigations to identify serotonergic pharmacotherapy for such patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SEROTONIN-A TRAIT DISTURBANCE IN ANOREXIA NERVOSA? Principal Investigator & Institution: Kaye, Walter H.; Professor; Psychiatry; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2001; Project Start 01-AUG-1990; Project End 31-MAR-2003 Summary: Indirect evidence suggests that brain serotonin (5-HT) alterations occur in women with anorexia nervosa (AN) when they are underweight and after recovery. This competitive renewal will use new technologies that offer the potential of direct characterization of dynamic relationships between 5-HT receptor function and human behavior. We will assess 5-HT1A and 5-HT2A receptors. A defect in either may contribute to trait-related increased 5-HT neurotransmission associated with core AN symptoms, such as restricted feeding, obsessions with order and perfectionism, harm avoidance and negative affect. Our last funding period supports the possibility that starvation-induced changes may reduce 5-HT neuronal activity, which in turn reduces dysphoric affective states. Such receptor changes may also shed light on failure to respond to SSRIs. Over 4 years 3 groups of women (18 to 45 years old) will be studied: 1) 30 AN women who are underweight; 2) 30 women who are recovered (greater than 1 year normal menses, no bingeing and purging, and healthy and stable weight) from AN; 3) 30 healthy control women (CW). Each AN cohort will consist of 15 restrictingsubtypes and 15 binge- eating/purging subtypes. In Aim 1 Positron Emission Tomography (PET) imaging and [18F]altanserin will assess 5-HT2A postreceptor binding. Preliminary data support the possibility that recovered AN women will have a reduction of orbitofrontal 5-HT2A receptor binding associated with evidence of increased extracellular 5-HT. In comparison, underweight AN should have opposite findings. In Aim 2 PET imaging and [11C]WAY100635 will assess 5-HT1A receptor binding. Knockout gene studies in mice support the hypothesis that a malfunction of pre-synaptic raphe autoreceptors could contribute to increased 5-HT activity and behavioral symptoms in AN. Thus 1A binding may not change with state of the illness. Our last funding period found that a polymorphism (-1438G/A) in the promoter region of the 5-HT2A receptor gene was associated with AN. Aim 3 is a pilot study that will explore whether this or other 5-HT related polymorphisms, are associated with altered binding on PET or with behavioral symptoms. Aim 4 will test whether core AN symptoms or impulse control are related to 5-HT neuronal activity. The understanding of whether a biologic vulnerability, such as a 5-HT disturbance, occurs in AN may contribute to developing new treatment interventions for this often chronic and deadly disorder. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: STREP THROAT, SYDENHAM CHOREA, AND TOURETTE SYNDROME Principal Investigator & Institution: Mcmahon, William M.; Associate Professor; Psychiatry; University of Utah 200 S University St Salt Lake City, Ut 84112 Timing: Fiscal Year 2001; Project Start 01-MAR-2000; Project End 28-FEB-2005 Summary: This abstract is not available.

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Obsessive Compulsive Disorder

Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: STRUCTURAL AND FUNCTIONAL ANALYSES OF NEURONAL PTPS Principal Investigator & Institution: Lombroso, Paul J.; Associate Professor; Child Study Center; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2002; Project Start 01-JUN-1998; Project End 30-NOV-2003 Summary: (Adapted from applicant's abstract): My application for a K02 award reflects a natural progression of my scientific development, first as a child psychiatrist and then as a molecular biologist. From the beginning of my career as a research fellow in psychiatry and in molecular biology, and more recently as a faculty member in the Yale Child Study Center, the focus of my research has been on understanding underlying mechanisms in signaling pathways within the basal ganglia. Disruption of the normal signal transduction pathways within this region occurs in a number of neuropsychiatric disorders, including Tourette's syndrome and obsessive compulsive disorder, as well as being the site of action of the unwanted side effects of the major neuroleptics. The central goal of the proposed investigation is to study the structure and function of a family of protein tyrosine phosphatases, termed STEP. The family consists of both cytosolic and membrane-associated isoforms, as well as truncated variants that lack an active catalytic site. A striking feature is that some STEP isoforms contain transmembrane domains, PEST sequences, and polyproline-rich sequences. We hypothesize that these domains provide a mechanism for the subcellular targeting, as well as determining their substrate specificity and enzymatic activity. These hypotheses require additional investigations beyond my expertise in molecular biology. Specifically, there are four areas of career development that I have arranged over the course of the next five years. These include the identification of interacting proteins that form complexes with STEP members using both the yeast 2 hybrid system, as well as affinity chromatography to biochemically purify associated proteins. STEP knockout mice will also be characterized. The proposed investigations will be done in the supportive environment of the Child Study Center with its commitment to clinically informed basic science research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: TIME COURSE AND POTENTIATION OF FLUOXETIN ACTION Principal Investigator & Institution: Van De Kar, Louis D.; Professor; Pharmacol & Exper Therapeutics; Loyola University Medical Center Lewis Towers, 13Th Fl Chicago, Il 60611 Timing: Fiscal Year 2002; Project Start 14-JAN-2002; Project End 31-DEC-2004 Summary: (provided by applicant) The long-term goal of the proposed studies is to provide novel therapeutic approaches for the treatment of mood disorders that will work more rapidly and more effectively than the currently available medications. The introduction of selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine (Prozac) has revolutionized psychiatry. In addition to their effectiveness in the treatment of depression, SSRIs also have proven effective for the treatment of several mood disorders for which the older medications were ineffective. These disorders include anxiety, obsessive compulsive disorder, aggression, eating disorders and premenstrual syndrome. However, a lag time of about 2-3 weeks exists from the onset of medication until the first signs of improvement appear. This delayed onset of therapeutic effects is a severe problem. Some of the suicides of depressed patients occur during this lag time.

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Therefore, there is a great need to find therapeutic approaches that will work more rapidly. Studies supporting the parent grant indicate that treatment with SSRIs produces a delayed-onset, homologous desensitization of post-synaptic serotoninlA( 5HT1A) receptors in the hypothalamus. This desensitization is most likely mediated by increased levels of 5-HT in the synapse and the resulting over-activation of postsynaptic receptors. Studies in depressed patients indicate that the therapeutic effectiveness of SSRIs is dependent on maintaining high levels of 5-HT in the synaptic cleft. The 5-HT reuptake mechanism is the primary mechanism terminating the activation of post-synaptic receptors by 5-HT in the synaptic cleft. However, the release of 5-HT from the nerve terminals is highly regulated by inhibitory 5-HT1A autoreceptors on the soma and dendrites of the serotonergic cells in the raphe nuclei and by inhibitory 5-HT1B/1D autoreceptors on the serotonergic nerve terminals in forebrain regions. Thus, the overall hypothesis is that during SSRI therapy, the inhibitory influences of 5-HT autoreceptors must be overcome to allow SSRIs to increase the levels of 5-HT in the synaptic cleft. The proposed studies will use in vivo microdialysis approaches to investigate the time courses of changes in both 5-HT1A and 5-HT1B/1D autoreceptors, and thus determine whether these receptors contribute to the delay in onset of fluoxetine-induced increase in extracellular levels of 5-HT in several forebrain regions. In addition, the studies will investigate whether combining fluoxetine with selective 5-HT1A and/or 5-HT1B/1D antagonists will accelerate the fluoxetine-induced increase in extracellular levels of 5-HT. The results of the present studies will provide the scientific foundation for the use of specific autoreceptor antagonists as adjunctive therapy with SSRIs to produce a more rapid and effective therapy of mood disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TRACKING MULTIMODAL CHANGE IN CBT FOR CHILDHOOD OCD Principal Investigator & Institution: Langley, Audra K.; None; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2001; Project Start 14-SEP-2001 Summary: (provided by applicant): The proposed research will track and document specific treatment-related cognitive, physiological, and behavioral changes over time in children and adolescents participating in an ongoing RCT examining the efficacy of exposure-based CBT for childhood OCD (RO1 MH58459). The primary aim of the proposed research is to develop methodology to aid in tracking the timing, sequence, and nature of these changes in order to explore such relationships in response to a standard multicomponent treatment paradigm. Specifically, participants? cognitions/irrational beliefs and physiological responses (EMG, GSR, HR) will be assessed at baseline, weeks 4, 8, and 12 of treatment, and at 6 month follow-up. Additionally, patients will complete a Behavioral Avoidance Test based on 2 symptoms from their hierarchy at baseline, post-treatment, and 6-month follow-up. An examination of each of these factors will improve upon our ability to properly assess anxiety and anxiety-related changes in youth with Obsessive Compulsive Disorder in a multimodal fashion. Moreover, the current study will enhance our knowledge of the individual effectiveness of treatment components within this population. Taking advantage of a preexisting NIMH-funded multicomponent CBT study will provide an ideal and efficient opportunity for the proposed examination. Ultimately, results will be used to support the development of prospective studies examining individual and interactive effects of cognitive and behavioral techniques with the aim of identifying

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mechanisms of change as well as the possible benefit of providing prescriptive treatment for this developmentally diverse population. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TREATMENT OF COMPULSIVE HOARDING Principal Investigator & Institution: Steketee, Gail S.; Professor; None; Boston University Medical Campus 715 Albany St, 560 Boston, Ma 02118 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-MAY-2006 Summary: (provided by applicant): Compulsive hoarding, considered a form of obsessive-compulsive disorder (OCD), includes symptoms of excessive acquisition (buying, acquiring free things), difficulty discarding, and excessive clutter. It is resistant to both pharmacological (serotonergic medications) and psychotherapeutic interventions (exposure and response prevention) that have been demonstrated effective for other symptoms of OCD. The proposed project aims to develop and test a multicomponent psychosocial treatment based on identified psychopathology features of compulsive hoarding and on a cognitive behavioral model of this complex syndrome. It also aims to pilot test the manualized therapy to determine the effect size of the treatment based on comparison to waitlist control. A cognitive-behavioral treatment (CBT) manual investigators have employed in pilot studies of small samples will be revised and expanded in Phase 1, particularly with regard to elaboration of motivational and relapse prevention methods. In Phase 2, two therapists at research-based anxiety clinic settings in Boston and Hartford will be trained to use the revised manual to treat 12 clients for whom compulsive hoarding is their main problem. During this phase, treatment will be flexibly applied allowing for variations in treatment duration and choice of techniques within symptom-focused modules. Investigators will closely supervise therapists by listening to audiotapes of all treatment sessions. Measures of therapist adherence and competence developed in Phase 1 will be refined and tested by investigators in Phase 2. Process and outcome experience with clients during the second phase will guide further revisions to the manual and to adherence/competence measures, as well as the decision about the optimal length of treatment for a pilot study with a larger sample. In Phase 3, 40 clients with primary hoarding symptoms will be treated with a fixed duration therapy at the same two sites. Clients will be randomly assigned to CBT or to waitlist (WL) control followed by active treatment. Independent assessors will assess adherence and competence from audiotaped therapy sessions using revised instruments. Outcomes will be assessed with psychometrically sound measures of compulsive hoarding symptoms and related psychopathology to yield effect size estimates suitable for future large scale controlled trials. Predictors of outcome will be examined. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: DISORDER

TREATMENT

OF

PEDIATRIC

OBSESSIVE

COMPULSIVE

Principal Investigator & Institution: Foa, Edna B.; Professor; Psychiatry; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2001; Project Start 01-MAY-1997; Project End 31-OCT-2002 Summary: (Adapted from applicant's abstract): One in two hundred young suffers from Obsessive-Compulsive Disorder (OCD), yet relatively few receive appropriate treatment. Both cognitive-behavior therapy (CBT) and medication appear beneficial in controlled studies; however, the relative efficacy of CBT and medication, alone and in

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combination, (COMB), is unknown. Thus well-designed treatment outcome studies are necessary to improve care for youth with OCD. This revised proposal constitutes one half of a (two-center) Multi-Institutional Collaborative Research Project focused on the treatment of pediatric OCD, resubmitted jointly but separately by Drs. Edna Foa at Allegheny University (AU) and John March at Duke University. Using a volunteer sample of 120 (60/site) youth age 8-16 with a DSM-IV diagnosis of OCD, the proposed 5 year treatment outcome study contrasts the degree and durability of improvement obtained across six treatment conditions: 3 active treatments, sertraline alone (SER), OCD-specific behavior therapy (CBT), both SER and CBT (SER+CBT) and 3 control treatments, pill PBO, pill PBO+Educational Support (ES) and SER+ES. The experimental design covers 2 phases. Phase I is a 2 (site) x 2 (sertraline or pill PBO) x 3 (CBT, ES or non psychosocial treatment) x 5 (repeated measures) factorial 12 week comparison of SER, CBT, COMB and the control conditions. In Phase II, responders advance to a 16 week discontinuation study to assess treatment durability. The primary outcome measure is the Yale-Brown Obsessive-Compulsive Scale. Assessments blind to treatment status take place at week 0 (pretreatment); weeks 1, 4, 8, 12 (Phase I treatment); and weeks 16, 20, 24 and 28 (Phase II discontinuation). Besides addressing comparative efficacy and durability of the specified treatments, we also examine time-action effects, differential effects on specific aspects of OCD, including functional impairment, and predictors of response to treatment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TREATMENT OF PEDIATRIC OCD Principal Investigator & Institution: Franklin, Martin E.; Assistant Professor; Psychiatry; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2003; Project Start 01-MAY-1997; Project End 31-JUL-2008 Summary: (provided by applicant): This competing continuation proposal, Treatment of Pediatric OCD, addresses an important problem in the management of pediatric OCD, namely partial response to initial treatment with a serotonin reuptake inhibitor(SRI). For most pediatric OCD patients treated in the community, the first line initial treatment is monotherapy with an SRI. Recommended doses of these medications leave the great majority of patients with clinically significant residual symptoms. While OCD experts typically recommend augmenting SRI partial responders with cognitive-behavior therapy (CBT), this recommendation is seldom followed. An alternative augmentation strategy widely used in community practice but considered second-line by OCD experts is to add an atypical neuroleptic, such as risperidone (RIS), to SRI monotherapy. Because CBT and augmenting medications may differ in relative benefit and in risk, it is Imperative to conduct a well-controlled comparison of these two augmentation strategies against a control condition in the same patient population. The proposed study, which will be conducted at Duke University (John March), University of Pennsylvania (Martin Franklin) and Brown University (Henrietta Leonard), will meet this vital public health objective. Specifically, using a volunteer sample of 135 youth (45/site) age 8-17 with a primary DSM-IV diagnosis of OCD partially responsive to SRI pharmacotherapy, we propose to conduct a 5 year outcome study that will evaluate the relative efficacy of augmentation with: (1) OCD-specific CBT; (2) risperidone (RIS); and (3) pill placebo (PBO). We propose a balanced 3 (site) x 3 (CBT, RIS, or PBO) x 4 (assessment point) 12-week comparison of the three conditions. At study exit, all participants will be given clinical recommendations regarding further treatment based on their clinical status and will be followed up naturalistically for 12 additional months. PBO non-responders at the end of acute treatment will be given a choice of open

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treatment with either CBT or RIS delivered at no cost by the study team; non-responders to CBT or RIS will receive the alternative treatment delivered at no cost by the study team or, if they prefer, will be referred for community treatment. Blind assessments will be conducted for all patients at weeks 0, 4, 8, 12 (Phase I); the IE but not the patient will be blind for assessments during naturalistic follow-up, which will be conducted at 3, 6, 9 and 12 months post treatment. By examining the relative benefit and risk of CBT and RIS augmentation in the same patient population, the proposed study will provide an empirical basis for formulating practice guidelines. Health professionals then will be better able to advise their pediatric OCD patients regarding the management of partial response to SRls. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ZIPRASIDONE IN TOURETTES COMPULSIVE & PERVASIVE DEV. DISORDER

SYNDROME,

OBSESSIVE

Principal Investigator & Institution: Leckman, James F.; Nieson Harris Professor; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2001 Summary: The purpose of this study is evaluate the long-term effectiveness and safety of ziprasidone in the treatment of children and adults with Tourettes syndrome, Obsessive-Compulsive disorder, and Pervasive Development Disorder. Thirty (30) subjects (10 in each diagnosic group) will be enrolled in a one-year, open-label study. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

E-Journals: PubMed Central3 PubMed Central (PMC) is a digital archive of life sciences journal literature developed and managed by the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).4 Access to this growing archive of e-journals is free and unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, and type “obsessive compulsive disorder” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for obsessive compulsive disorder in the PubMed Central database: •

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Somatization in response to undiagnosed obsessive compulsive disorder in a family. by Weiss R, Fogelman Y, Yaphe J.; 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=150573

Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html.

With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age. 5 The value of PubMed Central, in addition to its role as an archive, lies in the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print.

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The National Library of Medicine: PubMed One of the quickest and most comprehensive ways to find academic studies in both English and other languages is to use PubMed, maintained by the National Library of Medicine.6 The advantage of PubMed over previously mentioned sources is that it covers a greater number of domestic and foreign references. It is also free to use. If the publisher has a Web site that offers full text of its journals, PubMed will provide links to that site, as well as to sites offering other related data. User registration, a subscription fee, or some other type of fee may be required to access the full text of articles in some journals. To generate your own bibliography of studies dealing with obsessive compulsive disorder, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “obsessive compulsive disorder” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for obsessive compulsive disorder (hyperlinks lead to article summaries): •

A behavioural approach to obsessive compulsive disorder. Author(s): Taylor E. Source: Nurs Times. 1998 May 6-12; 94(18): 56-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9633419&dopt=Abstract

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A comparative examination of a role for serotonin in obsessive compulsive disorder, panic disorder, and anxiety. Author(s): Murphy DL, Pigott TA. Source: The Journal of Clinical Psychiatry. 1990 April; 51 Suppl: 53-8; Discussion 59-60. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2139026&dopt=Abstract

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A flow cytometric assay for D8/17 B cell marker in patients with Tourette's syndrome and obsessive compulsive disorder. Author(s): Chapman F, Visvanathan K, Carreno-Manjarrez R, Zabriskie JB. Source: Journal of Immunological Methods. 1998 October 1; 219(1-2): 181-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9831399&dopt=Abstract

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A fluvoxamine-induced frontal lobe syndrome in a patient with comorbid Gilles de la Tourette's syndrome and obsessive compulsive disorder. Author(s): George MS, Trimble MR. Source: The Journal of Clinical Psychiatry. 1992 October; 53(10): 379-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1429480&dopt=Abstract

6 PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.

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A preliminary assessment of sensorimotor gating in patients with obsessive compulsive disorder. Author(s): Swerdlow NR, Benbow CH, Zisook S, Geyer MA, Braff DL. Source: Biological Psychiatry. 1993 February 15; 33(4): 298-301. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8471686&dopt=Abstract

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A preliminary investigation of the lifetime prevalence of anorexia and bulimia nervosa in patients with obsessive compulsive disorder. Author(s): Rubenstein CS, Pigott TA, L'Heureux F, Hill JL, Murphy DL. Source: The Journal of Clinical Psychiatry. 1992 September; 53(9): 309-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1517192&dopt=Abstract

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A randomized controlled trial of cognitive therapy versus intensive behavior therapy in obsessive compulsive disorder. Author(s): Cottraux J, Note I, Yao SN, Lafont S, Note B, Mollard E, Bouvard M, Sauteraud A, Bourgeois M, Dartigues JF. Source: Psychotherapy and Psychosomatics. 2001 November-December; 70(6): 288-97. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11598428&dopt=Abstract

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A Singapore study of obsessive compulsive disorder. Author(s): Chia BH. Source: Singapore Med J. 1996 August; 37(4): 402-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8993143&dopt=Abstract

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Aberrant snacking patterns and eating disorders in patients with obsessive compulsive disorder. Author(s): O'Rourke DA, Wurtman JJ, Wurtman RJ, Tsay R, Gleason R, Baer L, Jenike MA. Source: The Journal of Clinical Psychiatry. 1994 October; 55(10): 445-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7961522&dopt=Abstract

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Advances in understanding obsessive compulsive disorder. Author(s): Kelleher M. Source: Ir Med J. 1995 March-April; 88(2): 52, 55. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7775144&dopt=Abstract

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AIDS-related obsessive compulsive disorder: deconditioning based on fluoxetineinduced inhibition of anxiety. Author(s): Kraus RP, Nicholson IR. Source: Journal of Behavior Therapy and Experimental Psychiatry. 1996 March; 27(1): 51-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8814521&dopt=Abstract

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An analysis of response prevention and flooding procedures in the treatment of adolescent obsessive compulsive disorder. Author(s): Harris CV, Wiebe DJ. Source: Journal of Behavior Therapy and Experimental Psychiatry. 1992 June; 23(2): 10715. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1360985&dopt=Abstract

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An integrated approach to treatment of obsessive compulsive disorder. Author(s): Greist JH. Source: The Journal of Clinical Psychiatry. 1992 April; 53 Suppl: 38-41. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1532963&dopt=Abstract

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An open-label study of nefazodone in the treatment of depression with and without comorbid obsessive compulsive disorder. Author(s): Nelson EC. Source: Annals of Clinical Psychiatry : Official Journal of the American Academy of Clinical Psychiatrists. 1994 December; 6(4): 249-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7647834&dopt=Abstract

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Animal models in obsessive compulsive disorder. Author(s): Olivier B. Source: International Clinical Psychopharmacology. 1992 June; 7 Suppl 1: 27-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1517553&dopt=Abstract

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Antidepressant induced mania in obsessive compulsive disorder. Author(s): Berk M, Koopowitz LF, Szabo CP. Source: European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology. 1996 March; 6(1): 9-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8866932&dopt=Abstract

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Anxiety disorders and obsessive compulsive disorder. Author(s): Liebowitz MR. Source: Neuropsychobiology. 1998; 37(2): 69-71. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9566268&dopt=Abstract

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Are the eating disorders related to obsessive compulsive disorder? Author(s): Hsu LK, Kaye W, Weltzin T. Source: The International Journal of Eating Disorders. 1993 November; 14(3): 305-18. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8275067&dopt=Abstract

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Assessment of severity and change in obsessive compulsive disorder. Author(s): Goodman WK, Price LH. Source: The Psychiatric Clinics of North America. 1992 December; 15(4): 861-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1461801&dopt=Abstract

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Association between homozygosity at the COMT gene locus and obsessive compulsive disorder. Author(s): Schindler KM, Richter MA, Kennedy JL, Pato MT, Pato CN. Source: American Journal of Medical Genetics. 2000 December 4; 96(6): 721-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11121168&dopt=Abstract

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Behavior therapy for obsessive compulsive disorder in the office-based practice. Author(s): Baer L. Source: The Journal of Clinical Psychiatry. 1993 June; 54 Suppl: 10-5; Discussion 30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8331097&dopt=Abstract

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Behavior therapy for obsessive compulsive disorder. Author(s): Greist JH. Source: The Journal of Clinical Psychiatry. 1994 October; 55 Suppl: 60-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7961534&dopt=Abstract

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Behavior therapy for obsessive compulsive disorder. Author(s): Dar R, Greist JH. Source: The Psychiatric Clinics of North America. 1992 December; 15(4): 885-94. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1461803&dopt=Abstract

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Behavioral avoidance test for obsessive compulsive disorder. Author(s): Steketee G, Chambless DL, Tran GQ, Worden H, Gillis MM. Source: Behaviour Research and Therapy. 1996 January; 34(1): 73-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8561767&dopt=Abstract

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Behavioral versus pharmacological treatments of obsessive compulsive disorder: a meta-analysis. Author(s): Kobak KA, Greist JH, Jefferson JW, Katzelnick DJ, Henk HJ. Source: Psychopharmacology. 1998 April; 136(3): 205-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9566805&dopt=Abstract

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Behaviour therapy for obsessive compulsive disorder in a 78-year-old woman. Author(s): Colvin C, Boddington SJ. Source: International Journal of Geriatric Psychiatry. 1997 April; 12(4): 488-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9178056&dopt=Abstract

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Beyond the serotonin hypothesis: a role for dopamine in some forms of obsessive compulsive disorder? Author(s): Goodman WK, McDougle CJ, Price LH, Riddle MA, Pauls DL, Leckman JF. Source: The Journal of Clinical Psychiatry. 1990 August; 51 Suppl: 36-43; Discussion 558. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2199433&dopt=Abstract

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Biological approaches to treatment-resistant obsessive compulsive disorder. Author(s): Goodman WK, McDougle CJ, Barr LC, Aronson SC, Price LH. Source: The Journal of Clinical Psychiatry. 1993 June; 54 Suppl: 16-26. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8331098&dopt=Abstract

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Buspirone augmentation of fluoxetine in patients with obsessive compulsive disorder. Author(s): Jenike MA, Baer L, Buttolph L. Source: The Journal of Clinical Psychiatry. 1991 January; 52(1): 13-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1988411&dopt=Abstract

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Case series: Adderall augmentation of serotonin reuptake inhibitors in childhoodonset obsessive compulsive disorder. Author(s): Owley T, Owley S, Leventhal B, Cook EH Jr. Source: Journal of Child and Adolescent Psychopharmacology. 2002 Summer; 12(2): 16571. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12188985&dopt=Abstract

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Cerebral metabolic correlates as potential predictors of response to anterior cingulotomy for obsessive compulsive disorder. Author(s): Rauch SL, Dougherty DD, Cosgrove GR, Cassem EH, Alpert NM, Price BH, Nierenberg AA, Mayberg HS, Baer L, Jenike MA, Fischman AJ. Source: Biological Psychiatry. 2001 November 1; 50(9): 659-67. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11704072&dopt=Abstract

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Cerebrospinal fluid biogenic amines in obsessive compulsive disorder, Tourette's syndrome, and healthy controls. Author(s): Leckman JF, Goodman WK, Anderson GM, Riddle MA, Chappell PB, McSwiggan-Hardin MT, McDougle CJ, Scahill LD, Ort SI, Pauls DL, et al. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 1995 February; 12(1): 73-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7766289&dopt=Abstract

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Checkers and washers: valid subtypes of obsessive compulsive disorder. Author(s): Khanna S, Mukherjee D. Source: Psychopathology. 1992; 25(5): 283-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1293628&dopt=Abstract

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Childhood movement disorders and obsessive compulsive disorder. Author(s): Swedo SE, Leonard HL. Source: The Journal of Clinical Psychiatry. 1994 March; 55 Suppl: 32-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7915713&dopt=Abstract

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Childhood obsessive compulsive disorder. Author(s): Rapoport JL, Swedo SE, Leonard HL. Source: The Journal of Clinical Psychiatry. 1992 April; 53 Suppl: 11-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1564053&dopt=Abstract

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Childhood onset obsessive compulsive disorder: is there a unique subtype? Author(s): Leonard H. Source: Medicine and Health, Rhode Island. 1999 April; 82(4): 122. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10228336&dopt=Abstract

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Childhood-onset obsessive compulsive disorder. Author(s): Swedo SE, Leonard HL, Rapoport JL. Source: The Psychiatric Clinics of North America. 1992 December; 15(4): 767-75. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1461794&dopt=Abstract

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Children with obsessive compulsive disorder. Author(s): Heyman I. Source: Bmj (Clinical Research Ed.). 1997 August 23; 315(7106): 444. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9284654&dopt=Abstract

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Circulating lymphocyte subsets in obsessive compulsive disorder, major depression and normal controls. Author(s): Ravindran AV, Griffiths J, Merali Z, Anisman H. Source: Journal of Affective Disorders. 1999 January-March; 52(1-3): 1-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10357012&dopt=Abstract

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Clinical correlates of obsessive compulsive disorder in children and adolescents referred to specialized and non-specialized clinical settings. Author(s): Geller D, Biederman J, Faraone SV, Frazier J, Coffey BJ, Kim G, Bellordre CA. Source: Depression and Anxiety. 2000; 11(4): 163-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10945136&dopt=Abstract

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Clomipramine and obsessive compulsive disorder: a placebo-controlled double-blind study of 32 patients. Author(s): Greist JH, Jefferson JW, Rosenfeld R, Gutzmann LD, March JS, Barklage NE. Source: The Journal of Clinical Psychiatry. 1990 July; 51(7): 292-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2195006&dopt=Abstract

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Clomipramine in obsessive compulsive disorder. Author(s): Lee S. Source: The Journal of Clinical Psychiatry. 1991 April; 52(4): 183-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2016256&dopt=Abstract

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Clomipramine: a tricyclic antidepressant effective in obsessive compulsive disorder. Author(s): Kelly MW, Myers CW. Source: Dicp. 1990 July-August; 24(7-8): 739-44. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2197816&dopt=Abstract

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Clomipramine-resistant, fluoxetine-responsive obsessive compulsive disorder: a case report. Author(s): Paholpak S. Source: J Med Assoc Thai. 2002 October; 85(10): 1135-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12501907&dopt=Abstract

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Clonazepam treatment of obsessive compulsive disorder. Author(s): Bacher NM. Source: The Journal of Clinical Psychiatry. 1990 April; 51(4): 168-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2324082&dopt=Abstract

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Cognitive and behavioral therapies alone versus in combination with fluvoxamine in the treatment of obsessive compulsive disorder. Author(s): van Balkom AJ, de Haan E, van Oppen P, Spinhoven P, Hoogduin KA, van Dyck R. Source: The Journal of Nervous and Mental Disease. 1998 August; 186(8): 492-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9717867&dopt=Abstract

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Cognitive therapy and exposure in vivo in the treatment of obsessive compulsive disorder. Author(s): van Oppen P, de Haan E, van Balkom AJ, Spinhoven P, Hoogduin K, van Dyck R. Source: Behaviour Research and Therapy. 1995 May; 33(4): 379-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7755525&dopt=Abstract

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Comorbid obsessive compulsive and major depressive disorder. Author(s): Ninan PT. Source: Psychopharmacology Bulletin. 2001 Winter; 35(1): 77-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12397872&dopt=Abstract

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Comorbidity of obsessive compulsive disorder in bipolar disorder. Author(s): Kruger S, Cooke RG, Hasey GM, Jorna T, Persad E. Source: Journal of Affective Disorders. 1995 May 17; 34(2): 117-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7665803&dopt=Abstract

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Comorbidity of obsessive compulsive disorder in patients with eating disorders. Author(s): Lennkh C, Strnad A, Bailer U, Biener D, Fodor G, de Zwaan M. Source: Eat Weight Disord. 1998 March; 3(1): 37-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11234253&dopt=Abstract

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Comparison of obsessions and compulsions in patients with anorexia nervosa and obsessive compulsive disorder. Author(s): Bastiani AM, Altemus M, Pigott TA, Rubenstein C, Weltzin TE, Kaye WH. Source: Biological Psychiatry. 1996 June 1; 39(11): 966-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9162209&dopt=Abstract

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Complex segregation analysis for obsessive compulsive disorder and related disorders. Author(s): Cavallini MC, Pasquale L, Bellodi L, Smeraldi E. Source: American Journal of Medical Genetics. 1999 February 5; 88(1): 38-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10050965&dopt=Abstract

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Conditioned blocking in patients with paranoid, non-paranoid psychosis or obsessive compulsive disorder: associations with symptoms, personality and monoamine metabolism. Author(s): Oades RD, Zimmermann B, Eggers C. Source: Journal of Psychiatric Research. 1996 September-October; 30(5): 369-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8923341&dopt=Abstract

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Corpus callosal morphology in treatment-naive pediatric obsessive compulsive disorder. Author(s): Rosenberg DR, Keshavan MS, Dick EL, Bagwell WW, MacMaster FP, Birmaher B. Source: Progress in Neuro-Psychopharmacology & Biological Psychiatry. 1997 November; 21(8): 1269-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9460091&dopt=Abstract

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Corticotropin releasing factor stimulation test in obsessive compulsive disorder. Author(s): Bailly D, Servant D, Dewailly D, Beuscart R, Racadot A, Fossati P, Parquet PJ. Source: Biological Psychiatry. 1994 January 15; 35(2): 143-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8167212&dopt=Abstract

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Current issues in the pharmacologic management of obsessive compulsive disorder. Author(s): Rasmussen SA, Eisen JL, Pato MT. Source: The Journal of Clinical Psychiatry. 1993 June; 54 Suppl: 4-9. Review. Erratum In: J Clin Psychiatry 1993 December; 54(12): 491. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8101187&dopt=Abstract

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Decision making performance in obsessive compulsive disorder. Author(s): Nielen MM, Veltman DJ, de Jong R, Mulder G, den Boer JA. Source: Journal of Affective Disorders. 2002 May; 69(1-3): 257-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12103475&dopt=Abstract

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Depression and suicidal behavior in adolescent inpatients with obsessive compulsive disorder. Author(s): Apter A, Horesh N, Gothelf D, Zalsman G, Erlich Z, Soreni N, Weizman A. Source: Journal of Affective Disorders. 2003 July; 75(2): 181-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12798258&dopt=Abstract

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Developmental aspects of obsessive compulsive disorder: findings in children, adolescents, and adults. Author(s): Geller DA, Biederman J, Faraone S, Agranat A, Cradock K, Hagermoser L, Kim G, Frazier J, Coffey BJ. Source: The Journal of Nervous and Mental Disease. 2001 July; 189(7): 471-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11504325&dopt=Abstract

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Diagnosis and treatment of obsessive compulsive disorder. Author(s): DeVeaugh-Geiss J. Source: Annual Review of Medicine. 1993; 44: 53-61. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8476267&dopt=Abstract

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Disturbed monitoring and response inhibition in patients with Gilles de la Tourette syndrome and co-morbid obsessive compulsive disorder. Author(s): Muller SV, Johannes S, Wieringa B, Weber A, Muller-Vahl K, Matzke M, Kolbe H, Dengler R, Munte TF. Source: Behavioural Neurology. 2003; 14(1-2): 29-37. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12719636&dopt=Abstract

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Does melatonin mediate the therapeutic effects of 5-HT reuptake inhibitors in obsessive compulsive disorder? Author(s): Sandyk R. Source: The International Journal of Neuroscience. 1992 May-June; 64(1-4): 221-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1342043&dopt=Abstract

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Dopamine antagonists in tic-related and psychotic spectrum obsessive compulsive disorder. Author(s): McDougle CJ, Goodman WK, Price LH. Source: The Journal of Clinical Psychiatry. 1994 March; 55 Suppl: 24-31. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7521326&dopt=Abstract

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Dopamine function in obsessive compulsive disorder: cortisol response to acute apomorphine stimulation. Author(s): Brambilla F, Perna G, Bussi R, Bellodi L. Source: Psychoneuroendocrinology. 2000 April; 25(3): 301-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10737700&dopt=Abstract

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Double-blind comparison of fluoxetine versus clomipramine in the treatment of obsessive compulsive disorder. Author(s): Lopez-Ibor JJ Jr, Saiz J, Cottraux J, Note I, Vinas R, Bourgeois M, Hernandez M, Gomez-Perez JC. Source: European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology. 1996 May; 6(2): 111-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8791036&dopt=Abstract

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Eating disorder history in women with obsessive compulsive disorder. Author(s): Tamburrino MB, Kaufman R, Hertzer J. Source: J Am Med Womens Assoc. 1994 January-February; 49(1): 24-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8138642&dopt=Abstract

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Elevated cerebrospinal fluid corticotropin-releasing factor in Tourette's syndrome: comparison to obsessive compulsive disorder and normal controls. Author(s): Chappell P, Leckman J, Goodman W, Bissette G, Pauls D, Anderson G, Riddle M, Scahill L, McDougle C, Cohen D. Source: Biological Psychiatry. 1996 May 1; 39(9): 776-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8731518&dopt=Abstract

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Evidence for linkage disequilibrium between serotonin transporter protein gene (SLC6A4) and obsessive compulsive disorder. Author(s): McDougle CJ, Epperson CN, Price LH, Gelernter J. Source: Molecular Psychiatry. 1998 May; 3(3): 270-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9672904&dopt=Abstract

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Exposure with response prevention and serotonergic antidepressants in the treatment of obsessive compulsive disorder: a review and implications for interdisciplinary treatment. Author(s): Abel JL. Source: Behaviour Research and Therapy. 1993 June; 31(5): 463-78. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8101439&dopt=Abstract

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Factor analysis of symptom subtypes of obsessive compulsive disorder and their relation to personality and tic disorders. Author(s): Baer L. Source: The Journal of Clinical Psychiatry. 1994 March; 55 Suppl: 18-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8077163&dopt=Abstract

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FDG-PET predictors of response to behavioral therapy and pharmacotherapy in obsessive compulsive disorder. Author(s): Brody AL, Saxena S, Schwartz JM, Stoessel PW, Maidment K, Phelps ME, Baxter LR Jr. Source: Psychiatry Research. 1998 November 9; 84(1): 1-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9870412&dopt=Abstract

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Fenfluramine augmentation of clomipramine treatment of obsessive compulsive disorder. Author(s): Judd FK, Chua P, Lynch C, Norman T. Source: The Australian and New Zealand Journal of Psychiatry. 1991 September; 25(3): 412-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1958165&dopt=Abstract

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Fluoxetine in obsessive compulsive disorder in adolescents. Author(s): Bouvard M, Dugas M. Source: International Clinical Psychopharmacology. 1993 Winter; 8(4): 307-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8277152&dopt=Abstract

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Fluoxetine, but not tricyclic antidepressants, potentiates the 5-hydroxytryptophanmediated increase in plasma cortisol and prolactin secretion in subjects with major depression or with obsessive compulsive disorder. Author(s): Meltzer H, Bastani B, Jayathilake K, Maes M. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 1997 July; 17(1): 1-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9194044&dopt=Abstract

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Fluvoxamine in the treatment of obsessive compulsive disorder. Author(s): Montgomery SA, Manceaux A. Source: International Clinical Psychopharmacology. 1992 June; 7 Suppl 1: 5-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1355499&dopt=Abstract

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Fluvoxamine versus clomipramine in the treatment of obsessive compulsive disorder: a multicenter, randomized, double-blind, parallel group comparison. Author(s): J Am Acad Child Adolesc Psychiatry. 1995 Feb;34(2):128-9 Source: The Journal of Clinical Psychiatry. 1994 July; 55(7): 301-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7896644

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fMRI of neuronal activation with symptom provocation in unmedicated patients with obsessive compulsive disorder. Author(s): Adler CM, McDonough-Ryan P, Sax KW, Holland SK, Arndt S, Strakowski SM. Source: Journal of Psychiatric Research. 2000 July-October; 34(4-5): 317-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11104844&dopt=Abstract

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Friday the 13th and obsessive compulsive disorder. Author(s): Veale D. Source: Bmj (Clinical Research Ed.). 1995 October 14; 311(7011): 963-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7580624&dopt=Abstract

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Fusion or confusion in obsessive compulsive disorder. Author(s): O'Connor K, Aardema F. Source: Psychological Reports. 2003 August; 93(1): 227-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14563054&dopt=Abstract

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Gender differences in obsessive compulsive disorder. Author(s): Castle DJ, Deale A, Marks IM. Source: The Australian and New Zealand Journal of Psychiatry. 1995 March; 29(1): 1147. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7625960&dopt=Abstract

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Gender identity disorder presenting in a girl with Asperger's disorder and obsessive compulsive disorder. Author(s): Perera H, Gadambanathan T, Weerasiri S. Source: Ceylon Med J. 2003 June; 48(2): 57-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12971211&dopt=Abstract

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Group and multifamily behavioral treatment for obsessive compulsive disorder: a pilot study. Author(s): Van Noppen B, Steketee G, McCorkle BH, Pato M. Source: Journal of Anxiety Disorders. 1997 July-August; 11(4): 431-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9276786&dopt=Abstract

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Hoarding in obsessive compulsive disorder: results from a case-control study. Author(s): Samuels J, Bienvenu OJ 3rd, Riddle MA, Cullen BA, Grados MA, Liang KY, Hoehn-Saric R, Nestadt G. Source: Behaviour Research and Therapy. 2002 May; 40(5): 517-28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12043707&dopt=Abstract

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Hypochondriasis and obsessive compulsive disorder. Author(s): Barsky AJ. Source: The Psychiatric Clinics of North America. 1992 December; 15(4): 791-801. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1461796&dopt=Abstract

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Hypochondriasis and obsessive compulsive disorder: overlaps in diagnosis and treatment. Author(s): Fallon BA, Javitch JA, Hollander E, Liebowitz MR. Source: The Journal of Clinical Psychiatry. 1991 November; 52(11): 457-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1744062&dopt=Abstract

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Hypothalamic digoxin deficiency in obsessive compulsive disorder and la Tourette's syndrome. Author(s): Kurup RK, Kurup PA. Source: The International Journal of Neuroscience. 2002 July; 112(7): 797-816. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12424821&dopt=Abstract

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Inflated responsibility in obsessive compulsive disorder: validation of an operational definition. Author(s): Rheaume J, Ladouceur R, Freeston MH, Letarte H. Source: Behaviour Research and Therapy. 1995 February; 33(2): 159-69. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7887874&dopt=Abstract

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Inpatient treatment of obsessive compulsive disorder in childhood: a case study. Author(s): Scahill L, Walker RD, Lechner SN, Tynan KE. Source: J Child Adolesc Psychiatr Ment Health Nurs. 1993 July-September; 6(3): 5-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8106978&dopt=Abstract

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Is episodic obsessive compulsive disorder bipolar? A report of four cases. Author(s): Swartz CM, Shen WW. Source: Journal of Affective Disorders. 1999 November; 56(1): 61-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10626781&dopt=Abstract

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Is there a common mechanism of serotonin dysregulation in anorexia nervosa and obsessive compulsive disorder? Author(s): Barbarich N. Source: Eat Weight Disord. 2002 September; 7(3): 221-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12452254&dopt=Abstract

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Late local and remote structural changes after capsulotomy for obsessive compulsive disorder. Author(s): Taren JA, Curtis GC, Gebarski SS. Source: Stereotactic and Functional Neurosurgery. 1994; 63(1-4): 1-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7624620&dopt=Abstract

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Management of obsessive compulsive disorder. Author(s): Yap HL. Source: Singapore Med J. 1995 February; 36(1): 77-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7570142&dopt=Abstract

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Management of treatment-refractory obsessive compulsive disorder patients. Author(s): Dominguez RA, Mestre SM. Source: The Journal of Clinical Psychiatry. 1994 October; 55 Suppl: 86-92. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7961537&dopt=Abstract

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Managing the patient with treatment-resistant obsessive compulsive disorder: current strategies. Author(s): Jenike MA, Rauch SL. Source: The Journal of Clinical Psychiatry. 1994 March; 55 Suppl: 11-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7915709&dopt=Abstract

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Memory and confidence in memory judgements among individuals with obsessive compulsive disorder and non-clinical controls. Author(s): MacDonald PA, Antony MM, Macleod CM, Richter MA. Source: Behaviour Research and Therapy. 1997 June; 35(6): 497-505. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9159973&dopt=Abstract

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Monoamine activity reflected in urine of young patients with obsessive compulsive disorder, psychosis with and without reality distortion and healthy subjects: an explorative analysis. Author(s): Oades RD, Ropcke B, Eggers C. Source: Journal of Neural Transmission. General Section. 1994; 96(2): 143-59. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7857597&dopt=Abstract

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My battle with obsessive compulsive disorder. Author(s): Yaremichuk P. Source: Aarn News Lett. 1998 May; 54(5): 8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10594987&dopt=Abstract

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Naloxone-induced pituitary-adrenal activation does not differ in patients with depression, obsessive compulsive disorder, and healthy controls. Author(s): Michelson D, Altemus M, Galliven E, Hill L, Greenberg BD, Gold P. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 1996 August; 15(2): 207-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8840357&dopt=Abstract

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Naturalistic course of obsessive compulsive disorder and comorbid depression. Longitudinal results of a prospective follow-up study of 74 actively treated patients. Author(s): Zitterl W, Demal U, Aigner M, Lenz G, Urban C, Zapotoczky HG, ZitterlEglseer K. Source: Psychopathology. 2000 March-April; 33(2): 75-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10705250&dopt=Abstract

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Neurobiology of obsessive compulsive disorder. Author(s): Wright M, Hewlett WA. Source: Compr Ther. 1994; 20(2): 95-100. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7911407&dopt=Abstract

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Neurobiology of obsessive compulsive disorder. Author(s): Insel TR, Winslow JT. Source: The Psychiatric Clinics of North America. 1992 December; 15(4): 813-24. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1461798&dopt=Abstract

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Neurobiology of obsessive compulsive disorder: a possible role for serotonin. Author(s): Winslow JT, Insel TR. Source: The Journal of Clinical Psychiatry. 1990 August; 51 Suppl: 27-31; Discussion 558. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2199432&dopt=Abstract

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Neurobiology of obsessive compulsive disorder: a review. Author(s): Insel TR. Source: International Clinical Psychopharmacology. 1992 June; 7 Suppl 1: 31-3. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1517554&dopt=Abstract

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Neurobiology of obsessive compulsive disorder--a serotonergic basis of Freudian repression. Author(s): Katz RJ. Source: Neuroscience and Biobehavioral Reviews. 1991 Fall; 15(3): 375-81. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1956605&dopt=Abstract

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Neuroendocrine responses to intravenous L-tryptophan in obsessive compulsive disorder. Author(s): Fineberg NA, Cowen PJ, Kirk JW, Montgomery SA. Source: Journal of Affective Disorders. 1994 October; 32(2): 97-104. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7829769&dopt=Abstract

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Neuroimaging studies of obsessive compulsive disorder. Author(s): Baxter LR Jr. Source: The Psychiatric Clinics of North America. 1992 December; 15(4): 871-84. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1461802&dopt=Abstract

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Neurological and neuropsychological signs in obsessive compulsive disorder: interaction with behavioural treatment. Author(s): Bolton D, Raven P, Madronal-Luque R, Marks IM. Source: Behaviour Research and Therapy. 2000 July; 38(7): 695-708. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10875191&dopt=Abstract

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Neurosurgical treatment of malignant obsessive compulsive disorder. Author(s): Mindus, Jenike MA. Source: The Psychiatric Clinics of North America. 1992 December; 15(4): 921-38. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1461805&dopt=Abstract

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New pharmacologic approaches to obsessive compulsive disorder. Author(s): Insel TR. Source: The Journal of Clinical Psychiatry. 1990 October; 51 Suppl: 47-51; Discussion 568. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2120204&dopt=Abstract

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Noradrenergic receptor sensitivity in obsessive compulsive disorder: II. Cortisol response to acute clonidine administration. Author(s): Brambilla F, Bellodi L, Perna G, Arancio C, Bertani A, Perini G, Carraro C, Gava F. Source: Psychiatry Research. 1997 March 24; 69(2-3): 163-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9109184&dopt=Abstract

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Normal and abnormal information processing. A neuropsychological perspective on obsessive compulsive disorder. Author(s): Otto MW. Source: The Psychiatric Clinics of North America. 1992 December; 15(4): 825-48. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1461799&dopt=Abstract

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Obsessive compulsive disorder among idiopathic focal dystonia patients: an epidemiological and family study. Author(s): Cavallaro R, Galardi G, Cavallini MC, Henin M, Amodio S, Bellodi L, Comi G. Source: Biological Psychiatry. 2002 August 15; 52(4): 356-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12208643&dopt=Abstract

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Obsessive compulsive disorder and basal ganglia dysfunction. Author(s): Rapoport JL. Source: Psychological Medicine. 1990 August; 20(3): 465-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2236357&dopt=Abstract

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Obsessive compulsive disorder and depression--first results of a prospective study on 74 patients. Author(s): Demal U, Zitterl W, Lenz G, Zapotoczky HG, Zitterl-Eglseer K. Source: Progress in Neuro-Psychopharmacology & Biological Psychiatry. 1996 July; 20(5): 801-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8870065&dopt=Abstract

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Obsessive compulsive disorder and mood disorders: a family study. Author(s): Sciuto G, Pasquale L, Bellodi L. Source: American Journal of Medical Genetics. 1995 December 18; 60(6): 475-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8825883&dopt=Abstract

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Obsessive compulsive disorder and other disorders. Author(s): Lopez-Ibor JJ Jr. Source: International Clinical Psychopharmacology. 1992 June; 7 Suppl 1: 25-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1517552&dopt=Abstract

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Obsessive compulsive disorder and the right hemisphere: topographic analysis of lesions after anterior capsulotomy performed with thermocoagulation. Author(s): Lippitz B, Mindus P, Meyerson BA, Kihlstrom L, Lindquist C. Source: Acta Neurochir Suppl (Wien). 1997; 68: 61-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9233415&dopt=Abstract

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Obsessive compulsive disorder following head injury. Author(s): Ko SM. Source: Int J Clin Pract. 1997 July-August; 51(5): 336-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9489101&dopt=Abstract

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Obsessive compulsive disorder following left middle cerebral artery infarct. Author(s): Mahendran R. Source: Singapore Med J. 2000 October; 41(10): 498-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11281442&dopt=Abstract

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Obsessive compulsive disorder in childhood. Author(s): Carter AS, Pollock RA. Source: Current Opinion in Pediatrics. 2000 August; 12(4): 325-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10943811&dopt=Abstract

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Obsessive compulsive disorder in children and adolescents. Author(s): Jensen JB. Source: Current Opinion in Pediatrics. 1993 August; 5(4): 425-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8374668&dopt=Abstract

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Obsessive compulsive disorder in children and adolescents: issues in management. Author(s): Rapoport JL, Leonard HL, Swedo SE, Lenane MC. Source: The Journal of Clinical Psychiatry. 1993 June; 54 Suppl: 27-9; Discussion 30. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8331099&dopt=Abstract

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Obsessive compulsive disorder in children and adolescents: phenomenology and family history. Author(s): Riddle MA, Scahill L, King R, Hardin MT, Towbin KE, Ort SI, Leckman JF, Cohen DJ. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 1990 September; 29(5): 766-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2228931&dopt=Abstract

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Obsessive compulsive disorder in huntington disease: a case of isolated obsessions successfully treated with sertraline. Author(s): Patzold T, Brune M. Source: Neuropsychiatry, Neuropsychology, and Behavioral Neurology. 2002 September; 15(3): 216-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12218715&dopt=Abstract

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Obsessive compulsive disorder in primary care. Author(s): Shahady EJ. Source: The Journal of Clinical Psychiatry. 1994 October; 55 Suppl: 79-82; Discussion 835. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7961536&dopt=Abstract

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Obsessive compulsive disorder in ultra-orthodox Jewish patients: a comparison of religious and non-religious symptoms. Author(s): Greenberg D, Shefler G. Source: Psychology and Psychotherapy. 2002 June; 75(Pt 2): 123-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12396759&dopt=Abstract

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Obsessive compulsive disorder is not an anxiety disorder. Author(s): Montgomery SA. Source: International Clinical Psychopharmacology. 1993 September; 8 Suppl 1: 57-62. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8254154&dopt=Abstract

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Obsessive compulsive disorder manifesting as demonic attack. Author(s): Lacy TJ, Khatain KG. Source: The Journal of Clinical Psychiatry. 1993 October; 54(10): 398. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8262885&dopt=Abstract

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Obsessive compulsive disorder with psychotic features. Author(s): Eisen JL, Rasmussen SA. Source: The Journal of Clinical Psychiatry. 1993 October; 54(10): 373-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8262879&dopt=Abstract

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Obsessive compulsive disorder, checking, and non-verbal memory: a neuropsychological investigation. Author(s): Tallis F, Pratt P, Jamani N. Source: Behaviour Research and Therapy. 1999 February; 37(2): 161-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9990747&dopt=Abstract

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Obsessive compulsive disorder, depression, and fluoxetine. Author(s): Hollander E, Mullen L, DeCaria CM, Skodol A, Schneier FR, Liebowitz MR, Klein DF. Source: The Journal of Clinical Psychiatry. 1991 October; 52(10): 418-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1938978&dopt=Abstract

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Obsessive compulsive disorder, response to serotonin reuptake inhibitors and the serotonin transporter gene. Author(s): Billett EA, Richter MA, King N, Heils A, Lesch KP, Kennedy JL. Source: Molecular Psychiatry. 1997 September; 2(5): 403-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9322235&dopt=Abstract

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Obsessive compulsive disorder. Author(s): Soomro GM. Source: Clin Evid. 2002 June; (7): 896-905. Review. No Abstract Available. Update In: http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12230713&dopt=Abstract

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Obsessive compulsive disorder. Author(s): Clark L. Source: Can Fam Physician. 1999 August; 45: 1939-40. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10463095&dopt=Abstract

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Obsessive compulsive disorder. Author(s): Gordon J. Source: Aust Fam Physician. 1993 June; 22(6): 957-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8338467&dopt=Abstract

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Obsessive compulsive disorder. An update. Author(s): Jefferys D. Source: Aust Fam Physician. 1993 April; 22(4): 481-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8481111&dopt=Abstract

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Obsessive compulsive disorder: a case report. Author(s): Herren C, Lindroth J. Source: The Journal of Contemporary Dental Practice [electronic Resource]. 2001 August 15; 2(3): 41-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12167926&dopt=Abstract

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Obsessive compulsive disorder: a clinical update. Author(s): Black JL. Source: Mayo Clinic Proceedings. 1992 March; 67(3): 266-75. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1545595&dopt=Abstract

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Obsessive compulsive disorder: comorbid conditions. Author(s): Pigott TA, L'Heureux F, Dubbert B, Bernstein S, Murphy DL. Source: The Journal of Clinical Psychiatry. 1994 October; 55 Suppl: 15-27; Discussion 2832. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7961529&dopt=Abstract

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Obsessive compulsive disorder: is there an association with childhood streptococcal infections and altered immune function? Author(s): Murphy TK, Petitto JM, Voeller KK, Goodman WK. Source: Semin Clin Neuropsychiatry. 2001 October; 6(4): 266-76. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11607922&dopt=Abstract

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Obsessive compulsive disorder: nature and treatment. Author(s): Gournay K. Source: Nursing Standard : Official Newspaper of the Royal College of Nursing. 1998 November 25-December 1; 13(10): 46-52; Quiz 53-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9987405&dopt=Abstract

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Obsessive compulsive disorder: report of six cases. Author(s): Ovuga E. Source: East Afr Med J. 2001 May; 78(5): 269-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12002090&dopt=Abstract

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Obsessive compulsive disorder: serotonin and beyond. Author(s): Zohar J, Chopra M, Sasson Y, Amiaz R, Amital D. Source: World J Biol Psychiatry. 2000 April; 1(2): 92-100. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12607204&dopt=Abstract

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Obsessive compulsive disorder--a neuropsychiatric illness. Author(s): Ko SM. Source: Singapore Med J. 1996 April; 37(2): 186-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8942261&dopt=Abstract

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Obsessive compulsive symptoms in Gilles de la Tourette syndrome and obsessive compulsive disorder: differences by diagnosis and family history. Author(s): Eapen V, Robertson MM, Alsobrook JP 2nd, Pauls DL. Source: American Journal of Medical Genetics. 1997 July 25; 74(4): 432-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9259380&dopt=Abstract

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Olfactory sensitivity in major depressive disorder and obsessive compulsive disorder. Author(s): Gross-Isseroff R, Luca-Haimovici K, Sasson Y, Kindler S, Kotler M, Zohar J. Source: Biological Psychiatry. 1994 May 15; 35(10): 798-802. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8043710&dopt=Abstract

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On the role of prefrontal cortex glutamate for the antithetical phenomenology of obsessive compulsive disorder and attention deficit hyperactivity disorder. Author(s): Carlsson ML. Source: Progress in Neuro-Psychopharmacology & Biological Psychiatry. 2001 January; 25(1): 5-26. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11263758&dopt=Abstract

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Oxytocin in obsessive compulsive disorder. Author(s): den Boer JA, Westenberg HG. Source: Peptides. 1992 November-December; 13(6): 1083-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1494489&dopt=Abstract

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Panic and phobic disorders in patients with obsessive compulsive disorder. Author(s): Austin LS, Lydiard RB, Fossey MD, Zealberg JJ, Laraia MT, Ballenger JC. Source: The Journal of Clinical Psychiatry. 1990 November; 51(11): 456-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2228980&dopt=Abstract

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Panic disorder and obsessive compulsive disorder in a hyperventilation challenge test. Author(s): Nardi AE, Valenca AM, Nascimento I, Zin WA. Source: Journal of Affective Disorders. 2002 April; 68(2-3): 335-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12063161&dopt=Abstract

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Pentagastrin has panic-inducing properties in obsessive compulsive disorder. Author(s): de Leeuw AS, Den Boer JA, Slaap BR, Westenberg HG. Source: Psychopharmacology. 1996 August; 126(4): 339-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8878350&dopt=Abstract

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Perceived parental characteristics of patients with obsessive compulsive disorder, depression, and panic disorder. Author(s): Merkel WT, Pollard CA, Wiener RL, Staebler CR. Source: Child Psychiatry and Human Development. 1993 Fall; 24(1): 49-57. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8404245&dopt=Abstract

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Perceptual alternation in obsessive compulsive disorder--implications for a role of the cortico-striatal circuitry in mediating awareness. Author(s): Li CS, Chen MC, Yang YY, Chang HL, Liu CY, Shen S, Chen CY. Source: Behavioural Brain Research. 2000 June 15; 111(1-2): 61-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10840132&dopt=Abstract

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Personality disorder in obsessive compulsive disorder: a controlled study. Author(s): Crino RD, Andrews G. Source: Journal of Psychiatric Research. 1996 January-February; 30(1): 29-38. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8736464&dopt=Abstract

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Personality disorders do not influence the results of cognitive and behavior therapy for obsessive compulsive disorder. Author(s): Dreessen L, Hoekstra R, Arntz A. Source: Journal of Anxiety Disorders. 1997 September-October; 11(5): 503-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9407270&dopt=Abstract

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Personality disorders in obsessive compulsive disorder. Author(s): Baer L, Jenike MA. Source: The Psychiatric Clinics of North America. 1992 December; 15(4): 803-12. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1461797&dopt=Abstract

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PET imaging in obsessive compulsive disorder with and without depression. Author(s): Baxter LR Jr, Schwartz JM, Guze BH, Bergman K, Szuba MP. Source: The Journal of Clinical Psychiatry. 1990 April; 51 Suppl: 61-9; Discussion 70. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2182617&dopt=Abstract

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Pharmacologic therapy of obsessive compulsive disorder. Author(s): DeVeaugh-Geiss J. Source: Adv Pharmacol. 1994; 30: 35-52. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7833296&dopt=Abstract

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Pharmacotherapy of obsessive compulsive disorder. Author(s): Goodman WK, McDougle CJ, Price LH. Source: The Journal of Clinical Psychiatry. 1992 April; 53 Suppl: 29-37. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1532962&dopt=Abstract

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Pharmacotherapy of obsessive compulsive disorder--experience with fluoxetine. Author(s): Wood A, Tollefson GD, Birkett M. Source: International Clinical Psychopharmacology. 1993 Winter; 8(4): 301-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8277151&dopt=Abstract

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Pindolol augmentation in treatment-resistant obsessive compulsive disorder: a double-blind placebo controlled trial. Author(s): Dannon PN, Sasson Y, Hirschmann S, Iancu I, Grunhaus LJ, Zohar J. Source: European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology. 2000 May; 10(3): 165-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10793318&dopt=Abstract

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Positron emission tomography studies of cerebral glucose metabolism in obsessive compulsive disorder. Author(s): Baxter LR Jr. Source: The Journal of Clinical Psychiatry. 1994 October; 55 Suppl: 54-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7961533&dopt=Abstract

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Possible role of neuropeptides in obsessive compulsive disorder. Author(s): McDougle CJ, Barr LC, Goodman WK, Price LH. Source: Psychoneuroendocrinology. 1999 January; 24(1): 1-24. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10098217&dopt=Abstract

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Postpartum obsessive compulsive disorder: a case series. Author(s): Sichel DA, Cohen LS, Dimmock JA, Rosenbaum JF. Source: The Journal of Clinical Psychiatry. 1993 April; 54(4): 156-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8486594&dopt=Abstract

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Predictors of fluvoxamine response in contamination-related obsessive compulsive disorder: a PET symptom provocation study. Author(s): Rauch SL, Shin LM, Dougherty DD, Alpert NM, Fischman AJ, Jenike MA. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 2002 November; 27(5): 782-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12431852&dopt=Abstract

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Prevalence of obsessive compulsive disorder in first- and multi-episode male patients with schizophrenia-spectrum disorders. Author(s): Koen L, Oosthuizen PP, Niehaus DJ, Emsley RA, Muller JE, Stein DJ, Keyter N, Lochner C, Seedat S. Source: South African Medical Journal. Suid-Afrikaanse Tydskrif Vir Geneeskunde. 2003 July; 93(7): 517-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12939924&dopt=Abstract

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Progress toward analysis of D8/17 binding to B cells in children with obsessive compulsive disorder and/or chronic tic disorder. Author(s): Murphy TK, Benson N, Zaytoun A, Yang M, Braylan R, Ayoub E, Goodman WK. Source: Journal of Neuroimmunology. 2001 November 1; 120(1-2): 146-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11694329&dopt=Abstract

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Psychiatric disorders in first degree relatives of children and adolescents with obsessive compulsive disorder. Author(s): Lenane MC, Swedo SE, Leonard H, Pauls DL, Sceery W, Rapoport JL. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 1990 May; 29(3): 407-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2347838&dopt=Abstract

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Psychopharmacologic treatment of child and adolescent obsessive compulsive disorder. Author(s): Piacentini J, Jaffer M, Gitow A, Graae F, Davies SO, Del Bene D, Liebowitz M. Source: The Psychiatric Clinics of North America. 1992 March; 15(1): 87-107. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1549550&dopt=Abstract

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Quantitative EEG analysis in obsessive compulsive disorder. Author(s): Karadag F, Oguzhanoglu NK, Kurt T, Oguzhanoglu A, Atesci F, Ozdel O. Source: The International Journal of Neuroscience. 2003 June; 113(6): 833-47. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12775347&dopt=Abstract

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Rates of Obsessive Compulsive Disorder in first degree relatives of patients with trichotillomania: a research note. Author(s): Lenane MC, Swedo SE, Rapoport JL, Leonard H, Sceery W, Guroff JJ. Source: Journal of Child Psychology and Psychiatry, and Allied Disciplines. 1992 July; 33(5): 925-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1634595&dopt=Abstract

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Re: The influence of gonadal hormones on periodicity of obsessive compulsive disorder. Author(s): Warneke L. Source: Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. 1996 February; 41(1): 60-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8919426&dopt=Abstract

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Refractory obsessive compulsive disorder and ECT. Author(s): Maletzky B, McFarland B, Burt A. Source: Convuls Ther. 1994 March; 10(1): 34-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8055290&dopt=Abstract

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Response of obsessive compulsive disorder to carbamazepine in two patients with comorbid epilepsy. Author(s): Koopowitz LF, Berk M. Source: Annals of Clinical Psychiatry : Official Journal of the American Academy of Clinical Psychiatrists. 1997 September; 9(3): 171-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9339883&dopt=Abstract

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Responsibility attitudes and interpretations are characteristic of obsessive compulsive disorder. Author(s): Salkovskis PM, Wroe AL, Gledhill A, Morrison N, Forrester E, Richards C, Reynolds M, Thorpe S. Source: Behaviour Research and Therapy. 2000 April; 38(4): 347-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10761280&dopt=Abstract

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Revision of the Padua Inventory of obsessive compulsive disorder symptoms: distinctions between worry, obsessions, and compulsions. Author(s): Burns GL, Keortge SG, Formea GM, Sternberger LG. Source: Behaviour Research and Therapy. 1996 February; 34(2): 163-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8741724&dopt=Abstract

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Risperidone augmentation of serotonin reuptake inhibitor treatment of pediatric obsessive compulsive disorder. Author(s): Fitzgerald KD, Stewart CM, Tawile V, Rosenberg DR. Source: Journal of Child and Adolescent Psychopharmacology. 1999; 9(2): 115-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10461822&dopt=Abstract

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Selections from current literature: obsessive compulsive disorder. Author(s): Levine N. Source: Family Practice. 1997 June; 14(3): 258-61. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9201503&dopt=Abstract

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Selective processing of emotional information in obsessive compulsive disorder. Author(s): Lavy E, van Oppen P, van den Hout M. Source: Behaviour Research and Therapy. 1994 February; 32(2): 243-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8155063&dopt=Abstract

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Self-mutilation, anorexia, and dysmenorrhea in obsessive compulsive disorder. Author(s): Yaryura-Tobias JA, Neziroglu FA, Kaplan S. Source: The International Journal of Eating Disorders. 1995 January; 17(1): 33-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7894450&dopt=Abstract

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Self-treatment for obsessive compulsive disorder using a manual and a computerized telephone interview: a U.S.-U.K. study. Author(s): Greist JH, Marks IM, Baer L, Parkin JR, Manzo PA, Mantle JM, Wenzel KW, Spierings CJ, Kobak KA, Dottl SL, Bailey TM, Forman L. Source: Md Comput. 1998 May-June; 15(3): 149-57. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9617085&dopt=Abstract

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Serotonergic antidepressants and their efficacy in obsessive compulsive disorder. Author(s): Dominguez RA. Source: The Journal of Clinical Psychiatry. 1992 October; 53 Suppl: 56-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1429485&dopt=Abstract

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Serotonergic probes in obsessive compulsive disorder. Author(s): Zohar J, Kindler S. Source: International Clinical Psychopharmacology. 1992 June; 7 Suppl 1: 39-40. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1517556&dopt=Abstract

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Serotonin reuptake inhibitors are the treatment of choice in obsessive compulsive disorder. Author(s): Fineberg NA, Bullock T, Montgomery DB, Montgomery SA. Source: International Clinical Psychopharmacology. 1992 June; 7 Suppl 1: 43-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1517558&dopt=Abstract

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Sertraline in the treatment of obsessive compulsive disorder: two double-blind, placebo-controlled studies. Author(s): Chouinard G. Source: International Clinical Psychopharmacology. 1992 October; 7 Suppl 2: 37-41. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1484177&dopt=Abstract

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Serum cholesterol in patients with obsessive compulsive disorder during treatment with behavior therapy and SSRI or placebo. Author(s): Peter H, Tabrizian S, Hand I. Source: International Journal of Psychiatry in Medicine. 2000; 30(1): 27-39. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10900559&dopt=Abstract

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Sexual history and quality of current relationships in patients with obsessive compulsive disorder: a comparison with two other psychiatric samples. Author(s): Staebler CR, Pollard CA, Merkel WT. Source: Journal of Sex & Marital Therapy. 1993 Summer; 19(2): 147-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8336346&dopt=Abstract

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Sexuality in women with obsessive compulsive disorder. Author(s): Aksaray G, Yelken B, Kaptanoglu C, Oflu S, Ozaltin M. Source: Journal of Sex & Marital Therapy. 2001 May-June; 27(3): 273-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11354932&dopt=Abstract

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Single photon emission computerized tomography in obsessive compulsive disorder: a preliminary study. Author(s): Adams BL, Warneke LB, McEwan AJ, Fraser BA. Source: Journal of Psychiatry & Neuroscience : Jpn. 1993 May; 18(3): 109-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8499426&dopt=Abstract

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Six-year follow-up after exposure and clomipramine therapy for obsessive compulsive disorder. Author(s): O'Sullivan G, Noshirvani H, Marks I, Monteiro W, Lelliott P. Source: The Journal of Clinical Psychiatry. 1991 April; 52(4): 150-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2016246&dopt=Abstract

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Stability of subclinical obsessive compulsive disorder in college students. Author(s): Morris MR, Forbes S, Bradley MM, Goodman WK. Source: Depression and Anxiety. 2000; 11(4): 180-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10945139&dopt=Abstract

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Stimulus dimension shifts in patients with schizophrenia, with and without paranoid hallucinatory symptoms, or obsessive compulsive disorder: strategies, blocking and monoamine status. Author(s): Oades RD. Source: Behavioural Brain Research. 1997 October; 88(1): 115-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9401715&dopt=Abstract

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Strategic processing and episodic memory impairment in obsessive compulsive disorder. Author(s): Savage CR, Deckersbach T, Wilhelm S, Rauch SL, Baer L, Reid T, Jenike MA. Source: Neuropsychology. 2000 January; 14(1): 141-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10674806&dopt=Abstract

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Successful treatment of obsessive compulsive disorder with oxcarbazepine. A case report. Author(s): McMeekin H. Source: J S C Med Assoc. 2002 December; 98(8): 316-20. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12532658&dopt=Abstract

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Sumatriptan (5-HT1D receptor agonist) does not exacerbate symptoms in obsessive compulsive disorder. Author(s): Pian KL, Westenberg HG, van Megen HJ, den Boer JA. Source: Psychopharmacology. 1998 December; 140(3): 365-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9877016&dopt=Abstract

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Symptom relapse in bulimia nervosa and obsessive compulsive disorder after treatment with serotonin antagonists. Author(s): Hollander E, Mullen LS, Carrasco JL, DeCaria CM, Stein DJ. Source: The Journal of Clinical Psychiatry. 1992 January; 53(1): 28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1737737&dopt=Abstract

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The benefits of clomipramine-fluoxetine combination in obsessive compulsive disorder. Author(s): Browne M, Horn E, Jones TT. Source: Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. 1993 May; 38(4): 242-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8518974&dopt=Abstract

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The cAMP-dependent protein kinase substrate Rap1 in platelets from patients with obsessive compulsive disorder or schizophrenia. Author(s): Tardito D, Maina G, Tura GB, Bogetto F, Pioli R, Ravizza L, Racagni G, Perez J. Source: European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology. 2001 June; 11(3): 221-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11418282&dopt=Abstract

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The clomipramine challenge test in obsessive compulsive disorder. Author(s): Saiz J, Lopez-Ibor JJ Jr, Vinas R, Hernandez M. Source: International Clinical Psychopharmacology. 1992 June; 7 Suppl 1: 41-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1517557&dopt=Abstract

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The cross national epidemiology of obsessive compulsive disorder. The Cross National Collaborative Group. Author(s): Weissman MM, Bland RC, Canino GJ, Greenwald S, Hwu HG, Lee CK, Newman SC, Oakley-Browne MA, Rubio-Stipec M, Wickramaratne PJ, et al. Source: The Journal of Clinical Psychiatry. 1994 March; 55 Suppl: 5-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8077177&dopt=Abstract

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The epidemiology and clinical features of obsessive compulsive disorder. Author(s): Rasmussen SA, Eisen JL. Source: The Psychiatric Clinics of North America. 1992 December; 15(4): 743-58. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1461792&dopt=Abstract

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The epidemiology and differential diagnosis of obsessive compulsive disorder. Author(s): Rasmussen SA, Eisen JL. Source: The Journal of Clinical Psychiatry. 1994 October; 55 Suppl: 5-10; Discussion 11-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7961532&dopt=Abstract

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The epidemiology and differential diagnosis of obsessive compulsive disorder. Author(s): Rasmussen SA, Eisen JL. Source: The Journal of Clinical Psychiatry. 1992 April; 53 Suppl: 4-10. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1564054&dopt=Abstract

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The genetics of obsessive compulsive disorder and Gilles de la Tourette's syndrome. Author(s): Pauls DL. Source: The Psychiatric Clinics of North America. 1992 December; 15(4): 759-66. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1461793&dopt=Abstract

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The growth hormone response to baclofen in obsessive compulsive disorder: does the GABA-B receptor mediate obsessive anxiety? Author(s): Lucey JV, Butcher G, O'Flynn K, Clare AW, Dinan G. Source: Pharmacopsychiatry. 1994 January; 27(1): 23-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8159779&dopt=Abstract

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The influence of cultural factors on obsessive compulsive disorder: religious symptoms in a religious society. Author(s): Greenberg D, Witztum E. Source: The Israel Journal of Psychiatry and Related Sciences. 1994; 31(3): 211-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7868322&dopt=Abstract

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The place of obsessive compulsive disorder in the diagnostic hierarchy. Author(s): Montgomery SA. Source: International Clinical Psychopharmacology. 1992 June; 7 Suppl 1: 19-23. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1517551&dopt=Abstract

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The psychopharmacology of obsessive compulsive disorder. Implications for treatment and pathogenesis. Author(s): McDougle CJ, Goodman WK, Leckman JF, Price LH. Source: The Psychiatric Clinics of North America. 1993 December; 16(4): 749-66. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8309811&dopt=Abstract

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The role of central oxytocin in obsessive compulsive disorder and related normal behavior. Author(s): Leckman JF, Goodman WK, North WG, Chappell PB, Price LH, Pauls DL, Anderson GM, Riddle MA, McDougle CJ, Barr LC, et al. Source: Psychoneuroendocrinology. 1994; 19(8): 723-49. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7991761&dopt=Abstract

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The role of serotonin and dopamine in the pathophysiology of obsessive compulsive disorder. Author(s): Goodman WK, McDougle CJ, Price LH. Source: International Clinical Psychopharmacology. 1992 June; 7 Suppl 1: 35-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1517555&dopt=Abstract

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The serotonin hypothesis of obsessive compulsive disorder. Author(s): Barr LC, Goodman WK, Price LH. Source: International Clinical Psychopharmacology. 1993 November; 8 Suppl 2: 79-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8201248&dopt=Abstract

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The serotonin hypothesis of obsessive compulsive disorder: implications of pharmacologic challenge studies. Author(s): Barr LC, Goodman WK, Price LH, McDougle CJ, Charney DS. Source: The Journal of Clinical Psychiatry. 1992 April; 53 Suppl: 17-28. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1532961&dopt=Abstract

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The utilization of nonpatient samples in the study of obsessive compulsive disorder. Author(s): Burns GL, Formea GM, Keortge S, Sternberger LG. Source: Behaviour Research and Therapy. 1995 February; 33(2): 133-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7887872&dopt=Abstract

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The waking nightmare: an overview of obsessive compulsive disorder. Author(s): Rapoport JL. Source: The Journal of Clinical Psychiatry. 1990 November; 51 Suppl: 25-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2228991&dopt=Abstract

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Three case reports on the relationship between anorexia nervosa and obsessive compulsive disorder. Author(s): Fisher M, Fornari V, Waldbaum R, Gold R. Source: Int J Adolesc Med Health. 2002 October-December; 14(4): 329-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12613114&dopt=Abstract

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Tic-related vs. non-tic-related obsessive compulsive disorder. Author(s): Leckman JF, Grice DE, Barr LC, de Vries AL, Martin C, Cohen DJ, McDougle CJ, Goodman WK, Rasmussen SA. Source: Anxiety. 1994-95; 1(5): 208-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9160576&dopt=Abstract

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Tourette's syndrome and obsessive compulsive disorder. Clinical aspects. Author(s): Steingard R, Dillon-Stout D. Source: The Psychiatric Clinics of North America. 1992 December; 15(4): 849-60. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1461800&dopt=Abstract

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Toward a new nosology of obsessive compulsive disorder. Author(s): Tynes LL, White K, Steketee GS. Source: Comprehensive Psychiatry. 1990 September-October; 31(5): 465-80. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2225807&dopt=Abstract

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Treating obsessive compulsive disorder. Author(s): Veale D. Source: The Practitioner. 2002 March; 246(1632): 181, 184-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11901781&dopt=Abstract

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Treating obsessive compulsive disorder: a new role for infectious diseases physicians? Author(s): Hambridge J, Loewenthal M. Source: International Journal of Infectious Diseases : Ijid : Official Publication of the International Society for Infectious Diseases. 2003 June; 7(2): 152-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12839718&dopt=Abstract

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Treating the anxiety: therapeutic options in obsessive compulsive disorder. Author(s): Greist JH. Source: The Journal of Clinical Psychiatry. 1990 November; 51 Suppl: 29-34. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2146255&dopt=Abstract

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Treatment of obsessive compulsive disorder in the elderly: a review and case example. Author(s): Calamari JE, Faber SD, Hitsman BL, Poppe CJ. Source: Journal of Behavior Therapy and Experimental Psychiatry. 1994 June; 25(2): 95104. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7983229&dopt=Abstract

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Treatment of obsessive compulsive disorder: psychotherapies, drugs, and other somatic treatment. Author(s): Greist JH. Source: The Journal of Clinical Psychiatry. 1990 August; 51 Suppl: 44-50; Discussion 558. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2116405&dopt=Abstract

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Treatment of severe, drug resistant obsessive compulsive disorder with the 5HT1D agonist sumatriptan. Author(s): Stern L, Zohar J, Cohen R, Sasson Y. Source: European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology. 1998 December; 8(4): 325-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9928925&dopt=Abstract

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Treatment outcome of obsessive compulsive disorder with comorbid social phobia. Author(s): Carrasco JL, Hollander E, Schneier FR, Liebowitz MR. Source: The Journal of Clinical Psychiatry. 1992 November; 53(11): 387-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1459968&dopt=Abstract

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Update of the serotonergic hypothesis of obsessive compulsive disorder. Author(s): Zohar J, Kindler S. Source: Clinical Neuropharmacology. 1992; 15 Suppl 1 Pt A: 257A-258A. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1386779&dopt=Abstract

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Visuospatial priming and stroop performance in patients with obsessive compulsive disorder. Author(s): Hartston HJ, Swerdlow NR. Source: Neuropsychology. 1999 July; 13(3): 447-57. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10447305&dopt=Abstract

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What is obsessive compulsive disorder? The clinical syndrome and its boundaries. Author(s): Freeman CP. Source: International Clinical Psychopharmacology. 1992 June; 7 Suppl 1: 11-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1517550&dopt=Abstract

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What predicts improvement and compliance during the behavioral treatment of obsessive compulsive disorder? Author(s): Buchanan AW, Meng KS, Marks IM. Source: Anxiety. 1996; 2(1): 22-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9160595&dopt=Abstract

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Working with children with obsessive compulsive disorder. Author(s): Nicoletto-Syrett L. Source: Journal of Psychosocial Nursing and Mental Health Services. 2002 June; 40(6): 36-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12073279&dopt=Abstract

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Zolmitriptan (a 5-HT1B/1D receptor agonist with central action) does not increase symptoms in obsessive compulsive disorder. Author(s): Boshuisen ML, den Boer JA. Source: Psychopharmacology. 2000 September; 152(1): 74-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11041318&dopt=Abstract

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CHAPTER 2. NUTRITION AND OBSESSIVE COMPULSIVE DISORDER Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and obsessive compulsive disorder.

Finding Nutrition Studies on Obsessive Compulsive Disorder The National Institutes of Health’s Office of Dietary Supplements (ODS) offers a searchable bibliographic database called the IBIDS (International Bibliographic Information on Dietary Supplements; National Institutes of Health, Building 31, Room 1B29, 31 Center Drive, MSC 2086, Bethesda, Maryland 20892-2086, Tel: 301-435-2920, Fax: 301-480-1845, E-mail: [email protected]). The IBIDS contains over 460,000 scientific citations and summaries about dietary supplements and nutrition as well as references to published international, scientific literature on dietary supplements such as vitamins, minerals, and botanicals.7 The IBIDS includes references and citations to both human and animal research studies. As a service of the ODS, access to the IBIDS database is available free of charge at the following Web address: http://ods.od.nih.gov/databases/ibids.html. After entering the search area, you have three choices: (1) IBIDS Consumer Database, (2) Full IBIDS Database, or (3) Peer Reviewed Citations Only. Now that you have selected a database, click on the “Advanced” tab. An advanced search allows you to retrieve up to 100 fully explained references in a comprehensive format. Type “obsessive compulsive disorder” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.

7 Adapted from http://ods.od.nih.gov. IBIDS is produced by the Office of Dietary Supplements (ODS) at the National Institutes of Health to assist the public, healthcare providers, educators, and researchers in locating credible, scientific information on dietary supplements. IBIDS was developed and will be maintained through an interagency partnership with the Food and Nutrition Information Center of the National Agricultural Library, U.S. Department of Agriculture.

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The following information is typical of that found when using the “Full IBIDS Database” to search for “obsessive compulsive disorder” (or a synonym): •

Aberrant snacking patterns and eating disorders in patients with obsessive compulsive disorder. Author(s): Clinical Research Center, Massachusetts Institute of Technology, Cambridge. Source: O'Rourke, D A Wurtman, J J Wurtman, R J Tsay, R Gleason, R Baer, L Jenike, M A J-Clin-Psychiatry. 1994 October; 55(10): 445-7 0160-6689

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Are the eating disorders related to obsessive compulsive disorder? Author(s): University of Pittsburgh School of Medicine, PA. Source: Hsu, L K Kaye, W Weltzin, T Int-J-Eat-Disord. 1993 November; 14(3): 305-18 0276-3478

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Biological approaches to treatment-resistant obsessive compulsive disorder. Author(s): Yale University School of Medicine, Department of Psychiatry, New Haven, CT 06519. Source: Goodman, W K McDougle, C J Barr, L C Aronson, S C Price, L H J-ClinPsychiatry. 1993 June; 54 Suppl16-26 0160-6689

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Clomipramine. An overview of its pharmacological properties and a review of its therapeutic use in obsessive compulsive disorder and panic disorder. Author(s): ADIS Drug Information Services, Auckland, New Zealand. Source: McTavish, D Benfield, P Drugs. 1990 January; 39(1): 136-53 0012-6667

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Dopamine function in obsessive compulsive disorder: cortisol response to acute apomorphine stimulation. Author(s): Dipartimento di Scienze Neuropsichiche, Centro di Psioconeuroendocrinologia, Istituto Scientifico Ospedale S. Raffaele, Milan, Italy. Source: Brambilla, F Perna, G Bussi, R Bellodi, L Psychoneuroendocrinology. 2000 April; 25(3): 301-10 0306-4530

•

Factor structure and predictive validity of the Obsessive Compulsive Drinking Scale. Author(s): Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Alcohol Research Center, Charleston 29425, USA. [email protected] Source: Roberts, J S Anton, R F Latham, P K Moak, D H Alcohol-Clin-Exp-Res. 1999 September; 23(9): 1484-91 0145-6008

•

Obsessive compulsive comorbidity in the dieting disorders. Author(s): Eating Disorders Unit, Northside Clinic, Sydney, Australia. Source: Thornton, C Russell, J Int-J-Eat-Disord. 1997 January; 21(1): 83-7 0276-3478

•

Oxytocin in obsessive compulsive disorder. Author(s): Department of Biological Psychiatry, Academical Hospital Utrecht, The Netherlands. Source: den Boer, J A Westenberg, H G Peptides. 1992 Nov-December; 13(6): 1083-5 0196-9781

•

Pentagastrin has panic-inducing properties in obsessive compulsive disorder. Author(s): Department of Psychiatry, Academic Hospital Utrecht, The Netherlands. Source: de Leeuw, A S Den Boer, J A Slaap, B R Westenberg, H G Psychopharmacology(Berl). 1996 August; 126(4): 339-44 0033-3158

•

The influence of cultural factors on obsessive compulsive disorder: religious symptoms in a religious society. Author(s): Jerusalem Mental Health Center, Israel. Source: Greenberg, D Witztum, E Isr-J-Psychiatry-Relat-Sci. 1994; 31(3): 211-20 0333-7308

Nutrition

•

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Vitamin B12 and folic acid serum levels in obsessive compulsive disorder. Author(s): Geha Psychiatric Hospital, Beilinson Medical Center, Sackler School of Medicine, Tel Aviv University, Israel. Source: Hermesh, H Weizman, A Shahar, A Munitz, H Acta-Psychiatr-Scand. 1988 July; 78(1): 8-10 0001-690X

Federal Resources on Nutrition In addition to the IBIDS, the United States Department of Health and Human Services (HHS) and the United States Department of Agriculture (USDA) provide many sources of information on general nutrition and health. Recommended resources include: •

healthfinder®, HHS’s gateway to health information, including diet and nutrition: http://www.healthfinder.gov/scripts/SearchContext.asp?topic=238&page=0

•

The United States Department of Agriculture’s Web site dedicated to nutrition information: www.nutrition.gov

•

The Food and Drug Administration’s Web site for federal food safety information: www.foodsafety.gov

•

The National Action Plan on Overweight and Obesity sponsored by the United States Surgeon General: http://www.surgeongeneral.gov/topics/obesity/

•

The Center for Food Safety and Applied Nutrition has an Internet site sponsored by the Food and Drug Administration and the Department of Health and Human Services: http://vm.cfsan.fda.gov/

•

Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/

•

Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/

•

Food and Nutrition Service sponsored by the United States Department of Agriculture: http://www.fns.usda.gov/fns/

Additional Web Resources A number of additional Web sites offer encyclopedic information covering food and nutrition. The following is a representative sample: •

AOL: http://search.aol.com/cat.adp?id=174&layer=&from=subcats

•

Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html

•

Google: http://directory.google.com/Top/Health/Nutrition/

•

Healthnotes: http://www.healthnotes.com/

•

Open Directory Project: http://dmoz.org/Health/Nutrition/

•

Yahoo.com: http://dir.yahoo.com/Health/Nutrition/

•

WebMDHealth: http://my.webmd.com/nutrition

•

WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html

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CHAPTER 3. ALTERNATIVE MEDICINE AND OBSESSIVE COMPULSIVE DISORDER Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to obsessive compulsive disorder. At the conclusion of this chapter, we will provide additional sources.

National Center for Complementary and Alternative Medicine The National Center for Complementary and Alternative Medicine (NCCAM) of the National Institutes of Health (http://nccam.nih.gov/) has created a link to the National Library of Medicine’s databases to facilitate research for articles that specifically relate to obsessive compulsive disorder and complementary medicine. To search the database, go to the following Web site: http://www.nlm.nih.gov/nccam/camonpubmed.html. Select “CAM on PubMed.” Enter “obsessive compulsive disorder” (or synonyms) into the search box. Click “Go.” The following references provide information on particular aspects of complementary and alternative medicine that are related to obsessive compulsive disorder: •

“Change the mind and you change the brain”: effects of cognitive-behavioral therapy on the neural correlates of spider phobia. Author(s): Paquette V, Levesque J, Mensour B, Leroux JM, Beaudoin G, Bourgouin P, Beauregard M. Source: Neuroimage. 2003 February; 18(2): 401-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12595193&dopt=Abstract

•

“Dude, you don't have Tourette's:” Tourette's syndrome, beyond the tics. Author(s): Schapiro NA. Source: Pediatric Nursing. 2002 May-June; 28(3): 243-6, 249-53. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12087644&dopt=Abstract

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A fluoxetine-induced frontal lobe syndrome in an obsessive compulsive patient. Author(s): Hoehn-Saric R, Harris GJ, Pearlson GD, Cox CS, Machlin SR, Camargo EE. Source: The Journal of Clinical Psychiatry. 1991 March; 52(3): 131-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2005077&dopt=Abstract

•

Cerebral metabolic correlates as potential predictors of response to anterior cingulotomy for obsessive compulsive disorder. Author(s): Rauch SL, Dougherty DD, Cosgrove GR, Cassem EH, Alpert NM, Price BH, Nierenberg AA, Mayberg HS, Baer L, Jenike MA, Fischman AJ. Source: Biological Psychiatry. 2001 November 1; 50(9): 659-67. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11704072&dopt=Abstract

•

Clinical case report: efficacy of yogic techniques in the treatment of obsessive compulsive disorders. Author(s): Shannahoff-Khalsa DS, Beckett LR. Source: The International Journal of Neuroscience. 1996 March; 85(1-2): 1-17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8727678&dopt=Abstract

•

FDG-PET predictors of response to behavioral therapy and pharmacotherapy in obsessive compulsive disorder. Author(s): Brody AL, Saxena S, Schwartz JM, Stoessel PW, Maidment K, Phelps ME, Baxter LR Jr. Source: Psychiatry Research. 1998 November 9; 84(1): 1-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9870412&dopt=Abstract

•

Neurobiology of obsessive compulsive disorder. Author(s): Wright M, Hewlett WA. Source: Compr Ther. 1994; 20(2): 95-100. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7911407&dopt=Abstract

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Neurobiology of obsessive compulsive disorder. Author(s): Insel TR, Winslow JT. Source: The Psychiatric Clinics of North America. 1992 December; 15(4): 813-24. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1461798&dopt=Abstract

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Obsessive compulsive disorder in ultra-orthodox Jewish patients: a comparison of religious and non-religious symptoms. Author(s): Greenberg D, Shefler G. Source: Psychology and Psychotherapy. 2002 June; 75(Pt 2): 123-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12396759&dopt=Abstract

•

Obsessive compulsive disorder manifesting as demonic attack. Author(s): Lacy TJ, Khatain KG.

Alternative Medicine 97

Source: The Journal of Clinical Psychiatry. 1993 October; 54(10): 398. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8262885&dopt=Abstract •

Obsessive compulsive disorder. Author(s): Clark L. Source: Can Fam Physician. 1999 August; 45: 1939-40. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10463095&dopt=Abstract

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Obsessive compulsive disorder: is there an association with childhood streptococcal infections and altered immune function? Author(s): Murphy TK, Petitto JM, Voeller KK, Goodman WK. Source: Semin Clin Neuropsychiatry. 2001 October; 6(4): 266-76. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11607922&dopt=Abstract

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Positron emission tomography studies of cerebral glucose metabolism in obsessive compulsive disorder. Author(s): Baxter LR Jr. Source: The Journal of Clinical Psychiatry. 1994 October; 55 Suppl: 54-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7961533&dopt=Abstract

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Predictors of fluvoxamine response in contamination-related obsessive compulsive disorder: a PET symptom provocation study. Author(s): Rauch SL, Shin LM, Dougherty DD, Alpert NM, Fischman AJ, Jenike MA. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 2002 November; 27(5): 782-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12431852&dopt=Abstract

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Regional cerebral blood flow changes in patients with intractable obsessive compulsive disorders treated by limbic leukotomy. Author(s): Kim MC, Lee TK, Son BC, Choi CR, Lee C. Source: Stereotactic and Functional Neurosurgery. 2001; 76(3-4): 249-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12378105&dopt=Abstract

•

The influence of cultural factors on obsessive compulsive disorder: religious symptoms in a religious society. Author(s): Greenberg D, Witztum E. Source: The Israel Journal of Psychiatry and Related Sciences. 1994; 31(3): 211-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7868322&dopt=Abstract

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Additional Web Resources A number of additional Web sites offer encyclopedic information covering CAM and related topics. The following is a representative sample: •

Alternative Medicine Foundation, Inc.: http://www.herbmed.org/

•

AOL: http://search.aol.com/cat.adp?id=169&layer=&from=subcats

•

Chinese Medicine: http://www.newcenturynutrition.com/

•

drkoop.com: http://www.drkoop.com/InteractiveMedicine/IndexC.html

•

Family Village: http://www.familyvillage.wisc.edu/med_altn.htm

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Google: http://directory.google.com/Top/Health/Alternative/

•

Healthnotes: http://www.healthnotes.com/

•

MedWebPlus: http://medwebplus.com/subject/Alternative_and_Complementary_Medicine

•

Open Directory Project: http://dmoz.org/Health/Alternative/

•

HealthGate: http://www.tnp.com/

•

WebMDHealth: http://my.webmd.com/drugs_and_herbs

•

WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html

•

Yahoo.com: http://dir.yahoo.com/Health/Alternative_Medicine/

General References A good place to find general background information on CAM is the National Library of Medicine. It has prepared within the MEDLINEplus system an information topic page dedicated to complementary and alternative medicine. To access this page, go to the MEDLINEplus site at http://www.nlm.nih.gov/medlineplus/alternativemedicine.html. This Web site provides a general overview of various topics and can lead to a number of general sources.

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CHAPTER 4. DISSERTATIONS ON OBSESSIVE COMPULSIVE DISORDER Overview In this chapter, we will give you a bibliography on recent dissertations relating to obsessive compulsive disorder. We will also provide you with information on how to use the Internet to stay current on dissertations. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical dissertations that use the generic term “obsessive compulsive disorder” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on obsessive compulsive disorder, we have not necessarily excluded non-medical dissertations in this bibliography.

Dissertations on Obsessive Compulsive Disorder ProQuest Digital Dissertations, the largest archive of academic dissertations available, is located at the following Web address: http://wwwlib.umi.com/dissertations. From this archive, we have compiled the following list covering dissertations devoted to obsessive compulsive disorder. You will see that the information provided includes the dissertation’s title, its author, and the institution with which the author is associated. The following covers recent dissertations found when using this search procedure: •

Functioning in Adults with Obsessive Compulsive Disorder and Family Responses: a Transactional Perspective by Van Noppen, Barbara Livingston; PhD from Simmons College School of Social Work, 2003, 380 pages http://wwwlib.umi.com/dissertations/fullcit/3081998

•

Impulsivity, Compulsivity, and Obsessive Compulsive Disorder among Various Sex Offender Groups by Westergren, Amy J.; PhD from Auburn University, 2002, 208 pages http://wwwlib.umi.com/dissertations/fullcit/3057175

•

Personality in Obsessive Compulsive Disorder and Other Proposed Obsessive Compulsive Spectrum Disorders Using the Five-factor Model by Leong, Yung-mei; PhD from The Catholic University of America, 2003, 233 pages http://wwwlib.umi.com/dissertations/fullcit/3084425

100 Obsessive Compulsive Disorder

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Suppression of Intrusive Thoughts in Obsessive Compulsive Disorder and a Nonclinical Sample by Lowery, Natasha Gwartney; PhD from The University of Tulsa, 2002, 165 pages http://wwwlib.umi.com/dissertations/fullcit/3069303

•

The Effectiveness of Cognitive Behavior Therapy in a Partial Hospital Setting with Pediatric Obsessive Compulsive Patients by Cannon, Nancy Anne; PsyD from Adler School of Professional Psychology, 2003, 79 pages http://wwwlib.umi.com/dissertations/fullcit/3093272

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The Game of Life: a Naturalistic Study of Communication Patterns of a Young Boy with Obsessive Compulsive Disorder, His Family and a Friend by Burns, Susan C.; EDD from University of Cincinnati, 1999, 235 pages http://wwwlib.umi.com/dissertations/fullcit/9960868

•

The Relationship between the Presence of Obsessive Compulsive Disorder and Social Competence in Adolescents by Adams, Gail Barbara, EDD from Northern Illinois University, 1994, 194 pages http://wwwlib.umi.com/dissertations/fullcit/9510142

Keeping Current Ask the medical librarian at your library if it has full and unlimited access to the ProQuest Digital Dissertations database. From the library, you should be able to do more complete searches via http://wwwlib.umi.com/dissertations.

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CHAPTER 5. CLINICAL COMPULSIVE DISORDER

TRIALS

AND

OBSESSIVE

Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning obsessive compulsive disorder.

Recent Trials on Obsessive Compulsive Disorder The following is a list of recent trials dedicated to obsessive compulsive disorder.8 Further information on a trial is available at the Web site indicated. •

Cognitive Behavioral Therapy Plus Drug Treatment for Obsessive Compulsive Disorder Condition(s): Obsessive-Compulsive Disorder Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: The purpose of this study is to compare the effectiveness of 2 cognitive behavioral therapies (CBTs) in treating obsessive compulsive disorder (OCD) in patients who are taking medication but still have residual symptoms. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00045903

•

Cortical Excitability in Obsessive-Compulsive and Related Disorders Condition(s): Obsessive Compulsive Disorder; Healthy Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH)

8

These are listed at www.ClinicalTrials.gov.

102 Obsessive Compulsive Disorder

Purpose - Excerpt: This study will use transcranial magnetic stimulation (TMS) to study the function of the cerebral cortex (outer layer of the brain) in people with obsessive compulsive disorder (OCD) and related disorders. A non-invasive procedure, TMS activates areas of the brain with magnetic pulses that travel through the scalp and head and cause small electrical currents in the brain. People 18 years of age and older with OCD and disorders that may be related-tic disorders, such as Tourette's syndrome, focal dystonia (localized muscle cramps), body dysmorphic disorder (hypersensitivity to changes in appearance), eating disorders, such as anorexia nervosa, trichotillomania (compulsive hair-pulling)-may be eligible for this study. Healthy normal volunteers will also be enrolled. Candidates will be screened by telephone interview. Participants will undergo TMS. For this procedure, an insulated wire coil is placed on the subject's head. A brief electrical current passes through the coil, creating a magnetic pulse that travels through the scalp and skull and causes small electrical currents in the outer part of the brain. The stimulation may cause muscle, hand or arm twitching, or may affect movement or reflexes. During the stimulation, the subject may be asked to tense certain muscles slightly or perform other simple actions. The electrical activity of muscles during stimulation is recorded with a computer or other recording device, using electrodes attached to the skin with tape. Subjects will receive fewer than 500 magnetic pulses, and the study will take less than 3 hours. Participants may repeat the procedure on several occasions, if they agree. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00029068 •

Deep Brain Stimulation for Treatment-Resistant Obsessive Compulsive Disorder Condition(s): Obsessive-Compulsive Disorder Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: The purpose of this study is to evaluate the use of Deep Brain Stimulation (DBS) to reduce symptom severity and enhance the quality of life for patients with treatment-resistant obsessive compulsive disorder (OCD). Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00057603

•

Developmental Phenomenology of Obsessive Compulsive Disorder and Tourette Syndrome in Children and Adolescents Condition(s): Tourette Syndrome; Obsessive Compulsive Disorder Study Status: This study is currently recruiting patients. Sponsor(s): National Center for Research Resources (NCRR); Yale University Purpose - Excerpt: Objectives: I. Characterize the natural history, associated features, and severity of symptoms of obsessive compulsive disorder and Tourette syndrome in children and adolescents. II. Identify factors that influence the clinical course and prognosis of these patients. Study Type: Observational

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Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004324 •

Evaluation and Follow-up of Individuals with Obsessive-Compulsive Disorder and Related Conditions Condition(s): Anorexia Nervosa; Obsessive Compulsive Disorder; Tourette Syndrome; Trichotillomania Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: The purpose of this study is to better understand the long-term progress of people with obsessive-compulsive disorder (OCD) and related conditions such as anorexia nervosa, Tourette syndrome, and trichotillomania. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004550

•

Family Based Treatment of Early Childhood Obsessive Compulsive Disorder (OCD) Condition(s): Obsessive Compulsive Disorder (OCD) Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: The purpose of this study is to evaluate a treatment program for young children with Obsessive Compulsive Disorder (OCD) and their families. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00055068

•

Genetics of Obsessive-Compulsive Disorder Condition(s): Obsessive Compulsive Disorder Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: The purpose of this study is to identify genes that affect susceptibility to obsessive-compulsive disorder (OCD). By identifying genes that increase or decrease the risk of OCD, researchers can better understand how the condition develops and ultimately improve treatment for people with OCD. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001548

•

Phase II Randomized Study of Intravenous Versus Oral Clomipramine in Patients With Obsessive Compulsive Disorder Condition(s): Obsessive-Compulsive Disorder

104 Obsessive Compulsive Disorder

Study Status: This study is currently recruiting patients. Sponsor(s): National Center for Research Resources (NCRR); Stanford University Purpose - Excerpt: Objectives: I. Evaluate the efficacy of intravenous versus oral pulse loading of clomipramine (CMI) followed by a 12-week course of maintenance therapy in patients with obsessive compulsive disorder. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004310 •

Preventive Measures for Childhood-Onset Obsessive-Compulsive Disorder and Tic Disorders (PANDAS Subgroup) Condition(s): Chorea; Mental Disorder Diagnosed in Childhood; Obsessive Compulsive Disorder; Streptococcal Infection; Tic Disorder Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: The purpose of this study is to determine whether penicillin prevents the symptoms of Obsessive-compulsive Disorder (OCD) and tic disorders from recurring in children with Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus (PANDAS). Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001359

•

St. John's Wort vs. Placebo in Obsessive-Compulsive Disorder. Condition(s): Obsessive Compulsive Disorder Study Status: This study is currently recruiting patients. Sponsor(s): National Center for Complementary and Alternative Medicine (NCCAM) Purpose - Excerpt: The purpose of this study is to determine the effectiveness of St. John's Wort as compared to placebo (an inactive substance) in the treatment of outpatients with obsessive compulsive disorder. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00035438

•

Study of the Neurobiology of Tourette Syndrome and Related Disorders Condition(s): Tourette Syndrome; Obsessive Compulsive Disorder Study Status: This study is currently recruiting patients. Sponsor(s): National Center for Research Resources (NCRR); Yale University

Clinical Trials 105

Purpose - Excerpt: Objectives: I. Investigate the pathobiology of Tourette syndrome and related disorders by measuring various compounds of interest in cerebrospinal fluid, plasma, and urine of patients with Tourette syndrome, obsessive compulsive disorder, and/or chronic tics. II. Determine the pattern of familial aggregation of Tourette syndrome and obsessive compulsive disorder by systematic assessment of all firstdegree family members of patients selected for cerebrospinal fluid studies. III. Establish the neurochemical and neuropeptide profile associated with the range of expression of the putative Tourette gene expression in adult and adolescent patients. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004325 •

Amoxicillin for the Treatment of Pediatric Autoimmune Disorders Associated with Streptococcal Infections Condition(s): Autoimmune Disease; Mental Disorder; Obsessive Compulsive Disorder; Streptococcal Infection; Tic Disorder Study Status: This study is completed. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: Bacteria carry substances on their surface called antigens. When antigens come into contact with the right kinds of cells in the body an immune reaction is caused. This reaction is often the symptoms of sickness that a patient feels. In order for the body to fight off the attack of antigens, it creates substances called antibodies. Antibodies counter the action of antigens and make the bacteria harmless. However, the immune system must learn how to make the right antibodies for the right antigens. Sometimes the body creates antibodies that confuse normal tissues as foreign and attack them. This is called an autoimmune reaction and sometimes occurs when the body is exposed to certain bacteria. One bacteria known for causing autoimmune reactions is Group A beta-hemolytic Streptococcus (GABHS). This bacteria often causes throat infections commonly known as "strep throat". Some researchers believe that the autoimmune reaction associated with strep throat infections may cause neuropsychiatric disorders, like obsessive-compulsive disorder and/or tic disorder in children. As a result, each time a child with one of these disorders experiences an infection with GABHS his/her symptoms can reoccur or worsen. Researchers believe that by giving patients a certain antibiotic, they can prevent GABHS infection and thus prevent the return of symptoms. This study is designed to test the effectiveness of the antibiotc Amoxicillin for the treatment of Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections (PANDAS). Patients will receive Amoxicillin for six weeks and placebos "inactive sugar pills" for six weeks in order to see if the medication is truly working. Effectiveness of the treatment will be based on the presence or absence of symptoms. If at the end of the study Amoxicillin is proven to be effective treatment for PANDAS patients may be offered the opportunity to continue taking the medication for an additional six months. Phase(s): Phase IV Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001658

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I-123 Brain Studies of Serotonin Metabolism in Psychiatric Patients and Normal Volunteers Condition(s): Healthy; Mental Schizophrenia; Tourette Syndrome

Disorder;

Obsessive

Compulsive

Disorder;

Study Status: This study is completed. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: Abnormalities in the re-uptake of dopamine and serotonin have been described in various neuropsychiatric disorders and substance abuse. [I-123] Beta-CIT is a recently developed radioligand for SPECT imaging of dopamine and serotonin transporters. [I-123]Beta-CIT SPECT has been used at the SPECT-lab of the Clinical Brain Disorders Branch in over fifty subjects without adverse events. Due to the trace concentrations used, a pharmacological effect of Beta-CIT is unlikely and has not been observed. The purpose of this study is to use Beta-CIT and SPECT to study the expression of dopamine and serotonin transporters in vivo in normal controls and various patient populations to address hypothesized abnormalities of the transporters in different disorders and to understand the effects of genetic variations in the genes of these transporters on their in vivo expression. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001771

Keeping Current on Clinical Trials The U.S. National Institutes of Health, through the National Library of Medicine, has developed ClinicalTrials.gov to provide current information about clinical research across the broadest number of diseases and conditions. The site was launched in February 2000 and currently contains approximately 5,700 clinical studies in over 59,000 locations worldwide, with most studies being conducted in the United States. ClinicalTrials.gov receives about 2 million hits per month and hosts approximately 5,400 visitors daily. To access this database, simply go to the Web site at http://www.clinicaltrials.gov/ and search by “obsessive compulsive disorder” (or synonyms). While ClinicalTrials.gov is the most comprehensive listing of NIH-supported clinical trials available, not all trials are in the database. The database is updated regularly, so clinical trials are continually being added. The following is a list of specialty databases affiliated with the National Institutes of Health that offer additional information on trials: •

For clinical studies at the Warren Grant Magnuson Clinical Center located in Bethesda, Maryland, visit their Web site: http://clinicalstudies.info.nih.gov/

•

For clinical studies conducted at the Bayview Campus in Baltimore, Maryland, visit their Web site: http://www.jhbmc.jhu.edu/studies/index.html

•

For cancer trials, visit the National Cancer Institute: http://cancertrials.nci.nih.gov/

•

For eye-related trials, visit and search the Web page of the National Eye Institute: http://www.nei.nih.gov/neitrials/index.htm

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•

For heart, lung and blood trials, visit the Web page of the National Heart, Lung and Blood Institute: http://www.nhlbi.nih.gov/studies/index.htm

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For trials on aging, visit and search the Web site of the National Institute on Aging: http://www.grc.nia.nih.gov/studies/index.htm

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For rare diseases, visit and search the Web site sponsored by the Office of Rare Diseases: http://ord.aspensys.com/asp/resources/rsch_trials.asp

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For alcoholism, visit the National Institute on Alcohol Abuse and Alcoholism: http://www.niaaa.nih.gov/intramural/Web_dicbr_hp/particip.htm

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For trials on infectious, immune, and allergic diseases, visit the site of the National Institute of Allergy and Infectious Diseases: http://www.niaid.nih.gov/clintrials/

•

For trials on arthritis, musculoskeletal and skin diseases, visit newly revised site of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health: http://www.niams.nih.gov/hi/studies/index.htm

•

For hearing-related trials, visit the National Institute on Deafness and Other Communication Disorders: http://www.nidcd.nih.gov/health/clinical/index.htm

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For trials on diseases of the digestive system and kidneys, and diabetes, visit the National Institute of Diabetes and Digestive and Kidney Diseases: http://www.niddk.nih.gov/patient/patient.htm

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For drug abuse trials, visit and search the Web site sponsored by the National Institute on Drug Abuse: http://www.nida.nih.gov/CTN/Index.htm

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For trials on mental disorders, visit and search the Web site of the National Institute of Mental Health: http://www.nimh.nih.gov/studies/index.cfm

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For trials on neurological disorders and stroke, visit and search the Web site sponsored by the National Institute of Neurological Disorders and Stroke of the NIH: http://www.ninds.nih.gov/funding/funding_opportunities.htm#Clinical_Trials

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CHAPTER 6. PATENTS ON OBSESSIVE COMPULSIVE DISORDER Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.9 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “obsessive compulsive disorder” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on obsessive compulsive disorder, we have not necessarily excluded non-medical patents in this bibliography.

Patents on Obsessive Compulsive Disorder By performing a patent search focusing on obsessive compulsive disorder, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent 9Adapted from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.

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descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We will tell you how to obtain this information later in the chapter. The following is an example of the type of information that you can expect to obtain from a patent search on obsessive compulsive disorder: •

Biodegradable polymer encapsulated pharmaceutical compositions and method for preparing the same Inventor(s): Comiskey; Stephen J. (Doylestown, PA), Hanley; Stephen J. (Lebanon, NJ), Kohn; Rachel S. (Springfield, NJ) Assignee(s): Aventis Pharmaceuticals, Inc. (Bridgewater, NJ) Patent Number: 6,455,526 Date filed: December 7, 1999 Abstract: A new class of biodegradable pharmaceutical compositions useful as sustained release medicamentous compositions, including methods of making and methods of using these compositions, are described and claimed. The method of making these compositions include the steps of: a) dry mixing of a pharmaceutically active molecule with a biodegradable polymer; b) melt extruding the mixture to form a solid solution of the active molecule in the polymer; and c) pulverizing the solid solution to form microparticles such that they can be formed into injectable formulations. Preferred embodiments include pharmaceutical compositions of polylactide-co-glycolide and (+).alpha.-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4-piperidine methanol (active ingredient) and a method for its formation. These compositions release the active ingredient at a steady rate over a period of days to weeks. The active ingredient antagonizes the effects of serotonin at the 5HT.sub.2A receptor and are useful in treating various conditions such as, for example, psychoses including schizophrenia, obsessive compulsive disorder, sleep disorder, depression, anorexia, anxiety, drug addiction and bipolar disorders. Excerpt(s): This invention relates to methods for the production of sustained release compositions containing a biodegradable polymer and a pharmaceutically active molecule, which are useful in the treatment of a variety of diseases, including certain psychoses such as, for example, schizophrenia, obsessive compulsive disorder, anxiety, and bipolar disorders. More specifically, the present invention relates to sustained release compositions of a biodegradable polyester and a pharmaceutically active molecule capable of exerting serotonin receptor antagonist activity at the 5HT.sub.2 receptor, method of making the same, and method of treating patients in need of such compositions. It has long been appreciated that the continuous release of certain drugs over an extended period following a single administration could have significant practical advantages in clinical practice. It is also well recognized in the art that delivering a drug to its therapeutic site of action, such as, for example, the central nervous system (CNS) can be a very difficult task because of the numerous chemical and physical barriers which must be overcome in order for such delivery to be successful. A particularly difficult problem is in long term administration of a drug to patients suffering from CNS related diseases. This is particularly true for patients suffering from various CNS related diseases, such as schizophrenia, obsessive compulsive disorders, sleep disorders, depression, anxiety, anorexia and drug addiction. In addition, there is a need to maintain a steady drug level in patients suffering with these diseases so as to provide an improved efficacy in treatment with lower peak drug concentrations. As a result, many methods have been developed to deliver drugs to the CNS effectively. One such method involves preparation of sustained release formulations. The sustained

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release formulations may however be of various different types. For example, a drug may be chemically modified into a form called a prodrug, that is capable of transforming into its active form slowly, either before or after crossing the blood-brain barrier. An example of such a prodrug delivery system consists of the neurotransmitter dopamine attached to a molecular mask derived from the fat-soluble vitamin niacin. The modified dopamine is taken up into the brain where it is then slowly stripped from its prodrug mask to yield free dopamine. Web site: http://www.delphion.com/details?pn=US06455526__ •

Compositions containing sertraline and a 5-HT.sub.1D receptor agonist or antagonist Inventor(s): Chenard; Bertrand L. (New York, NY), Howard; Harry R. (New York, NY), Macor; John E. (New York, NY), Schulz; David W. (New York, NY), Sprouse; Jeffrey S. (New York, NY) Assignee(s): Pfizer Inc. (New York, NY) Patent Number: 5,597,826 Date filed: September 14, 1994 Abstract: The present invention relates to novel compositions containing the serotonin selective re-uptake inhibitor (SSRI), preferably (1S-cis)-4-(3,4-dichlorophenyl)-1,2,3,4tetrahydro-N-methyl-1-naphthalenam ine, and an agonist or antagonist of the serotonin 1 (5-HT.sub.1) receptor and to the use of such compositions for treating or preventing a condition selected from mood disorders, including depression, seasonal affective disorders and dysthmia, anxiety disorders including generalized anxiety disorder and panic disorder; agoraphobia, avoidant personality disorder; social phobia; obsessive compulsive disorder; post-traumatic stress disorder; memory disorders including dementia, amnestic disorders and age-associated memory impairment; disorders of eating behavior, including anorexia nervosa and bulimia nervosa; obesity; cluster headache; migraine; pain; Alzheimer's disease; chronic paroxysmal hemicrania; headache associated with vascular disorders; Parkinson's disease, including dementia in Parkinson's disease, neuroleptic-induced parkinsonism and tardive dyskinesias; endocrine disorders such as hyperprolactinaemia; vasospasm (particularly in the cerebral vasculature); hypertension; disorders in the gastrointestinal tract where changes in motility and secretion are involved; sexual dysfunction, including premature ejaculation; and chemical dependencies. Excerpt(s): The present invention relates to novel compositions containing the serotonin selective re-uptake inhibitor (SSRI) (1S-cis)-4-(3,4- dichlorophenyl)-1,2,3,4-tetrahydro-Nmethyl-1-naphthalenemine (hereinafter sertraline) and an agonist or antagonist of the serotonin 1 (5-HT.sub.1) receptor and to the use of such compositions for treating or preventing a condition selected from mood disorders, including depression, seasonal effective disorders and dysthmia, anxiety disorders including generalized anxiety disorder and panic disorder; agoraphobia, avoidant personality disorder; social phobia; obsessive compulsive disorder; post-traumatic stress disorder; memory disorders including dementia, amnestic disorders and age-associated memory impairment; disorders of eating behavior, including anorexia nervosa and bulimia nervosa; obesity; cluster headache; migraine; pain; Alzheimer's disease; chronic paroxysmal hemicrania; headache associated with vascular disorders; Parkinson's disease, including dementia in Parkinson's disease, neuroleptic-induced parkinsonism and tardive dyskinesias; endocrine disorders such as hyperprolactinaemia; vasospasm (particularly in the cerebral vasculature); hypertension; disorders in the gastrointestinal tract where changes

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in motility and secretion are involved; sexual dysfunction, including premature ejaculation; and chemical dependencies. U.S. Pat. No. 4,536,518 issued Aug. 20, 1985 refers to sertraline and derivatives thereof and states that these compounds are useful as antidepressant agents. U.S. Pat. No. 4,940,731 issued Jul. 10, 1990 refers to a method of treating premature ejaculation using sertraline. Web site: http://www.delphion.com/details?pn=US05597826__ •

Method for treating depression, obsessive compulsive disorder, and anxiety with N-acetyl serotonin Inventor(s): Oxenkrug; Gregory F. (Newton, MA), Requintina; Pura J. (West Kingston, RI) Assignee(s): St. Elizabeth's Medical Center of Boston (Boston, MA) Patent Number: 6,011,054 Date filed: November 4, 1998 Abstract: The present invention relates to a method of treatment of depression in a human being identified as having depression. This method comprises the administration of a therapeutically effective depression treatment amount of N-acetylserotonin (NAS), also referred to as N-acetyl-5-hydroxytryptamine, to a human being identified as having depression. The NAS may be administered alone or in combination with other agents, e.g., Ca.sup.++ antagonists. Excerpt(s): The present invention relates to a method of treatment of depression in a human being identified as having depression. This method comprises the administration of a therapeutically effective depression treatment amount of Nacetylserotonin (NAS) to a human being identified as having depression. NAS may be administered alone or in combination with other agents, e.g., Ca.sup.++ antagonists. Serotonin has been long ago considered to have the important role in the mechanism of antidepressant effect (see Lapin & Oxenkrug, 1969). Pineal gland has the highest concentration of serotonin in comparison with the other brain structures. Pineal serotonin is acetylated with the formation of N-acetylserotonin (NAS). NAS is further methylated by the hydroxy-indole-O-methyltransferase (HIOMT) to produce melatonin (5-methoxy-N-acetyltryptamine) (see Reiter, 1991). Melatonin exerted antidepressantlike activity in the "frog" test: potentiated the sedative effect of reserpine (Skene & Potgieter, 1981) and of selective MAO-A inhibitors (Requintina et al., 1994). We have recently observed the antidepressant-like activity of melatonin in the mouse tail suspension test (Prahie et al., in preparation). Selective MAO-A inhibitors (and some other antidepressants) stimulate the pineal NAS and melatonin production (Oxenkrug et al., 1994: see for rev. Oxenkrug, 1991). It was suggested that selective MAO-A inhibitors (and some other antidepressants) might correct the circadian rhythms abnormalities (and, thus, exert their antidepressant action) via their melatoninergic effects (Oxenkrug et al., 1986; see Oxenkrug, 1991). Although NAS was viewed mainly only as an intermediate product of melatonin biosynthesis from serotonin, it was reported that some of its effects (i.e., hypothermic and analgesic) differed (qualitatively or quantitatively) from that of serotonin and melatonin (Morton, 1987; Psarakis et al., 1988). Web site: http://www.delphion.com/details?pn=US06011054__

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Method of treating obsessive compulsive disorders, somatoform disorders, dissociative disorders, eating disorders, impulse control disorders, and autism Inventor(s): Coffin; Vicki L. (Basking Ridge, NJ) Assignee(s): Schering Corporation (Kenilworth, NJ) Patent Number: 6,410,527 Date filed: March 1, 1999 Abstract: A method for treating obsessive-compulsive disorders, somatoform disorders, dissociative disorders, eating disorders, impulse control disorders, and autism is disclosed. These disorders are treated by administering an effective amount of a D1/D5 antagonist. Excerpt(s): This invention is directed to the treatment of a group of disorders marked by repetitive, intrusive thoughts and/or ritualistic behaviors, i.e., obsessive-compulsive disorder, somatoform disorders, dissociative disorders, eating disorders, impulse control disorders, and autism. Obsessive-compulsive disorder ("OCD"), recognized to be among the most common of all psychiatric disorders, occurs in 2 to 3% of the U.S. population. OCD is characterized by anxiety-provoking and intrusive thoughts (e.g., fear of contamination and germs, doubt and uncertainty about future harm, need for symmetry, etc.) which lead to ritualistic and/or irrational behavior (e.g., constant checking, washing, touching, counting, etc.). See Hollander, et al., J. Clin Psychiatry 57 (Suppl. 8), pp. 3-6 (1996). Somatoform disorders (e.g., body dysmorphic disorder and hypochondriasis) are characterized by abnormal preoccupation with one's appearance or physical condition. For example, body dysmorphic disorder is a preoccupation with an imagined or slight defect in appearance. Many sufferers of body dysmorphic disorder are severely debilitated by their abnormal preoccupation, with significant impairment in social, occupational, or other important aspects of daily life. See Phillips, J. Clin Psychiatry 57 (suppl. 8), pp. 61-64 (1996). Hypocondriasis is characterized by a persistent conviction that one is, or is likely to become ill. Many hypochondriacs are unable to work or engage in ordinary activities due to their preoccupation with illness. Web site: http://www.delphion.com/details?pn=US06410527__

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Method of treating psychiatric diseases by neuromodulation within the dorsomedial thalamus Inventor(s): Kopell; Brian H. (New York, NY), Rezai; Ali R. (New York, NY) Assignee(s): ElectroCore Techniques, LLC (Summit, NJ) Patent Number: 6,609,030 Date filed: February 24, 2000 Abstract: A method for treating psychiatric diseases such as Affective Disorder (including Major Depression and Bipolar Disorder), Anxiety Disorder (including General Anxiety Disorder, Obsessive Compulsive Disorder and Panic Disorder) by stimulation (either electrical and/or chemical) of the thalamus, and in particular a region within the dorsomedial nucleus of the thalamus. The method includes the steps of determining a common group of patients, each suffering from a common specific diagnosis for a psychological disorder; determining which common region of the patients' thalami are involved in carrying the pathological electrical signals and/or metabolic activity which may otherwise be generated in dissimilar and disparate regions

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of the brains of the patients; surgically implanting an electrode and/or catheter and electrical signal generating device and/or drug pump such that the electrode and/or catheter is positioned within the region of the thalamus identified as the dorsomedial nucleus; and selectively adjusting the level of electrical and/or chemical stimulation in accordance with the specific effect of the stimulation of the patient. In particular, the region of the thalamus most frequently associated with the aforementioned psychiatric disease is the dorsomedial nucleus. Excerpt(s): This invention relates generally to the treatment of psychiatric disorders by stimulating appropriate regions of the thalamus, and more particularly to a method of modulating pathological electrical and/or chemical activity of the brain by electrical and/or chemical stimulation of the corresponding nucleus or nuclei of the thalamus, and most specifically to the stimulation of the dorsomedial nucleus of the thalamus. The treatment of psychiatric disorders by neurosurgical techniques has an extensive history. In the early 1930's Fulton and Jacobsen first recognized that an experimentally induced neurotic behavior in chimpanzees could be abolished by frontal lobectomy. Within a few years, Freeman and Watts developed the first psychosurgical procedure for humans known as the frontal lobotomy. As the inherent physiology of the frontal lobe became more evident, the original freehand procedure of Freeman and Watts became less and less extensive. By the late 1940's, the method of stereotaxis, in which the patient's brain is modeled in 3-dimensional space for exquisite targeting accuracy, merged with lesioning techniques resulting in an even more efficacious and safe psychosurgical procedure. Further developments of stereotactic equipment have combined with novel advancements in functional and anatomic imaging to encompass the state of the art in the neurosurgical treatment of psychiatric disorders today. However, the fundamental limitation of these lesioning techniques is that they are inherently irreversible and static in nature. There is no proverbial "off" switch to alleviate side effects and no way to adjust the desirable effects in response to a patient's changing symptom profile. Within the field of neurosurgery, the use of electrical stimulation for treating pathologies, including such disorders as compulsive eating, chronic pain, and movement disorders, such as Parkinson's disease essential tremor, has been widely discussed in the literature. It has been recognized that electrical stimulation holds significant advantages over alternative methods of treatment, for example lesioning, inasmuch as lesioning can only destroy nerve activity. In many instances, the preferred effect is to stimulate or reversibly block nervous tissue. Electrical stimulation permits such stimulation of the target neural structures, and equally importantly, it does not require the destruction of the nervous tissue (it is a reversible process, which can literally be shut off or removed at will). Web site: http://www.delphion.com/details?pn=US06609030__ •

Method of treating schizophrenia, tourette's syndrome, mania, autism, and obsessive compulsive disorder with inhibitors of brain nitric oxide synthase Inventor(s): Freeman; Bobby L. (Little Rock, AR), Karson; Craig N. (Little Rock, AR), Lyon; Melvin (Little Rock, AR) Assignee(s): University of Arkansas (Little Rock, AR) Patent Number: 5,527,825 Date filed: April 6, 1994 Abstract: The present invention provides a pharmaceutical compositions suitable for the treatment of brain diseases characterized by excessive activity of brain dopamine

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systems and/or nitric oxide systems. Also provided is a method of treating psychiatric and neurologic diseases. Excerpt(s): The present invention relates generally to the fields of biological psychiatry and neuropharmacology. More specifically, the present invention relates to a novel method of treating dysfunctional dopaminergic and nitric oxide related activity and related psychiatric and neurologic diseases. A wide variety of psychiatric and neurologic pathophysiologic states are believed to involve dysfunction of brain neurotransmitter and neuropeptide systems. A monoaminergic neurotransmitter that has drawn considerable attention over the last generation is dopamine. Antidopaminergic drugs, such as the neuroleptics haloperidol and chlorpromazine, have been the drugs of choice for various psychiatric and neurologic diseases such as schizophrenia. Despite moderate success, the antipsychotic dopamine antagonists have serious medical drawbacks including the gradual induction of permanent dyskinesias and a failure to counteract abnormal cholinergic interactions with dopamine. Thus, safer and more efficacious means of treating diseases such as schizophrenia are highly desirable. A salient animal model has recently been developed for certain aspects of schizophrenic behavior and brain pathology. This animal model involves prenatal exposure to d-amphetamine in the rat in which there are early juvenile signs of behavioral changes suggestive of hypodopaminergia, followed by an increasing sensitivity to ultradian rhythm changes in striatal dopamine activity. As the offspring approach adulthood, there are significant increases in bodily activity, suggesting increased dopamine activity in the postpubertal period. There are also gradual increases in switching between alternative response possibilities, poorer reversal learning and finally increased perseveration in simple response, all of which have been characterized not only as functions of dopamine overstimulation in animals and humans but also as significant symptoms in schizophrenic patients. Web site: http://www.delphion.com/details?pn=US05527825__ •

Nicotine antagonists for nicotine-responsive neuropsychiatric disorders Inventor(s): Sanberg; Paul R. (Spring Hill, FL), Shytle; Roland D. (Lutz, FL), Silver; Archie A. (Tampa, FL) Assignee(s): University of South Florida (Tampa, FL) Patent Number: 6,034,079 Date filed: November 23, 1998 Abstract: Nicotine-responsive neuropsychiatric disorders can be treated by administering a nicotine antagonist, particularly mecamylamine. Combination therapy of mecamylamine with a neuroleptic drug also is disclosed. The neuropsychiatric disorders include Tourette's syndrome, schizophrenia, depression, bipolar disorder, tremors, attention deficit hyperactivity disorder, obsessive-compulsive disorder, hemidystonia, rage outbursts and tardive dyskinesia. Excerpt(s): The present invention is in the field of pharmacotherapy of nicotineresponsive neuropsychiatric disorders by administering a nicotine antagonist alone, particularly mecamylamine, or in combination with a neuroleptic agent. Examples of such disorders are schizophrenia, bipolar disorder, obsessive compulsive disorder, attention deficit hyperactivity disorder, Tourette's syndrome, and other movement disorders. Tourette's syndrome (TS) is an autosomal dominant neuropsychiatric disorder characterized by a range of symptoms, including multiple motor and phonic

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tics. It is a hyperkinetic movement disorder expressed largely by sudden, rapid, brief, recurrent, nonrhythmic, stereotyped motor movements (motor tics) or sounds (phonic tics), experienced as irresistible impulses but which can be suppressed for varying lengths of time (Tourette Syndrome Classification Study Group, Arch Neurol 50: 101316). Motor tics generally include eye blinking, head jerking, shoulder shrugging and facial grimacing, while phonic or vocal tics include throat clearing, sniffling, yelping, tongue clicking and coprolalia. The symptoms typically begin in childhood and range from relatively mild to very severe over the course of a patient's lifetime (Robertson M M, Br J Psychiatry, 154:147-169, 1989). Many TS patients also exhibit other neuropsychiatric abnormalities including obsessive compulsive symptoms (Pauls D L et al. Psychopharm Bull, 22:730-733, 1986), hyperactivity and attention deficits (Comings D E, Himes J A, Comings B G, J Clin Psychiatry, 51:463-469, 1990). Problems with extreme temper or aggressive behavior also are frequent (Riddle M A et al. Wiley Series in Child and Adolescent Mental Health, Eds. Cohen D J, Bruun, R D, Leckman J F, New York City, John Wiley and Sons, pp. 151-162, 1988; Stelf M E, Bornstein R A, Hammond L, A survey of Tourette syndrome patients and their families: the 1987 Ohio Tourette Survey, Cincinnati, Ohio Tourette Syndrome Association, 1988), as are school refusal and learning disabilities (Harris D, Silver A A, Learning Disabilities, 6(1):1-7, 1995; Silver A A, Hagin R A, Disorders of Learning Childhood, Noshpitz J D, ed. New York City: Wiley, pp. 469-508, 1990). While the pathogenesis of TS is still unknown, excessive striatal dopamine and/or dopamine receptor hypersensitivity has been proposed (Singer H S et al. Ann Neurol, 12:361-366, 1982), based largely on the therapeutic effectiveness of dopamine receptor antagonists. T S is frequently treated with the dopamine antagonist haloperidol (Haldol.RTM., McNeil Pharmaceutical, Raritan, N.J.), which is effective in about 70% of cases (Erenberg G, Cruse R P, Rothner, A D, Ann Neurol, 22:383-385, 1987; Shapiro A K, Shapiro E, Wiley series in child and adolescent mental health, Eds. Cohen D J, Bruun R D, Leckman J F, New York City, John Wiley and Sons, pp. 267-280, 1988). Other neuroleptics include pimozide (Shapiro E S et al. Arch Gen Psychiatry, 46:722-730, 1989), fluphenazine (Singer H S, Gammon K, Quaskey S. Pediat Neuroscience, 12:71-74, 1985-1986), and risperidone (Stamenkovic et al., Lancet 344:1577-78, 1994). An alternative medication frequently employed is the.alpha.adrenergic agonist clonidine, which also is effective for associated attention deficit hyperactivity disorder (ADHD) but has only a 40% success rate for motor and vocal tics (Bruun R D, J Am Acad Child Psychiatry, 23: 126-133, 1984; Cohen D J et al. Arch Gen Psychiatry 37: 1350-1357, 1980). Other medications that have been used with varying degrees of effectiveness include clonazepam (Gonce M, Barbeau A. Can J Neurol Sci 4:279-283, 1977), naloxone (Davidson P W et al. Appl Res Ment Retardation 4: 1-4, 1983) and fluoxetine (Riddle M A et al. J Am Acad Child Adol Psychiatry 29: 45-48, 1990). One of the most commonly used medications is haloperidol (Erenberg G, Cruse R P, Rothner A D, Ann Neurol, 22:383-385, 1987). However, therapeutic doses of haloperidol have frequent side effects that affect compliance, including difficulty in concentration, drowsiness, depression, weight gain, parkinsonian-like symptoms--and with long-term use--tardive dyskinesia (Shapiro A K, Shapiro E, Tourette's syndrome and Tic Disorders: Clinical Understanding and Treatment. Wiley series in child and adolescent mental health. Eds. Cohen, D J, Bruun, R D, Leckman J F, New York City, John Wiley and Sons, pp. 267-298, 1988). The side effect of tardive dyskinesia is particularly bothersome because it may add additional abnormal, involuntary movements of the tongue, jaw, trunk and/or extremities. Web site: http://www.delphion.com/details?pn=US06034079__

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Reboxetine for treatment obsessive compulsive disorders and panic disorder Inventor(s): Dubini; Adriana (Milan, IT), McCall; John Michael (Kalamazoo, MI), Taylor; Duncan Paul (Kalamazoo, MI), Von Voigtlander; Philip F. (Plainwell, MI), Wong; Erik Ho Fong (Portage, MI) Assignee(s): Pharmacia and Upjohn Company (Kalamazoo, MI) Patent Number: 6,391,876 Date filed: October 19, 2000 Abstract: This invention relates to the use of reboxetine in the treatment of Obsessive Compulsive Disorders and Panic Disorders. Excerpt(s): This invention describes new treatments for several nervous system disorders, including: Obsessive Compulsive Disorders, and panic Disorder. The treatment involves the administration of the drug reboxetine. The introduction of tricyclic antidepressants in the early 1960s has provided a major advance in the treatment of neuropsychiatric disorders. Reactive and endogenous depressions, diagnoses formerly carrying grave prognostic implications, have become, with the introduction of the tricyclic, manageable disorders with a much smaller toll on the patient and the society as a whole. The early tricyclic compounds were reuptake inhibitors of all the catecholamines released in the synaptic cleft, thus resulting in prolongation and enhancement of the dopamine (DA), noradrenaline (NA) and serotonin (5-hydroxytryptamine=5-HT) action. Lack of selectivity also causes undesired side effects particularly on the acetylcholine (especially the muscarinic component), and histamine mediated neurotransmission. Web site: http://www.delphion.com/details?pn=US06391876__

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Treatment of anxiety disorders Inventor(s): Amrein; Roman (31 Landhausweg, CH-4126 Bettingen, CH), Versiani; Marcio (Avda. Copacabana 1133, S. 1303, BR-22070 Rio de Janeiro, BR) Assignee(s): none reported Patent Number: 5,371,082 Date filed: September 14, 1993 Abstract: The invention relates to the use of p-chloro-N-(2-morpholinoethyl)benzamide in the treatment of anxiety disorders, such as, panic disorders, social phobia and obsessive compulsive disorder, Excerpt(s): The invention relates to the use of p-chloro-N-(2morpholinoethyl)benzamide [also known as moclobemide] in the treatment of anxiety disorders, such as, panic disorders, social phobia and obsessive disorders. Depressive and anxiety symptoms frequently overlap. Efficacy of tricyclic antidepressants (TCAs) and classical irreversible monoamine oxidase inhibitors (MAOIs) in anxiety disorders has been demonstrated in results from clinical trials and case reports. The anxiolytic effects of antidepressants are widely believed to be specific and not an epiphenomenon of antidepressant or patholytic effects. In long term treatment, tricyclic antidepressants (TCAs) appear to be effective. However, the poor tolerance of TCAs and the risks associated with conventional irreversible MAOIs are limitations to their usefulness. Therefore, there is a strong demand for alternative drugs particularly for chronic and long term treatment.

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Web site: http://www.delphion.com/details?pn=US05371082__ •

Use of 5-HT.sub.3 receptor antagonists in treating panic disorders or obsessive compulsive disorders Inventor(s): Azcona; Alberto E. (Basel, CH), Taylor; Pamela (Basel, CH) Assignee(s): Sandoz Ltd. (Basel, CH) Patent Number: 5,530,008 Date filed: January 24, 1994 Abstract: 5-HT.sub.3 Receptor antagonists are useful in treating panic disorders or obsessive compulsive disorders. Excerpt(s): The present invention relates to a new use, in particular a new pharmaceutical use, for the compound group comprising 5HT.sub.3 receptor antagonists, said compound group being referred to hereinafter collectively as COMPOUNDS OF THE INVENTION. 5-HT.sub.3 receptor antagonists are a well known class of compounds. Spatial models for 5-HT.sub.3 receptors and 5-HT.sub.3 antagonists have been proposed recently by M. F. Hibert and S. Peroutka. They are typically compounds which act on 5-HT.sub.3 receptors on the e.g. isolated rabbit heart or vagus nerve by antagonizing the action of 5-HT thereon. They may have a pA.sub.2 greater than 6 or preferably more than 8 or 9.5-HT.sub.3 antagonists may be selective for 5-HT.sub.3 receptors as compared to other serotonin receptors or dopamine receptors. vi) a compound specifically or generically disclosed in DE 3,740,352 A, WO 8803801 A, EP 266,899 A, GB 2,192,885 A, GB 2,208,862 A, EP 219,929 A, EP 219,193 A, EP 212,398 A, EP 210,840 A, EP 191,562 A, EP 248,843 A, WO 89/09217, the contents of which are incorporated herein by reference. Web site: http://www.delphion.com/details?pn=US05530008__

Patent Applications on Obsessive Compulsive Disorder As of December 2000, U.S. patent applications are open to public viewing.10 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take several years.) The following patent applications have been filed since December 2000 relating to obsessive compulsive disorder: •

Antidepressant azaheterocyclylmethyl derivatives of oxaheterocycle-fused-[1,4]benzodioxans Inventor(s): Gao, Hong; (Plainsboro, NJ), Gildersleeve, Elizabeth S.; (San Diego, CA), Stack, Gary P.; (Ambler, PA) Correspondence: Wyeth; Patent Law Group; Five Giralda Farms; Madison; NJ; 07940; US Patent Application Number: 20020183353 Date filed: April 24, 2002

10

This has been a common practice outside the United States prior to December 2000.

Patents 119

Abstract: Compounds of the formula 1useful for the treatment of depression such as obsessive compulsive disorder, panic attacks, generalized anxiety disorder, social anxiety disorder, sexual dysfunction, eating disorders, obesity, addictive disorders caused by ethanol or cocaine abuse and related illnesses Excerpt(s): This application claims priority from co-pending provisional application serial No. 60/286,569, filed on Apr. 26, 2001, the entire disclosure of which is hereby incorporated by reference. Major depression is a serious health problem affecting more than 5% of the population, with a life-time prevalence of 15-20%. Selective serotonin reuptake inhibitors have produced significant success in treating depression and related illnesses and have become among the most prescribed drugs. They nonetheless have a slow onset of action, often taking several weeks to produce their full therapeutic effect. Furthermore, they are effective in fewer than two-thirds of patients. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Arylsulphonyl substituted-tetrahydro- and hexahydro-carbazoles Inventor(s): Fu, Jian-Min; (Kalamazoo, MI) Correspondence: Flynn, Thiel, Boutell & Tanis, P.C.; 2026 Rambling Road; Kalamazoo; MI; 49008-1699; US Patent Application Number: 20030100596 Date filed: October 8, 2002 Abstract: The invention provides compounds of formula I for use in treating conditions in which 5-HT.sub.6 receptors are involved such as in anxiety, depression, schizophrenia, Alzheimer's disease, stress-related disease, panic, a phobia, obsessive compulsive disorder, obesity, post-traumatic stress syndrome, epilepsy, and other CNS disorders. 1 Excerpt(s): This application claims the benefit of U.S. provisional application Serial No. 60/327,876 and U.S. provisional application Serial No. 60/327,875, both filed on Oct. 9, 2001, under 35 USC 119(e)(i), which are incorporated herein by reference in their entirety. The present invention relates to substituted 6-arylsulphonyl tetrahydro- and hexahydro-carbazoles which are serotonin receptor, 5-HT.sub.6, ligands and are useful for treating anxiety, depression, schizophrenia, Alzheimer's disease, stress-related disease, panic, a phobia, obsessive compulsive disorder, obesity, post-traumatic stress syndrome, epilepsy, and other central nervous system (CNS) disorders in humans and animals. Serotonin has been implicated in a number of diseases, disorders, and conditions that originate in the CNS. Serotonin also plays an important role in peripheral systems, such as the gastrointestinal system, where it has been found to mediate a variety of contractile, secretory, and electrophysiological effects. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Combination treatment for anxiety, depression, obsessive compulsive disorder and psychosis Inventor(s): Howard, Harry R. JR.; (Bristol, CT) Correspondence: Pfizer Inc; 150 East 42nd Street; 5th Floor - Stop 49; New York; NY; 10017-5612; US Patent Application Number: 20020123490 Date filed: December 6, 2001 Abstract: The present invention relates to a method of treating depression, obsessive compulsive disorder and psychosis in a mammal, including a human, by administering to the mammal an atypical antipsychotic in combination with an antidepressant agent with improvement in efficiency. It also relates to pharmaceutical compositions containing a pharmaceutically acceptable carrier, an atypical antipsychotic, and an SRI. Excerpt(s): The present invention relates to a method of treating depression, obsessive compulsive disorder (OCD) and psychosis with improved efficacy in a mammal, including a human, by administering to the mammal an atypical antipsychotic agent in combination with a serotonin reuptake inhibitor (SRI). It also relates to pharmaceutical compositions containing a pharmaceutically acceptable carrier, an atypical antipsychotic agent and a serotonin reuptake inhibitor (SRI). Major depression is characterized by feelings of intense sadness and despair, mental slowing and loss of concentration, pessimistic worry, agitation, and self-deprecation. Physical changes also occur, especially in severe or "melancholic" depression. These include insomnia or hypersomnia, anorexia and weight loss (or sometimes overeating), decreased energy and libido, and disruption of normal circadian rhythms of activity, body temperature, and many endocrine functions. Serotonin Selective Reuptake Inhibitors (SSRIs) currently provide efficacy in the treatment of major depressive disorder (MDD) and are generally perceived by psychiatrists and primary care physicians as effective, well-tolerated and easily administered. However, they are associated with undesirable features, such as high incidence of sexual dysfunction, delayed onset of action and a level of nonresponsiveness estimated to be as high as 30% (see M. J. Gitlin, Journal of Clinical Psychiatry, 1994, 55, 406-413 and R. T. Segraves, Journal of Clinical Psychiatry, 1992, 10(2), 4-10). Preclinical and clinical evidence has indicated that the sexual dysfunction associated with SSRI therapy can be reduced through the use of monoamine reuptake inhibitors (SRI) and dopamine reuptake inhibitors (DRIs), such as bupropion (see A. K. Ashton, Journal of Clinical Psychiatry, 1998, 59(3), 112-115). Furthermore, the combination of SRI and DRI may hasten the onset of action as well as offering relief to refractory patients, possibly through a synergistic mechanism (see R. D. Marshall et al, Journal of Psychopharmacology, 1995, 9(3), 284-286) and prove beneficial in the treatment of substance abuse and attention deficit hyperactivity disorder (ADHD) according to Barrickman et al, Journal of the American Academy of Child and Adolescent Psychology, 1995, 34(5), 649 and Shekim et al, Journal of Nervous and Mental Disease, 1989, 177(5), 296. Their utility in OCD is inferred from D. J. Stein et al., Journal of Clinical Psychiatry, 1997,58(3), 119. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

Patents 121

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Cyclopenta[b][1,4]diazepino[6,7,1-hi]indoles and derivatives Inventor(s): Nelson, James A.; (Washington Crossing, PA), Rosenzweig-Lipson, Sharon J.; (East Brunswick, NJ), Sabalski, Joan E.; (Yardville, NJ), Sabb, Annmarie L.; (Pennington, NJ), Vogel, Robert L.; (Stratford, NJ), Welmaker, Gregory S.; (Jackson, NJ) Correspondence: Steven R. Eck; American Home Products Corporation; Patent Law Department - 2B; Five Giralda Farms; Madison; NJ; 07940; US Patent Application Number: 20020107242 Date filed: November 2, 2001 Abstract: This invention provides compounds of the formulae: 1wherein:R.sub.1 is hydrogen, --C(O)CH.sub.3 or alkyl of 1-6 carbon atoms;R.sub.2 and R.sub.3 are each, independently, hydrogen, alkyl of 1-6 carbon atoms, cycloalkyl, alkoxy of 1-6 carbon atoms, --CH.sub.2OH, fluoroalkyl, alkyl sulfonamide of 1-6 carbon atoms, alkyl amide of 1-6 carbon atoms, amino, alkylamino of 1-6 carbon atoms, dialkylamino of 1-6 carbon atoms per alkyl moiety, fluoroalkoxy of 1-6 carbon atoms, acyl of 2-7 carbon atoms, aryl, or aroyl;R.sub.4 and R.sub.5 are each, independently, hydrogen, alkyl of 1-6 carbon atoms, alkoxy of 1-6 carbon atoms, halogen, fluoroalkyl, --CN, alkyl sulfonamide of 1-6 carbon atoms, alkyl amide of 1-6 carbon atoms, amino, alkylamino of 1-6 carbon atoms, dialkylamino of 1-6 carbon atoms per alkyl moiety, fluoroalkoxy of 1-6 carbon atoms, acyl of 2-7 carbon atoms, or aroyl;R.sub.6 and R.sub.7 are each independently hydrogen, C.sub.1-C.sub.6 alkyl or cycloalkyl;or a pharmaceutically acceptable salt thereof, as well as pharmaceutical compositions containing these compounds and methods for their use, including treatment of obsessive-compulsive disorder, panic disorder, depression, anxiety, generalized anxiety disorder, schizophrenia, migraine, sleep disorders, eating disorders, obesity, epilepsy, and spinal cord injury. Excerpt(s): This application claims priority from copending provisional application Serial No. 60/245,593, filed Nov. 3, 2000, the entire disclosure of which is hereby incorporated by reference. The present invention relates to cyclopenta[b][1,4]diazepino[6,7,1-- hi]indoles and derivatives thereof, which are serotonin 5-hydroxytryptamine 2.sub.c (5HT.sub.2c) receptor agonists useful for the treatment of central nervous system disorders including, but not limited to, obsessivecompulsive disorder, depression, anxiety, generalized anxiety disorder, schizophrenia, panic disorder, migraine, sleep disorders, such as sleep apnea, eating disorders, such as hyperphagia, obesity, epilepsy, and spinal cord injury. Obesity is a medical disorder characterized by an excess of body fat or adipose tissue. Comorbidities associated with obesity are Type II diabetes, cardiovascular disease, hypertension, hyperlipidemia, stroke, osteoarthritis, sleep apnea, gall bladder disease, gout, some cancers, some infertility, and early mortality. As the percentage of obese individuals continues to rise both in the U.S. and abroad, obesity is expected to be a major health risk in the 21.sup.st Century. The serotonin 5-hydroxytryptamine (5-HT) receptor is a G-protein coupled receptor which is expressed in neurons in many regions of the human central nervous system. [Wilkinson, L. O. and Dourish, C. T. in Serotonin Receptor Subtypes: Basic and Clinical Aspects (ed. Peroutka, S. J. ) 147-210 (Wiley-Liss, N.Y., 1991).] The 5HT.sub.2c receptor (formerly called the 5HT.sub.1C receptor) is a prominent subtype of the serotonin receptor found in the central nervous system of both rats and humans. It is expressed widely in both cortical and subcortical regions. [Julius, D. MacDermott, A. B., Axel, R. Jessell, T. M. Science 241:558-564 (1988).] Studies in several animal species and in humans have shown that the non-selective 5HT.sub.2C receptor agonist, metachlorophenylpiperazine (MCPP) decreases food intake. [Cowen, P. J., Clifford, E. M., Williams, C., Walsh, A. E. S., Fairburn, C. G. Nature 376: 557 (1995).] Tecott, et al have

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demonstrated that transgenic mice lacking the 5HT.sub.2C receptor eat more and are heavier than Wild Type mice. [Tecott, L. H., Sun, L. M., Akana, S. F., Strack, A. M., Lowenstein, D. H., Dallman, M. F., Jullus, D. Nature 374: 542-546 (1995).] Compounds of this invention are 5HT.sub.2C receptor subtype selective agonists which are selective over other monoamine receptors, causes a reduction in food intake and result in a reduction in weight gain. Other therapeutic indications for 5HT.sub.2C agonists are obsessive compulsive disorder, depression, panic disorder, schizophrenia, sleep disorders, eating disorders, and epilepsy. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Materials and methods for the treatment of depression Inventor(s): Druzgala, Pascal; (Santa Rosa, CA) Correspondence: Saliwanchik Lloyd & Saliwanchik; A Professional Association; 2421 N.W. 41st Street; Suite A-1; Gainesville; FL; 326066669 Patent Application Number: 20030078284 Date filed: October 18, 2002 Abstract: The subject invention provides compounds which are easily metabolized by the metobolic drug detoxification systems. Particularly, fluvoxamine analogs which have been designed to include esters within the structure of the compounds are taught. Also provided are methods of treating depression and affective disorders, such as obsessive compulsive disorder. Pharmaceutical compositions of the fluvoxamine analogs are also taught. Excerpt(s): This application is a continuation of U.S. Ser. No. 09/841,749, filed Apr. 24, 2001; which claims priority from provisional patent application U.S. Ser. No. 60/199,343, filed Apr. 24, 2000. Major depression represents one of the most common mental illness, affecting between 5- 10% of the population. The disease is characterized by extreme changes in mood which may also be associated with psychoses. It has generally been found that most antidepressant agents exert significant effects on the regulation of monoamine neurotransmitters, including serotonin. A number of types of antidepressants have been developed in recent years. Many of these compounds regulate serotonin (5-hydroxytryptamine; 5-HT). Trazodone controls the actions of 5-HT while fluoxetine is a potent and selective inhibitor of 5-HT reuptake. 3Chloroimipramine which inhibits both 5-HT and norepinephrine reuptake has been extensively used as an antidepressant in Europe and Canada. Other compounds which are of current interest or have been examined as antidepressants include fluvoxamine, citalopram, zimeldine, sertraline, bupropion and nomifensine. Fluvoxamine facilitates serotoninergic neurotransmission via potent and selective inhibition of scrotonin reuptake into presynaptic neurons. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Methods of determining susceptibility to or presence of schizophrenia, or a disorder related thereto Inventor(s): Gogos, Joseph A.; (New York, NY), Karayiorgou, Maria; (New York, NY) Correspondence: Klauber & Jackson; 411 Hackensack Avenue; Hackensack; NJ; 07601 Patent Application Number: 20020193581 Date filed: April 10, 2002 Abstract: Variations in the DNA sequence of the human proline dehydrogenase gene (PRODH) which correlate to an increased susceptibility to, or presence of schizophrenia or a disease or disorder related thereto, such as obsessive compulsive disorder (OCD), bipolar disorder (BP), or major depressive disorder (MDD) are provided, along with assays to diagnosing schizophrenia or a disease or disorder related thereto, and evaluating potential drugs or agents for using in treating such diseases or disorders. Excerpt(s): This Application is a continuation-in-part of copending U.S. application Ser. No. 09/229,530 entitled "Methods of Determining Susceptibility to or presence of schizophrenia, or a disorder related thereto", which is hereby incorporated by reference in its entirety. The present invention relates to isolated nucleic acid molecules which encode human and murine proline dehydrogenase, and methods for determining susceptibility to, or the presence of schizophrenia or a disease or disorder related thereto, such as obsessive compulsive disorder, bipolar disorder (BP), or major depressive disorder in a subject by determining levels of proline dehydrogenase (PRODH) in a bodily sample. Furthermore, the present invention comprises polymorphisms of the human proline dehydrogenase (PRODH) gene which correlate to a phenotype closely related to schizophrenia or a disease or disorder related thereto. The present invention also relates to various assays for drugs or agents that can treat schizophrenia or a disease or disorder related thereto. It has been posited that the amino acid proline serves as a modulator of synaptic transmission in the mammalian brain, due to the selective expression of a brain specific high affinity proline transporter in a subset of glutamatergic pathways (Fremeau et al., 1996). Proline transporter is modulated by enckephalins, the expression of which may be decreased in the brains of patients with schizophrenia and elevated proline concentration. Furthermore, recent analysis indicates that endogenous extracellular proline may regulate the basal function of some glutamate synapses by maintaining them in a partially potentiated state. Also, elevated proline concentration has also been previously associated with behavioral and neurological effects. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Novel cyclohexenyl phenyl diazepines vasopressin and oxytocin receptor modulators Inventor(s): Failli, Amedeo Arturo; (Princeton Junction, NJ), Sanders, William Jennings; (Fox Lake, IL), Trybulski, Eugene John; (Princeton Junction, NJ) Correspondence: Arnold S. Milowsky; 5 Giralda Farms; Madison; NJ; 07940; US Patent Application Number: 20020198196 Date filed: April 10, 2002 Abstract: The present invention provides novel tricyclic diazepine compounds and methods and pharmaceutical compositions utilizing them for the treating or preventing disorders including diabetes insipidus, nocturnal enuresis, nocturia, urinary

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incontinence, bleeding and coagulation disorders, congestive heart failure or for inducing temporary delay of urination, and in conditions with increased vascular resistance and coronary vasoconstriction; and for the treating or preventing disorders remedied or alleviated by oxytocin antagonist activity, including suppression of preterm labor, dysmenorrhea, endometritis, and for suppressing labor at term prior to caesarean delivery. These compounds are also useful in enhancing fertility rates, enhancing survival rates and synchronizing estrus in farm animals; and treatment of disfunctions of the oxytocin system in the central nervous system including obsessive compulsive disorder (OCD) and neuropsychiatric disorders. Excerpt(s): This application claims priority from copending provisional application Serial No. 60/283,265, filed Apr. 12, 2001, the entire disclosure of which is hereby incorporated by reference. This invention concerns novel tricyclic diazepines with affinity for the vasopressin and/or oxytocin receptors which can act as modulators of vasopressin and/or oxytocin effects in vivo, as well as methods of their manufacture, methods of treatment and pharmaceutical compositions utilizing these compounds. The compounds of the present invention are useful therapeutic agents for treating conditions in mammals, particularly in humans where decreased levels of vasopressin are desired, such as in congestive heart failure, in disease conditions with excessive renal water reabsorption and in conditions with increased vascular resistance and coronary vasoconstriction. They are also useful therapeutic agents for treating diseases in mammals, particularly humans, affecting the vasopressin system which are characterized by excretion of excessive volumes of diluted urine, including central or nephrogenic diabetes insipidus, for treating nocturnal enuresis, nocturia, urinary incontinence, bleeding and coagulation disorders, or temporary delay of urination. By preventing oxytocin from binding to its receptors they are useful in the prevention and/or suppression of preterm labor, for the suppression of labor at term prior to caesarean delivery, to facilitate transport to a medical facility, and for the treatment of dysmenorrhea. They are also useful in enhancing fertility rates, enhancing survival rates and synchronizing estrus in farm animals; and they may be useful in the prevention and treatment of disfunctions of the oxytocin system in the central nervous system, including obsessive compulsive disorder (OCD) and neuropsychiatric disorders. Vasopressin is involved in some cases of congestive heart failure where peripheral resistance is increased. The hormone exerts its action through two well defined receptor subtypes: vascular V.sub.1a and renal epithelial V.sub.2 receptors. V.sub.1a receptor antagonists may decrease systemic vascular resistance, increase cardiac output and prevent vasopressin induced coronary vasoconstriction. Thus, in conditions with vasopressin induced increases in total peripheral resistance and altered local blood flow, V.sub.1a receptor antagonists may be therapeutically useful agents. V.sub.1a receptor antagonists may decrease blood pressure, induce hypotensive effects and thus be therapeutically useful in treatment of some types of hypertension. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

Patents 125

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Novel heteroaryl derivatives, their preparation and use Inventor(s): Andersen, Kim; (Virum, DK), Krog-Jensen, Christian; (Copenhagen, DK), Mikkelsen, Gitte; (Ballerup, DK), Mikkelsen, Ivan; (Koge, DK), Moltzen, Ejner Knud; (Gentofte, DK), Rottlander, Mario; (Valby, DK), Ruhland, Thomas; (Valby, DK) Correspondence: Darby & Darby P.C.; 805 Third Avenue; New York; NY; 10022; US Patent Application Number: 20030050306 Date filed: June 25, 2002 Abstract: A heteroaryl derivative having the formula (I) 1any of its enantiomers or any mixture thereof, wherein X is --O--, --S--, or CR.sup.4R.sup.5--; and Y is -CR.sup.6R.sup.7; --CR.sup.6R.sup.7--CR.s- up.8R.sup.9--, or --CR.sup.6--CR.sup.7; or X and Y together form a group --CR.sup.4.dbd.R.sup.5--, or --CR.sup.4.dbd.CR.sup.5-CR.sup.6R.sup.7--; Z is --O--, or --S--; W is N, C, or CH; n is 2, 3, 4, 5, 6, 7, 8, 9 or 10; m is 2 or 3; A is O or S wherein the doted lines mean an optional bond. The compounds of the invention are considered useful for the treatment of affective disorders such as general anxiety disorder, panic disorder, obsessive compulsive disorder, depression, social phobia and eating disorders, and neurological disorders such as psychosis. Excerpt(s): This application is a Continuation of International Application No. PCT/DK00/00741, filed Dec. 29, 2000. The disclosure of the prior application is hereby incorporated by reference. The present invention relates to novel heteroaryl derivatives potently binding to the 5-HT.sub.1A receptor, pharmaceutical compositions containing these compounds and the use thereof for the treatment of certain psychiatric and neurological disorders. The compounds of the invention are also potent dopamine D.sub.4 receptor ligands and are considered to be particularly useful for the treatment of depression and psychosis. Furthermore, many compounds of the invention have potent serotonin reuptake inhibition activity and/or effect at dopamine D.sub.3 receptors. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Novel tricyclic diazepines tocolytic oxytocin receptor antagonists Inventor(s): Caggiano, Thomas Joseph; (Morrisville, PA), Failli, Amedeo Arturo; (Princeton Junction, NJ), Memoli, Kevin Anthony; (Cranbury, NJ), Sabatucci, Joseph Peter; (Collegeville, PA), Shumsky, Jay Scott; (Hightstown, NJ), Trybulski, Eugene John; (Princeton Junction, NJ) Correspondence: Arnold S. Milowsky; 5 Giralda Farms; Madison; NJ; 07940; US Patent Application Number: 20030008863 Date filed: April 10, 2002 Abstract: This invention provides novel tricyclic diazepine compounds as well as methods and pharmaceutical compositions utilizing these compounds for the treatment and/or prevention and/or suppression of disorders which may be remedied or alleviated by oxytocin antagonist activity, including treatment of preterm labor, dysmenorrhea, endometritis, and for suppressing labor prior to caesarean delivery. These compounds are also useful in enhancing fertility rates, enhancing survival rates and synchronizing estrus in farm animals; and may be useful in the prevention and treatment of disfunctions of the oxytocin system in the central nervous system including obsessive compulsive disorder (OCD) and neuropsychiatric disorders.

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Excerpt(s): This invention concerns novel tricyclic diazepines which act as competitive oxytocin receptor antagonists, as well as methods of their manufacture, methods of treatment and pharmaceutical compositions utilizing these compounds. The compounds of the present invention are useful therapeutic agents in mammals, particularly in humans. More specifically, they can be used in the prevention and/or suppression of preterm labor, for the suppression of labor at term prior to caesarean delivery, to facilitate antinatal transport to a medical facility, and for the treatment of dysmenorrhea. These compounds also useful in enhancing fertility rates, enhancing survival rates and synchronizing estrus in farm animals; and may be useful in the prevention and treatment of disfunctions of the oxytocin system in the central nervous system including obsessive compulsive disorder (OCD) and neuropsychiatric disorders. Premature labor remains the leading cause of perinatal mortality and morbidity. Infant mortality dramatically decreases with increased gestational age. The survival rate of prematurely born infants increases from 20% at 24 weeks to 94% at 30 weeks. Moreover the cost associated with the care of an infant born prematurely is extremely high. While many agents have been developed for the treatment of premature labor in the last 40 years, the incidence of pre-term births and low birth weight infants has remained relatively unchanged. Therefore there remains an unmet need for the development of a safe and effective treatment of preterm labor. Tocolytic (uterine relaxing) agents currently in use include.beta.sub.2 adrenergic receptor agonists such as Ritodrine which is moderately effective in suppressing preterm labor, but it is associated with maternal hypotension, tachycardia, and metabolic side effects. Several other agents have been used to suppress premature labor, including other.beta.sub.2 adrenergic agonists (terbutaline, albuterol), magnesium sulfate, NSAIDs (indomethacin), and calcium channel blockers. The consensus is that none of these agents are very effective; there is no clinical evidence showing that these compounds can prolong gestation for more than 7 days (Johnson, Drugs, 45, 684-692 (1993)). Furthermore, their safety profile is not ideal. Adverse effects include respiratory depression and cardiac arrest (magnesium sulfate), hemodynamic effects (calcium channel blockers), premature closure of the ductus arteriosus and oligohydramnios (NSAIDs; prostaglandin synthase inhibitors). Therefore, there is an unmet need for safer and more efficacious agents for the treatment of preterm labor with better patient tolerability. Specific requirements with regard to safety include a product with no or low rates of tachycardia, limited anxiety, improved fetal safety, and few, if any, adverse cardiovascular effects. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Novel tricyclic hydroxy carboxamides and derivatives thereof tocolytic oxytocin receptor antagonists Inventor(s): Arturo Failli, Amedeo; (Princeton Junction, NJ), Caggiano, Thomas Joseph; (Morrisville, PA), Memoli, Kevin Anthony; (Cranbury, NJ), Sabatucci, Joseph Peter; (Collegeville, PA), Sanders, William Jennings; (Fox Lake, IL), Shumsky, Jay Scott; (Hightstown, NJ), Trybulski, Eugene John; (Princeton Junction, NJ) Correspondence: Arnold S. Milowsky; 5 Giralda Farms; Madison; NJ; 07940; US Patent Application Number: 20030018026 Date filed: April 10, 2002 Abstract: This invention provides novel substituted tricyclic carboxamides which act as oxytocin receptor competitive antagonists, as well as methods of their manufacture, pharmaceutical compositions and methods of their use in treatment, inhibition,

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suppression or prevention of preterm labor, dysmenorrhea and endometritis, suppression of labor at term prior to caesarean delivery, and to facilitate antinatal transport to a medical facility. These compounds are also useful in enhancing fertility rates, enhancing survival rates and synchronizing estrus in farm animals; and may be useful in the prevention and treatment of disfunctions of the oxytocin system in the central nervous system including obsessive compulsive disorder (OCD) and neuropsychiatric disorders. Excerpt(s): This application claims priority from copending provisional application Serial No. 60/283,261, filed Apr. 12, 2001, the entire disclosure of which is hereby incorporated by reference. This invention concerns novel substituted tricyclic carboxamides which act as oxytocin receptor competitive antagonists, as well as methods of their manufacture, methods of treatment and pharmaceutical compositions utilizing these compounds. The compounds of the present invention are useful therapeutic agents in mammals, particularly in humans. More specifically, they can be used in the treatment and/or prevention and/or suppression of preterm labor and dysmenorrhea, for the suppression of labor at term prior to caesarean delivery, and to facilitate antinatal transport to a medical facility. These compounds are also useful in enhancing fertility rates, enhancing survival rates and synchronizing estrus in farm animals; and may be useful in the prevention and treatment of disfunctions of the oxytocin system in the central nervous system including obsessive compulsive disorder (OCD) and neuropsychiatric disorders. Premature labor remains the leading cause of perinatal mortality and morbidity. Infant mortality dramatically decreases with increased gestational age. The survival rate of prematurely born infants increases from 20% at 24 weeks to 94% at 30 weeks. Moreover the cost associated with the care of an infant born prematurely is extremely high. While many agents have been developed for the treatment of premature labor in the last 40 years, the incidence of pre-term births and low birth weight infants has remained relatively unchanged. Therefore there remains an unmet need for the development of a safe and effective treatment of preterm labor. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Phosphodiesterase type 5 (PDE5) inhibitors for the treatment of selective serotonin reuptake inhibitor (SSR) induced sexual dysfunction Inventor(s): Harrison, Wilma; (Harrison, NY), Siegel, Richard L.; (New York, NY) Correspondence: Gregg C. Benson; Pfizer INC.; Patent Department, MS 4159; Eastern Point Road; Groton; CT; 06340; US Patent Application Number: 20030055070 Date filed: February 19, 2002 Abstract: This invention is directed to the use phosphodiesterase type 5 (PDE5) inhibitors in the treatment of selective serotonin reuptake inhibitor (SSRI) induced sexual dysfunction. Specifically, this invention is directed to a method for treating an animal to cure; prevent or ameliorate SSRI induced sexual dysfunction which comprises administering to the animal an effective amount of the inhibitor. The animal may be a male or a female human. The invention also includes the use of such inhibitors in the manufacture of a medicament to prevent; cure or ameliorate SSRI induced sexual dysfunction. Moreover, the invention includes a kit comprising a SSRI, such as sertraline, fluoxetine, paroxetine, and a PDE5 inhibitor, such as sildenafil citrate, for the treatment or prevention of serotonergic associated disorders such as depression,

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obsessive compulsive disorder or panic disorder, while reducing or preventing sexual dysfunction. Excerpt(s): This application is a continuation of application No. 09/602,790 filed on Jun. 23, 2000, which claims priority from provisional application U.S. serial No. 60/141,980, filed Jul. 1, 1999. This invention relates to the use of phosphodiesterase type 5 (PDE5 ) inhibitors for the treatment of selective serotonin reuptake inhibitor (SSRI) induced sexual dysfunction. In one embodiment the PDE5 inhibitors of this invention are pyrazolopyrimidone compounds, such as pyrazolo[4,3-d]pyrimidin-7-ones, or more specifically sildenafil citrate, VIAGRA.RTM., 1-[[3-(6,7-dihydro-1-methyl-7-oxo-3propyl-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-4-ethoxyphenyl]sulfonyl]-4methylpiperazine citrate. In the general male population, erectile impotence or erectile dysfunction (ED) may be defined as an inability to obtain or sustain an erection adequate for intercourse. Its prevalence is claimed to be between 2 and 7% of the human male population, increasing with age, up to 50 years, and between 18 and 75% between 55 and 80 years of age. In the U.S.A. alone, for example, it has been estimated that there are up to 10 million impotent males, with the majority suffering from problems of organic rather than of psychogenic origin. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Piperidine, tetrahydropyridine and piperazine derivatives, their preparation and use Inventor(s): Bjornholm, Berith; (Vaerlose, DK), Krog-Jensen, Christian; (Kobenhavn O, DK), Moltzen, Ejner Knud; (Gentofte, DK) Correspondence: Darby & Darby P.C.; Post Office Box 5257; New York; NY; 10150-5257; US Patent Application Number: 20020173512 Date filed: May 16, 2002 Abstract: A piperidine, tetrahydropyridine or piperazine derivative having formula (I), 1any of its enantiomers or any mixture thereof, or an acid addition salt thereof, wherein B is C.sub.1-10-alkylene, C.sub.1-10-alkenylene or C.sub.1-10-alkynylene; X is --O--, --S--, or CR.sup.4R.sup.5--; and Y is --CR.sup.6R.sup.7, --CR.sup.6R.sup.7--CR.sup.8R.sup.9, or CR.sup.6.dbd.CR.sup.7--; or X and Y together form a group --CR.sup.4.dbd.CR.sup.5, or --CR.sup.4--CR.sup.5--CR.sup.6R.sup.7-; Z is --O--, or --S--; W is N, C, or CH, and the dotted line is an optional bond; A is a bicyclic ring selected from (Ia) or (Ib) wherein E.sup.1, E.sup.2 and E.sup.3 are selected from O, S, N, NR.sup.11, C, CR.sup.12 and CHR.sup.13, and the dotted line indicates an optional bond, provided that E.sup.2 and E.sup.1 and/or E.sup.3 may not simultaneously be O, or S. The compounds of the invention are considered useful for the treatment of affective disorders, such as depression, psychosis, anxiety disorders including general anxiety disorder, panic disorder, obsessive compulsive disorder, and eating disorders. Excerpt(s): The present invention relates to novel piperidine, tetrahydropyridine and piperazine derivatives which are potent serotonin reuptake inhibitors, pharmaceutical compositions containing these compounds and the use thereof for the treatment of disorders or diseases responsive to the inhibition of serotonin re-uptake. The compounds of the invention also possess antagonistic activity at 5-HT.sub.1A receptors and are considered to be particularly useful for the treatment of depression. Selective serotonin (or 5-HT) reuptake inhibitors (SSRIs) such as fluoxetine, paroxetine, sertraline, fluvoxamine and citalopram represent a major step forward in the treatment of

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depression because they have fewer and less severe side effects compared to first generation antidepressant (tricyclics and non-selective MAO inhibitors). The side effects associated with first generation antidepressants are such that they cause some patients to withdraw from treatment. SSRIs and all other antidepressants currently available suffer from a serious drawback in that several weeks of treatment are necessary to produce the therapeutic effect. The late onset of action is a significant problem, particularly in the treatment of patients with severe depression and suicide potential. Further, one in three patients are not responsive to SSRIs. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

Keeping Current In order to stay informed about patents and patent applications dealing with obsessive compulsive disorder, you can access the U.S. Patent Office archive via the Internet at the following Web address: http://www.uspto.gov/patft/index.html. You will see two broad options: (1) Issued Patent, and (2) Published Applications. To see a list of issued patents, perform the following steps: Under “Issued Patents,” click “Quick Search.” Then, type “obsessive compulsive disorder” (or synonyms) into the “Term 1” box. After clicking on the search button, scroll down to see the various patents which have been granted to date on obsessive compulsive disorder. You can also use this procedure to view pending patent applications concerning obsessive compulsive disorder. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.

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CHAPTER 7. DISORDER

BOOKS

ON

OBSESSIVE

COMPULSIVE

Overview This chapter provides bibliographic book references relating to obsessive compulsive disorder. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on obsessive compulsive disorder include the Combined Health Information Database and the National Library of Medicine. Your local medical library also may have these titles available for loan.

Book Summaries: Federal Agencies The Combined Health Information Database collects various book abstracts from a variety of healthcare institutions and federal agencies. To access these summaries, go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. You will need to use the “Detailed Search” option. To find book summaries, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer. For the format option, select “Monograph/Book.” Now type “obsessive compulsive disorder” (or synonyms) into the “For these words:” box. You should check back periodically with this database which is updated every three months. The following is a typical result when searching for books on obsessive compulsive disorder: •

Tourette Syndrome: The Neurology of a Tic (From the Point of View of the Scientist.) Source: American Speech-Language-Hearing Association. The ASHA Leader, Vol. 7 No. 14, August 6, 2002. Contact: American Speech-Language-Hearing Association. Available from the American Speech-Language-Hearing Association. 10801 Rockville Pike, Rockville, MD 20852. Voice/TTY (800) 498-2071, available 8:30 a.m.-5:00 p.m. ET. E-mail: [email protected]. Web site: http://professional.asha.org/. Summary: The article looks at the pathology of Tourette syndrome (TS) including comorbidities: anxiety disorders, language and learning disorders, mood disorders, attention deficit disorder (ADD), and obsessive compulsive disorders (OCD), vocal and phonic tics, and coprolalia (blurting out obscenities or socially inappropriate words or

132 Obsessive Compulsive Disorder

phrases). The writers also discuss the negative impact that these symptoms can have on an individual with TS, in childhood and adult life, and appropriate speech treatment for TS. Selected references are included at the end of the article. This is a two-part article. (See also The Anatomy of a Tic--From the Point of View of a Person With TS.) Selected references. •

Children With Tourette Syndrome: A Parents' Guide Source: Rockville, MD: Woodbine House, Inc. 1992. 350 p. Contact: Available from Woodbine House, Inc. 5615 Fishers Lane, Rockville, MD 20852. (800) 843-7323. PRICE: $14.95 plus shipping and handling. ISBN: 0933149441. Summary: This handbook, written for parents of children and teenagers with Tourette Syndrome, offers up-to-date, concrete information and advice for dealing with this neurological disorder. The authors offer families a foundation for understanding this complex disorder and for developing strategies that can help their child become a productive, happy adult. Topics covered include medical, educational, legal, family life, daily care, and emotional issues. The authors discuss treatments, including those for related conditions such as attention deficit disorder (ADD) and obsessive compulsive disorder (OCD); behavior management techniques; tips on handling the reactions of others; parent advocacy; coping with feelings of guilt and resentment; and getting help for a child at school. Coprolalia and language development are also discussed. Tables listing developmental milestones in language and other areas are included. Parent statements appear at the end of each chapter; experienced parents share feelings and practical insights that can be especially helpful to new parents. The book concludes with a detailed listing of organizations (including state-by-state resources), a reading list, a subject index, and a glossary. (AA-M).

Book Summaries: Online Booksellers Commercial Internet-based booksellers, such as Amazon.com and Barnes&Noble.com, offer summaries which have been supplied by each title’s publisher. Some summaries also include customer reviews. Your local bookseller may have access to in-house and commercial databases that index all published books (e.g. Books in Print). IMPORTANT NOTE: Online booksellers typically produce search results for medical and non-medical books. When searching for “obsessive compulsive disorder” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “obsessive compulsive disorder” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “obsessive compulsive disorder” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •

…nine, ten do it again. A Guide to Obsessive Compulsive Disorder. For people with OCD & their families by Kathryn I'Anson; ISBN: 0646308076; http://www.amazon.com/exec/obidos/ASIN/0646308076/icongroupinterna

•

A Thousand Frightening Fantasies: Understanding and Healing Scrupulosity and Obsessive Compulsive Disorder by William Van Ornum; ISBN: 0824516052; http://www.amazon.com/exec/obidos/ASIN/0824516052/icongroupinterna

•

Anxiety Disorders Comorbid with Depression - Volume 2: Social Phobia, Generalized Anxiety Disorder, Obsessive Compulsive Disorder and Post Traumatic Stress Disorder - Pocketbook by Dan J. Stein, Eric Hollander; ISBN: 1841840505; http://www.amazon.com/exec/obidos/ASIN/1841840505/icongroupinterna

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•

Childhood Obsessive Compulsive Disorder by Greta Francis (Author), Rod A. Gragg (Author) (1996); ISBN: 0803959222; http://www.amazon.com/exec/obidos/ASIN/0803959222/icongroupinterna

•

Children With Obsessive Compulsive Disorder (Changing Behavior Through Understanding Series) by Siegel (1991); ISBN: 1564560473; http://www.amazon.com/exec/obidos/ASIN/1564560473/icongroupinterna

•

Curing Anxiety, Phobias, Shyness and Obsessive Compulsive Disorders by Howard Liebgold, Kaiser Graphics (Illustrator); ISBN: 1931487006; http://www.amazon.com/exec/obidos/ASIN/1931487006/icongroupinterna

•

Current Insights in Obsessive Compulsive Disorder by Eric Hollander (Editor), et al; ISBN: 0471951420; http://www.amazon.com/exec/obidos/ASIN/0471951420/icongroupinterna

•

Everything in Its Place: My Trials and Triumphs With Obsessive Compulsive Disorder by Marc Summers, Eric Hollander (Contributor) (2000); ISBN: 1585420484; http://www.amazon.com/exec/obidos/ASIN/1585420484/icongroupinterna

•

From Thoughts to Obsessions: Obsessive Compulsive Disorder in Children and Adolescents by Per Hove Thomsen (1999); ISBN: 1853027219; http://www.amazon.com/exec/obidos/ASIN/1853027219/icongroupinterna

•

Mastery of Obsessive Compulsive Disorder: Therapist Guide (Therapyworks Series) by Michael J. Kozak, Edna B. Foa; ISBN: 0158131649; http://www.amazon.com/exec/obidos/ASIN/0158131649/icongroupinterna

•

Obsessional Thoughts and Behaviour: Help for Obsessive Compulsive Disorder by Frederick Dr. Toates; ISBN: 0722521952; http://www.amazon.com/exec/obidos/ASIN/0722521952/icongroupinterna

•

Obsessive Compulsive Anonymous: Recovering from Obsessive Compulsive Disorder by Obsessive Compulsive Anonymous World Ser (1999); ISBN: 0962806625; http://www.amazon.com/exec/obidos/ASIN/0962806625/icongroupinterna

•

Obsessive Compulsive Anonymous: Recovering from Obsessive Compulsive Disorder by Compulsive Anonymous Obsessive; ISBN: 0962806609; http://www.amazon.com/exec/obidos/ASIN/0962806609/icongroupinterna

•

Obsessive Compulsive Disorder by Bruce M. Hyman (Author), Cherry Pedrick (Author); ISBN: 0761327584; http://www.amazon.com/exec/obidos/ASIN/0761327584/icongroupinterna

•

Obsessive Compulsive Disorder - pocketbook by Stuart Montgomery, Joseph Zohar; ISBN: 1853173878; http://www.amazon.com/exec/obidos/ASIN/1853173878/icongroupinterna

•

Obsessive Compulsive Disorder in Children and Adolescents: A Guide by Hugh F. Johnston, J. Jay Fruehling; ISBN: 189080228X; http://www.amazon.com/exec/obidos/ASIN/189080228X/icongroupinterna

•

Obsessive Compulsive Disorder: A Cognitive and Neuropsychological Perspective (Wiley Series in Clinical Psychology) by Frank Tallis; ISBN: 0471957755; http://www.amazon.com/exec/obidos/ASIN/0471957755/icongroupinterna

•

Obsessive Compulsive Disorder: A Guide by John H. Greist; ISBN: 1890802034; http://www.amazon.com/exec/obidos/ASIN/1890802034/icongroupinterna

134 Obsessive Compulsive Disorder

•

Obsessive Compulsive Disorder: A Survival Guide for Family and Friends by Roy C., et al (1997); ISBN: 0962806617; http://www.amazon.com/exec/obidos/ASIN/0962806617/icongroupinterna

•

Obsessive Compulsive Disorder: New Help for the Family by Herbert L. Gravitz (1998); ISBN: 0966110447; http://www.amazon.com/exec/obidos/ASIN/0966110447/icongroupinterna

•

Obsessive Compulsive Disorder: The Latest Assessment and Treatment Strategies by Gail Steketee (Editor), et al; ISBN: 188753718X; http://www.amazon.com/exec/obidos/ASIN/188753718X/icongroupinterna

•

Obsessive Compulsive Disorder: What It Is - How to Deal with It by Frederick Toates; ISBN: 0722529120; http://www.amazon.com/exec/obidos/ASIN/0722529120/icongroupinterna

•

Obsessive Compulsive Disorders: a practical guide by Naomi Fineberg, et al (2001); ISBN: 1853179191; http://www.amazon.com/exec/obidos/ASIN/1853179191/icongroupinterna

•

Ocd Casebook: Obsessive Compulsive Disorder by John H. Greist (Editor), et al (1995); ISBN: 0880487291; http://www.amazon.com/exec/obidos/ASIN/0880487291/icongroupinterna

•

Regaining self-control : conquering obsessive compulsive behavior and other habits you want to break by A. John Bennee; ISBN: 1555171028; http://www.amazon.com/exec/obidos/ASIN/1555171028/icongroupinterna

•

The Boy Who Couldn't Stop Washing: The Experience and Treatment of Obsessive Compulsive Disorder by Judith L. Rapoport; ISBN: 0451172027; http://www.amazon.com/exec/obidos/ASIN/0451172027/icongroupinterna

•

The Treatment of Phobic and Obsessive Compulsive Disorders: Selected Papers from the Sixth Annual Meeting of the European Association of Behavior the by John C. and Rabalivas, Andreas D. Boulougouris (Editor); ISBN: 008021472X; http://www.amazon.com/exec/obidos/ASIN/008021472X/icongroupinterna

•

Tictionary: A Reference Guide to the World of Tourette Syndrome, Asperger Syndrome, Attention Deficit Hyperactivity Disorder and Obsessive Compulsive Disorder for Parents and Professionals by Becky Ottinger, Fred Engh; ISBN: 1931282161; http://www.amazon.com/exec/obidos/ASIN/1931282161/icongroupinterna

•

Tormenting Thoughts and Secret Rituals: The Hidden Epidemic of Obsessive Compulsive Disorder by Ian Osborn (1999); ISBN: 0440508479; http://www.amazon.com/exec/obidos/ASIN/0440508479/icongroupinterna

•

Treatment of Obsessive Compulsive Disorder by Gail S. Steketee, Andrew W. Ellis; ISBN: 089862911X; http://www.amazon.com/exec/obidos/ASIN/089862911X/icongroupinterna

•

Understanding Tourette Syndrome, Obsessive Compulsive Disorder and Related Problems: A Developmental and Catastrophe Theory Perspective by John Michael Berecz, Gary Larson (Illustrator); ISBN: 082617390X; http://www.amazon.com/exec/obidos/ASIN/082617390X/icongroupinterna

Books

135

The National Library of Medicine Book Index The National Library of Medicine at the National Institutes of Health has a massive database of books published on healthcare and biomedicine. Go to the following Internet site, http://locatorplus.gov/, and then select “Search LOCATORplus.” Once you are in the search area, simply type “obsessive compulsive disorder” (or synonyms) into the search box, and select “books only.” From there, results can be sorted by publication date, author, or relevance. The following was recently catalogued by the National Library of Medicine:11 •

The basal-cortical function in obsessive compulsive disorder spectrum Author: Bellodi, Laura.; Year: 1972; Pisa: Pacini, c2000; ISBN: 8877813954

Chapters on Obsessive Compulsive Disorder In order to find chapters that specifically relate to obsessive compulsive disorder, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and obsessive compulsive disorder using the “Detailed Search” option. Go to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find book chapters, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Book Chapter.” Type “obsessive compulsive disorder” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on obsessive compulsive disorder: •

Chronic Tinnitus Following Electroconvulsive Therapy Source: in Hazell, J., ed. Proceedings of the Sixth International Tinnitus Seminar. London, England: Tinnitus and Hyperacusis Centre. 1999. p. 243-245. Contact: Available from Tinnitus and Hyperacusis Centre. 32 Devonshire Place, London, W1N 1PE, United Kingdom. Fax 44 + (0) 207 486 2218. E-mail: [email protected]. Website: www.tinnitus.org. PRICE: Contact publisher for price. ISBN: 0953695700. Also available on CD-ROM. Summary: Tinnitus can be caused by almost any pathology involving the auditory system and can also result from head trauma, a variety of medications, and electrical shock, including lightning strikes. This article is from a lengthy document that reprints the proceedings of the Sixth International Tinnitus Seminar, held in Cambridge, United Kingdom, in September 1999 and hosted by the British Society of Audiology. In this article, the authors report a case study of chronic tinnitus that began immediately following electroconvulsive therapy (ECT). A 43 year old female with a 27 year history of obsessive compulsive disorder and major depression had previously been treated with psychotherapy, antidepressant and antipsychotic medications. Because these treatments were minimally effective and because the frequency and duration of her

11

In addition to LOCATORPlus, in collaboration with authors and publishers, the National Center for Biotechnology Information (NCBI) is currently adapting biomedical books for the Web. The books may be accessed in two ways: (1) by searching directly using any search term or phrase (in the same way as the bibliographic database PubMed), or (2) by following the links to PubMed abstracts. Each PubMed abstract has a "Books" button that displays a facsimile of the abstract in which some phrases are hypertext links. These phrases are also found in the books available at NCBI. Click on hyperlinked results in the list of books in which the phrase is found. Currently, the majority of the links are between the books and PubMed. In the future, more links will be created between the books and other types of information, such as gene and protein sequences and macromolecular structures. See http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Books.

136 Obsessive Compulsive Disorder

depressive episodes continued to increase, the patient was scheduled to undergo a series of ECT procedures. The patient received four ECT treatments during one week. Stimulating current was delivered through a unilateral electrode to the right frontotemporal region of the head. EEG seizures occurred during each of the ECT procedures. After the patient recovered from anesthesia, she complained of headaches, muscle pain, amnesia, and, after the fourth ECT, she reported a ringing sound in her right ear. Audiometric testing the day after the fourth ECT revealed a slight increase in threshold for 8000 Hz tones in her right ear. The authors conclude that it is likely that current delivered during the fourth ECT treatment triggered the perception of tinnitus for this patient. The unique organization of this patient's central nervous and auditory systems combined with her particular pharmacological history might have predisposed her to developing this symptom.

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CHAPTER 8. MULTIMEDIA ON OBSESSIVE COMPULSIVE DISORDER Overview In this chapter, we show you how to keep current on multimedia sources of information on obsessive compulsive disorder. We start with sources that have been summarized by federal agencies, and then show you how to find bibliographic information catalogued by the National Library of Medicine.

Bibliography: Multimedia on Obsessive Compulsive Disorder The National Library of Medicine is a rich source of information on healthcare-related multimedia productions including slides, computer software, and databases. To access the multimedia database, go to the following Web site: http://locatorplus.gov/. Select “Search LOCATORplus.” Once in the search area, simply type in obsessive compulsive disorder (or synonyms). Then, in the option box provided below the search box, select “Audiovisuals and Computer Files.” From there, you can choose to sort results by publication date, author, or relevance. The following multimedia has been indexed on obsessive compulsive disorder: •

Diagnosis and treatment of childhood obsessive compulsive disorders [videorecording] Source: produced by the Department of Psychiatry and Behavioral Sciences and the Health Communications Network; Year: 1990; Format: Videorecording; Charleston, S.C.: Medical University of South Carolina, c1990

•

Etiology, symptomatology, and treatment of obsessive compulsive disorder [videorecording] Source: [presented by] Marshfield Clinic. [et al.]; Year: 1991; Format: Videorecording; Marshfield, WI: Marshfield Video Network, [1991]

•

Obsessive compulsive disorder [videorecording] Source: [presented by] Marshfield Clinic, Saint Joseph's Hospital [and] Marshfield Medical Research Foundation; Year: 1990; Format: Videorecording; Marshfield, WI: Marshfield Video Network, [1990]

•

Obsessive compulsive disorder [videorecording] Source: a presentation of Films for the Humanities & Sciences; Dark Horse Productions Limited production for BBC; Year: 1997; Format: Videorecording; Princeton, N.J.: Films for the Humanities & Sciences, c1997

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•

Psychiatric challenges for the primary care physician [videorecording]: obsessive compulsive disorder Source: faculty, John H. Griest; editor-in-chief, Jerrold F. Rosenbaum; host/advisor, James G. Jones; Year: 1996; Format: Videorecording; Secaucus, N.J.: Network for Continuing Medical Education, c1996

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CHAPTER 9. PERIODICALS AND NEWS ON OBSESSIVE COMPULSIVE DISORDER Overview In this chapter, we suggest a number of news sources and present various periodicals that cover obsessive compulsive disorder.

News Services and Press Releases One of the simplest ways of tracking press releases on obsessive compulsive disorder is to search the news wires. In the following sample of sources, we will briefly describe how to access each service. These services only post recent news intended for public viewing. PR Newswire To access the PR Newswire archive, simply go to http://www.prnewswire.com/. Select your country. Type “obsessive compulsive disorder” (or synonyms) into the search box. You will automatically receive information on relevant news releases posted within the last 30 days. The search results are shown by order of relevance. Reuters Health The Reuters’ Medical News and Health eLine databases can be very useful in exploring news archives relating to obsessive compulsive disorder. While some of the listed articles are free to view, others are available for purchase for a nominal fee. To access this archive, go to http://www.reutershealth.com/en/index.html and search by “obsessive compulsive disorder” (or synonyms). The following was recently listed in this archive for obsessive compulsive disorder: •

Eon Labs wins FDA approval to sell generic Luvox for obsessive compulsive disorder Source: Reuters Industry Breifing Date: December 15, 2000

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The NIH Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within its search engine. Business Wire Business Wire is similar to PR Newswire. To access this archive, simply go to http://www.businesswire.com/. You can scan the news by industry category or company name. Market Wire Market Wire is more focused on technology than the other wires. To browse the latest press releases by topic, such as alternative medicine, biotechnology, fitness, healthcare, legal, nutrition, and pharmaceuticals, access Market Wire’s Medical/Health channel at http://www.marketwire.com/mw/release_index?channel=MedicalHealth. Or simply go to Market Wire’s home page at http://www.marketwire.com/mw/home, type “obsessive compulsive disorder” (or synonyms) into the search box, and click on “Search News.” As this service is technology oriented, you may wish to use it when searching for press releases covering diagnostic procedures or tests. Search Engines Medical news is also available in the news sections of commercial Internet search engines. See the health news page at Yahoo (http://dir.yahoo.com/Health/News_and_Media/), or you can use this Web site’s general news search page at http://news.yahoo.com/. Type in “obsessive compulsive disorder” (or synonyms). If you know the name of a company that is relevant to obsessive compulsive disorder, you can go to any stock trading Web site (such as http://www.etrade.com/) and search for the company name there. News items across various news sources are reported on indicated hyperlinks. Google offers a similar service at http://news.google.com/. BBC Covering news from a more European perspective, the British Broadcasting Corporation (BBC) allows the public free access to their news archive located at http://www.bbc.co.uk/. Search by “obsessive compulsive disorder” (or synonyms).

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Newsletter Articles Use the Combined Health Information Database, and limit your search criteria to “newsletter articles.” Again, you will need to use the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. Go to the bottom of the search page where “You may refine your search by.” Select the dates and language that you prefer. For the format option, select “Newsletter Article.” Type “obsessive compulsive disorder” (or synonyms) into the “For these words:” box. You should check back periodically with this database as it is updated every three months. The following is a typical result when searching for newsletter articles on obsessive compulsive disorder: •

Obsessive Compulsive Disorder and Eating Disorders Source: American Anorexia/Bulimia Association Newsletter. p.4-5. Summer 1998. Contact: American Anorexia/Bulimia Association, 165 West 46 Street, Suite 1108, New York, NY 10036. (212) 575- 6200. Summary: Wall argues that many eating-disordered patients are obsessive-compulsive disordered (OCD), and food is the medium of their obsession-compulsion. He notes that most eating-disordered patients are women, and that women are conditioned by society to worry more about food and their weight than men. Therefore, says Wall, an eating disorder is the form taken by the patient's OCD. He suggests that eating disorders could be treated by many of the same methods used for OCD, such as anti- depressant medications and response prevention therapy.

Academic Periodicals covering Obsessive Compulsive Disorder Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to obsessive compulsive disorder. In addition to these sources, you can search for articles covering obsessive compulsive disorder that have been published by any of the periodicals listed in previous chapters. To find the latest studies published, go to http://www.ncbi.nlm.nih.gov/pubmed, type the name of the periodical into the search box, and click “Go.” If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”

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CHAPTER 10. RESEARCHING MEDICATIONS Overview While a number of hard copy or CD-ROM resources are available for researching medications, a more flexible method is to use Internet-based databases. Broadly speaking, there are two sources of information on approved medications: public sources and private sources. We will emphasize free-to-use public sources.

U.S. Pharmacopeia Because of historical investments by various organizations and the emergence of the Internet, it has become rather simple to learn about the medications recommended for obsessive compulsive disorder. One such source is the United States Pharmacopeia. In 1820, eleven physicians met in Washington, D.C. to establish the first compendium of standard drugs for the United States. They called this compendium the U.S. Pharmacopeia (USP). Today, the USP is a non-profit organization consisting of 800 volunteer scientists, eleven elected officials, and 400 representatives of state associations and colleges of medicine and pharmacy. The USP is located in Rockville, Maryland, and its home page is located at http://www.usp.org/. The USP currently provides standards for over 3,700 medications. The resulting USP DI Advice for the Patient can be accessed through the National Library of Medicine of the National Institutes of Health. The database is partially derived from lists of federally approved medications in the Food and Drug Administration’s (FDA) Drug Approvals database, located at http://www.fda.gov/cder/da/da.htm. While the FDA database is rather large and difficult to navigate, the Phamacopeia is both user-friendly and free to use. It covers more than 9,000 prescription and over-the-counter medications. To access this database, simply type the following hyperlink into your Web browser: http://www.nlm.nih.gov/medlineplus/druginformation.html. To view examples of a given medication (brand names, category, description, preparation, proper use, precautions, side effects, etc.), simply follow the hyperlinks indicated within the United States Pharmacopeia (USP). Below, we have compiled a list of medications associated with obsessive compulsive disorder. If you would like more information on a particular medication, the provided hyperlinks will direct you to ample documentation (e.g. typical dosage, side effects, drug-

144 Obsessive Compulsive Disorder

interaction risks, etc.). The following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to obsessive compulsive disorder: Fluoxetine •

Systemic - U.S. Brands: Prozac; Sarafem http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202247.html

Commercial Databases In addition to the medications listed in the USP above, a number of commercial sites are available by subscription to physicians and their institutions. Or, you may be able to access these sources from your local medical library.

Mosby’s Drug Consult Mosby’s Drug Consult database (also available on CD-ROM and book format) covers 45,000 drug products including generics and international brands. It provides prescribing information, drug interactions, and patient information. Subscription information is available at the following hyperlink: http://www.mosbysdrugconsult.com/. PDRhealth The PDRhealth database is a free-to-use, drug information search engine that has been written for the public in layman’s terms. It contains FDA-approved drug information adapted from the Physicians’ Desk Reference (PDR) database. PDRhealth can be searched by brand name, generic name, or indication. It features multiple drug interactions reports. Search PDRhealth at http://www.pdrhealth.com/drug_info/index.html. Other Web Sites Drugs.com (www.drugs.com) reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. (http://www.medletter.com/) which allows users to download articles on various drugs and therapeutics for a nominal fee. If you have any questions about a medical treatment, the FDA may have an office near you. Look for their number in the blue pages of the phone book. You can also contact the FDA through its toll-free number, 1-888-INFO-FDA (1-888-463-6332), or on the World Wide Web at www.fda.gov.

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APPENDICES

147

APPENDIX A. PHYSICIAN RESOURCES Overview In this chapter, we focus on databases and Internet-based guidelines and information resources created or written for a professional audience.

NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute12: •

Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm

•

National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/

•

National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html

•

National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25

•

National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm

•

National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm

•

National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375

•

National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/

12

These publications are typically written by one or more of the various NIH Institutes.

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•

National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm

•

National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/

•

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm

•

National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm

•

National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/

•

National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/

•

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm

•

National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html

•

National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm

•

National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm

•

National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm

•

National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html

•

National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm

•

Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp

•

National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/

•

National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp

•

Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html

•

Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm

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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.13 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:14 •

Bioethics: Access to published literature on the ethical, legal, and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html

•

HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html

•

NLM Online Exhibitions: Describes “Exhibitions in the History of Medicine”: http://www.nlm.nih.gov/exhibition/exhibition.html. Additional resources for historical scholarship in medicine: http://www.nlm.nih.gov/hmd/hmd.html

•

Biotechnology Information: Access to public databases. The National Center for Biotechnology Information conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease: http://www.ncbi.nlm.nih.gov/

•

Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html

•

Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html

•

Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/

•

Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html

•

Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html

•

Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html

•

MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html

13 Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 14 See http://www.nlm.nih.gov/databases/databases.html.

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•

Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html

•

Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html

The NLM Gateway15 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.16 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “obsessive compulsive disorder” (or synonyms) into the search box and click “Search.” The results will be presented in a tabular form, indicating the number of references in each database category. Results Summary Category Journal Articles Books / Periodicals / Audio Visual Consumer Health Meeting Abstracts Other Collections Total

Items Found 6342 196 575 3 5 7121

HSTAT17 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.18 These documents include clinical practice guidelines, quickreference guides for clinicians, consumer health brochures, evidence reports and technology assessments from the Agency for Healthcare Research and Quality (AHRQ), as well as AHRQ’s Put Prevention Into Practice.19 Simply search by “obsessive compulsive disorder” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

15

Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.

16

The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH). 17 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 18 19

The HSTAT URL is http://hstat.nlm.nih.gov/.

Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention (SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force's Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services’ Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations.

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Coffee Break: Tutorials for Biologists20 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.21 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.22 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.

Other Commercial Databases In addition to resources maintained by official agencies, other databases exist that are commercial ventures addressing medical professionals. Here are some examples that may interest you: •

CliniWeb International: Index and table of contents to selected clinical information on the Internet; see http://www.ohsu.edu/cliniweb/.

•

Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.

The Genome Project and Obsessive Compulsive Disorder In the following section, we will discuss databases and references which relate to the Genome Project and obsessive compulsive disorder. Online Mendelian Inheritance in Man (OMIM) The Online Mendelian Inheritance in Man (OMIM) database is a catalog of human genes and genetic disorders authored and edited by Dr. Victor A. McKusick and his colleagues at Johns Hopkins and elsewhere. OMIM was developed for the World Wide Web by the National Center for Biotechnology Information (NCBI).23 The database contains textual information, pictures, and reference information. It also contains copious links to NCBI’s Entrez database of MEDLINE articles and sequence information.

20 Adapted 21

from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html.

The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 22 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process. 23 Adapted from http://www.ncbi.nlm.nih.gov/. Established in 1988 as a national resource for molecular biology information, NCBI creates public databases, conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information--all for the better understanding of molecular processes affecting human health and disease.

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To search the database, go to http://www.ncbi.nlm.nih.gov/Omim/searchomim.html. Type “obsessive compulsive disorder” (or synonyms) into the search box, and click “Submit Search.” If too many results appear, you can narrow the search by adding the word “clinical.” Each report will have additional links to related research and databases. In particular, the option “Database Links” will search across technical databases that offer an abundance of information. The following is an example of the results you can obtain from the OMIM for obsessive compulsive disorder: •

Obsessive-Compulsive Disorder 1; OCD1 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?164230 Genes and Disease (NCBI - Map)

The Genes and Disease database is produced by the National Center for Biotechnology Information of the National Library of Medicine at the National Institutes of Health. This Web site categorizes each disorder by system of the body. Go to http://www.ncbi.nlm.nih.gov/disease/, and browse the system pages to have a full view of important conditions linked to human genes. Since this site is regularly updated, you may wish to revisit it from time to time. The following systems and associated disorders are addressed: •

Cancer: Uncontrolled cell division. Examples: Breast and ovarian cancer, Burkitt lymphoma, chronic myeloid leukemia, colon cancer, lung cancer, malignant melanoma, multiple endocrine neoplasia, neurofibromatosis, p53 tumor suppressor, pancreatic cancer, prostate cancer, Ras oncogene, RB: retinoblastoma, von Hippel-Lindau syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Cancer.html

•

Immune System: Fights invaders. Examples: Asthma, autoimmune polyglandular syndrome, Crohn’s disease, DiGeorge syndrome, familial Mediterranean fever, immunodeficiency with Hyper-IgM, severe combined immunodeficiency. Web site: http://www.ncbi.nlm.nih.gov/disease/Immune.html

•

Metabolism: Food and energy. Examples: Adreno-leukodystrophy, atherosclerosis, Best disease, Gaucher disease, glucose galactose malabsorption, gyrate atrophy, juvenile-onset diabetes, obesity, paroxysmal nocturnal hemoglobinuria, phenylketonuria, Refsum disease, Tangier disease, Tay-Sachs disease. Web site: http://www.ncbi.nlm.nih.gov/disease/Metabolism.html

•

Muscle and Bone: Movement and growth. Examples: Duchenne muscular dystrophy, Ellis-van Creveld syndrome, Marfan syndrome, myotonic dystrophy, spinal muscular atrophy. Web site: http://www.ncbi.nlm.nih.gov/disease/Muscle.html

•

Nervous System: Mind and body. Examples: Alzheimer disease, amyotrophic lateral sclerosis, Angelman syndrome, Charcot-Marie-Tooth disease, epilepsy, essential tremor, fragile X syndrome, Friedreich’s ataxia, Huntington disease, Niemann-Pick disease, Parkinson disease, Prader-Willi syndrome, Rett syndrome, spinocerebellar atrophy, Williams syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Brain.html

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•

Signals: Cellular messages. Examples: Ataxia telangiectasia, Cockayne syndrome, glaucoma, male-patterned baldness, SRY: sex determination, tuberous sclerosis, Waardenburg syndrome, Werner syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Signals.html

•

Transporters: Pumps and channels. Examples: Cystic fibrosis, deafness, diastrophic dysplasia, Hemophilia A, long-QT syndrome, Menkes syndrome, Pendred syndrome, polycystic kidney disease, sickle cell anemia, Wilson’s disease, Zellweger syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Transporters.html Entrez

Entrez is a search and retrieval system that integrates several linked databases at the National Center for Biotechnology Information (NCBI). These databases include nucleotide sequences, protein sequences, macromolecular structures, whole genomes, and MEDLINE through PubMed. Entrez provides access to the following databases: •

3D Domains: Domains from Entrez Structure, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo

•

Books: Online books, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=books

•

Genome: Complete genome assemblies, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Genome

•

NCBI’s Protein Sequence Information Survey Results: Web site: http://www.ncbi.nlm.nih.gov/About/proteinsurvey/

•

Nucleotide Sequence Database (Genbank): Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Nucleotide

•

OMIM: Online Mendelian Inheritance in Man, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM

•

PopSet: Population study data sets, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Popset

•

ProbeSet: Gene Expression Omnibus (GEO), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo

•

Protein Sequence Database: Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Protein

•

PubMed: Biomedical literature (PubMed), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed

•

Structure: Three-dimensional macromolecular structures, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Structure

•

Taxonomy: Organisms in GenBank, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Taxonomy

To access the Entrez system at the National Center for Biotechnology Information, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=genome, and then

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select the database that you would like to search. The databases available are listed in the drop box next to “Search.” Enter “obsessive compulsive disorder” (or synonyms) into the search box and click “Go.” Jablonski’s Multiple Congenital Anomaly/Mental Retardation (MCA/MR) Syndromes Database24 This online resource has been developed to facilitate the identification and differentiation of syndromic entities. Special attention is given to the type of information that is usually limited or completely omitted in existing reference sources due to space limitations of the printed form. At http://www.nlm.nih.gov/mesh/jablonski/syndrome_toc/toc_a.html, you can search across syndromes using an alphabetical index. Search by keywords at http://www.nlm.nih.gov/mesh/jablonski/syndrome_db.html. The Genome Database25 Established at Johns Hopkins University in Baltimore, Maryland in 1990, the Genome Database (GDB) is the official central repository for genomic mapping data resulting from the Human Genome Initiative. In the spring of 1999, the Bioinformatics Supercomputing Centre (BiSC) at the Hospital for Sick Children in Toronto, Ontario assumed the management of GDB. The Human Genome Initiative is a worldwide research effort focusing on structural analysis of human DNA to determine the location and sequence of the estimated 100,000 human genes. In support of this project, GDB stores and curates data generated by researchers worldwide who are engaged in the mapping effort of the Human Genome Project (HGP). GDB’s mission is to provide scientists with an encyclopedia of the human genome which is continually revised and updated to reflect the current state of scientific knowledge. Although GDB has historically focused on gene mapping, its focus will broaden as the Genome Project moves from mapping to sequence, and finally, to functional analysis. To access the GDB, simply go to the following hyperlink: http://www.gdb.org/. Search “All Biological Data” by “Keyword.” Type “obsessive compulsive disorder” (or synonyms) into the search box, and review the results. If more than one word is used in the search box, then separate each one with the word “and” or “or” (using “or” might be useful when using synonyms).

24 Adapted from the National Library of Medicine: http://www.nlm.nih.gov/mesh/jablonski/about_syndrome.html. 25 Adapted from the Genome Database: http://gdbwww.gdb.org/gdb/aboutGDB.html - mission.

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APPENDIX B. PATIENT RESOURCES Overview Official agencies, as well as federally funded institutions supported by national grants, frequently publish a variety of guidelines written with the patient in mind. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. Since new guidelines on obsessive compulsive disorder can appear at any moment and be published by a number of sources, the best approach to finding guidelines is to systematically scan the Internet-based services that post them.

Patient Guideline Sources The remainder of this chapter directs you to sources which either publish or can help you find additional guidelines on topics related to obsessive compulsive disorder. Due to space limitations, these sources are listed in a concise manner. Do not hesitate to consult the following sources by either using the Internet hyperlink provided, or, in cases where the contact information is provided, contacting the publisher or author directly. The National Institutes of Health The NIH gateway to patients is located at http://health.nih.gov/. From this site, you can search across various sources and institutes, a number of which are summarized below. Topic Pages: MEDLINEplus The National Library of Medicine has created a vast and patient-oriented healthcare information portal called MEDLINEplus. Within this Internet-based system are “health topic pages” which list links to available materials relevant to obsessive compulsive disorder. To access this system, log on to http://www.nlm.nih.gov/medlineplus/healthtopics.html. From there you can either search using the alphabetical index or browse by broad topic areas. Recently, MEDLINEplus listed the following when searched for “obsessive compulsive disorder”:

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•

Guides on obsessive compulsive disorder Obsessive-Compulsive Disorder http://www.nlm.nih.gov/medlineplus/obsessivecompulsivedisorder.html

•

Other guides Eating Disorders http://www.nlm.nih.gov/medlineplus/eatingdisorders.html Teen Mental Health http://www.nlm.nih.gov/medlineplus/teenmentalhealth.html Tourette Syndrome http://www.nlm.nih.gov/medlineplus/tourettesyndrome.html

You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the exception that it only includes materials that are linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search. Healthfinder™ Healthfinder™ is sponsored by the U.S. Department of Health and Human Services and offers links to hundreds of other sites that contain healthcare information. This Web site is located at http://www.healthfinder.gov. Again, keyword searches can be used to find guidelines. The following was recently found in this database: •

Obsessive Compulsive Disorder (OCD): A Real Illness Source: National Institute of Mental Health, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6564 The NIH Search Utility

The NIH search utility allows you to search for documents on over 100 selected Web sites that comprise the NIH-WEB-SPACE. Each of these servers is “crawled” and indexed on an ongoing basis. Your search will produce a list of various documents, all of which will relate in some way to obsessive compulsive disorder. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html.

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Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •

AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats

•

Family Village: http://www.familyvillage.wisc.edu/specific.htm

•

Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/

•

Med Help International: http://www.medhelp.org/HealthTopics/A.html

•

Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/

•

Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/

•

WebMDHealth: http://my.webmd.com/health_topics

Associations and Obsessive Compulsive Disorder The following is a list of associations that provide information on and resources relating to obsessive compulsive disorder: •

Lithium Information Center/Obsessive Compulsive Information Center Telephone: (608) 827-2470 Fax: (608) 827-2479 Email: [email protected] Web Site: http://www.miminc.org Background: The Lithium Information Center and Obsessive Compulsive Information Center are affiliated with the Madison Institute of Medicine, a not-for-profit organization committed to conceptualizing, developing, and disseminating innovative approaches to the education of professionals, consumers, and the general public about psychiatric disorders and their treatment. An additional focus of the Institute is clinical research as a vehicle to advance the frontiers of medicine and improve quality of life. At the core of the Institute's educational efforts are the Lithium Information Center (LIC) and the Obsessive Compulsive Information Center (OCIC). The LIC acquires, catalogs, and disseminates information on the biomedical uses of lithium and other medications for the treatment of bipolar (manic-depressive) disorder, a psychiatric disorder in which affected individuals experience recurrent mood swings including episodes of depression and episodes characterized by overactivity, elation, irritability, and other symptoms (mania). The Center currently has more than 28,000 references on such topic areas as lithium treatment in bipolar disorder or related psychiatric disorders, use of lithium during pregnancy, interactions with other medications, and appropriate monitoring procedures. The Obsessive Compulsive Center obtains, catalogs, and distributes biomedical information concerning obsessive compulsive disorder (OCD) and related disorders. OCD is an anxiety disorder characterized by repetitive actions or rituals (compulsions) performed in response to recurrent obsessive thoughts, according to certain rules. The OCIC currently has more than 12,000 references on file on such topics as OCD, related disorders including trichotillomania and body dysmorphic disorder, diagnosis and classification, behavior therapy, and pharmacologic therapy. The LIC's and OCIC's references include medical journal articles, books, book chapters,

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government documents, meeting proceedings, pamphlets, magazine articles, and other documents. Reference files may be searched by author, title word, key word (subject), publication name, and year of publication. In response to requests, the Centers provide computer-printed bibliographies and single photocopies of articles (subject to copyright law) on any topic relating to lithium or OCD. The Centers also maintain physician and support group referral lists. The Madison Institute of Medicine also hosts semiannual Continuing Medical Education (CME) conferences concerning mental health and health care issues. Such programs are endorsed and certified by the University of Wisconsin Medical School Continuing Medical Education.

Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to obsessive compulsive disorder. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with obsessive compulsive disorder. The National Health Information Center (NHIC) The National Health Information Center (NHIC) offers a free referral service to help people find organizations that provide information about obsessive compulsive disorder. For more information, see the NHIC’s Web site at http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797. Directory of Health Organizations The Directory of Health Organizations, provided by the National Library of Medicine Specialized Information Services, is a comprehensive source of information on associations. The Directory of Health Organizations database can be accessed via the Internet at http://www.sis.nlm.nih.gov/Dir/DirMain.html. It is composed of two parts: DIRLINE and Health Hotlines. The DIRLINE database comprises some 10,000 records of organizations, research centers, and government institutes and associations that primarily focus on health and biomedicine. To access DIRLINE directly, go to the following Web site: http://dirline.nlm.nih.gov/. Simply type in “obsessive compulsive disorder” (or a synonym), and you will receive information on all relevant organizations listed in the database. Health Hotlines directs you to toll-free numbers to over 300 organizations. You can access this database directly at http://www.sis.nlm.nih.gov/hotlines/. On this page, you are given the option to search by keyword or by browsing the subject list. When you have received your search results, click on the name of the organization for its description and contact information.

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The Combined Health Information Database Another comprehensive source of information on healthcare associations is the Combined Health Information Database. Using the “Detailed Search” option, you will need to limit your search to “Organizations” and “obsessive compulsive disorder”. Type the following hyperlink into your Web browser: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For publication date, select “All Years.” Then, select your preferred language and the format option “Organization Resource Sheet.” Type “obsessive compulsive disorder” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months. The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by health topic. You can access this database at the following Web site: http://www.rarediseases.org/search/orgsearch.html. Type “obsessive compulsive disorder” (or a synonym) into the search box, and click “Submit Query.”

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APPENDIX C. FINDING MEDICAL LIBRARIES Overview In this Appendix, we show you how to quickly find a medical library in your area.

Preparation Your local public library and medical libraries have interlibrary loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.26

Finding a Local Medical Library The quickest method to locate medical libraries is to use the Internet-based directory published by the National Network of Libraries of Medicine (NN/LM). This network includes 4626 members and affiliates that provide many services to librarians, health professionals, and the public. To find a library in your area, simply visit http://nnlm.gov/members/adv.html or call 1-800-338-7657.

Medical Libraries in the U.S. and Canada In addition to the NN/LM, the National Library of Medicine (NLM) lists a number of libraries with reference facilities that are open to the public. The following is the NLM’s list and includes hyperlinks to each library’s Web site. These Web pages can provide information on hours of operation and other restrictions. The list below is a small sample of

26

Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.

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libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located)27: •

Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/

•

Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)

•

Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm

•

California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html

•

California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html

•

California: Consumer Health Program and Services (CHIPS) (County of Los Angeles Public Library, Los Angeles County Harbor-UCLA Medical Center Library) - Carson, CA, http://www.colapublib.org/services/chips.html

•

California: Gateway Health Library (Sutter Gould Medical Foundation)

•

California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/

•

California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp

•

California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html

•

California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/

•

California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/

•

California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/

•

California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html

•

California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/

•

Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/

•

Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/

•

Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/

27

Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.

Finding Medical Libraries

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•

Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml

•

Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute, Wilmington), http://www.christianacare.org/health_guide/health_guide_pmri_health_info.cfm

•

Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html

•

Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm

•

Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp

•

Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/

•

Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm

•

Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html

•

Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/

•

Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm

•

Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/

•

Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/

•

Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/

•

Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm

•

Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html

•

Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm

•

Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/

•

Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/

•

Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10

•

Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/

164 Obsessive Compulsive Disorder

•

Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html

•

Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp

•

Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp

•

Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/

•

Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html

•

Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm

•

Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp

•

Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/

•

Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html

•

Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/

•

Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm

•

Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/

•

Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html

•

Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center, Ann Arbor), http://www.cancer.med.umich.edu/learn/leares.htm

•

Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330

•

Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)

•

National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html

•

National: National Network of Libraries of Medicine (National Library of Medicine) provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/

•

National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/

Finding Medical Libraries

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Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm

•

New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/

•

New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm

•

New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm

•

New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/

•

New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html

•

New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/

•

New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html

•

New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/

•

Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm

•

Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp

•

Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/

•

Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/

•

Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml

•

Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html

•

Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html

•

Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml

•

Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp

•

Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm

•

Quebec, Canada: Medical Library (Montreal General Hospital), http://www.mghlib.mcgill.ca/

166 Obsessive Compulsive Disorder

•

South Dakota: Rapid City Regional Hospital Medical Library (Rapid City Regional Hospital), http://www.rcrh.org/Services/Library/Default.asp

•

Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/

•

Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/

•

Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72

167

ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: •

ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html

•

MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp

•

Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/

•

Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html

•

On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/

•

Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp

•

Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm

Beyond these, MEDLINEplus contains a very patient-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia can be accessed at http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as drkoop.com (http://www.drkoop.com/) and Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a). The NIH suggests the following Web sites in the ADAM Medical Encyclopedia when searching for information on obsessive compulsive disorder: •

Basic Guidelines for Obsessive Compulsive Disorder Compulsive gambling Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001520.htm Ocd Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000929.htm

•

Signs & Symptoms for Obsessive Compulsive Disorder Anxiety Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003211.htm

168 Obsessive Compulsive Disorder

Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: •

Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical

•

MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html

•

Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/

•

Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine

169

OBSESSIVE COMPULSIVE DISORDER DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 3-dimensional: 3-D. A graphic display of depth, width, and height. Three-dimensional radiation therapy uses computers to create a 3-dimensional picture of the tumor. This allows doctors to give the highest possible dose of radiation to the tumor, while sparing the normal tissue as much as possible. [NIH] Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Aberrant: Wandering or deviating from the usual or normal course. [EU] Accommodation: Adjustment, especially that of the eye for various distances. [EU] Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] Activities of Daily Living: The performance of the basic activities of self care, such as dressing, ambulation, eating, etc., in rehabilitation. [NIH] Acute renal: A condition in which the kidneys suddenly stop working. In most cases, kidneys can recover from almost complete loss of function. [NIH] Acyl: Chemical signal used by bacteria to communicate. [NIH] Adaptation: 1. The adjustment of an organism to its environment, or the process by which it enhances such fitness. 2. The normal ability of the eye to adjust itself to variations in the intensity of light; the adjustment to such variations. 3. The decline in the frequency of firing of a neuron, particularly of a receptor, under conditions of constant stimulation. 4. In dentistry, (a) the proper fitting of a denture, (b) the degree of proximity and interlocking of restorative material to a tooth preparation, (c) the exact adjustment of bands to teeth. 5. In microbiology, the adjustment of bacterial physiology to a new environment. [EU] Adipose Tissue: Connective tissue composed of fat cells lodged in the meshes of areolar tissue. [NIH] Adjunctive Therapy: Another treatment used together with the primary treatment. Its purpose is to assist the primary treatment. [NIH] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH] Adolescence: The period of life beginning with the appearance of secondary sex characteristics and terminating with the cessation of somatic growth. The years usually referred to as adolescence lie between 13 and 18 years of age. [NIH] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids,

170 Obsessive Compulsive Disorder

androgens, and glucocorticoids. [NIH] Adrenal Medulla: The inner part of the adrenal gland; it synthesizes, stores and releases catecholamines. [NIH] Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Adrenergic Agonists: Drugs that bind to and activate adrenergic receptors. [NIH] Adverse Effect: An unwanted side effect of treatment. [NIH] Afferent: Concerned with the transmission of neural impulse toward the central part of the nervous system. [NIH] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Affinity Chromatography: In affinity chromatography, a ligand attached to a column binds specifically to the molecule to be purified. [NIH] Agar: A complex sulfated polymer of galactose units, extracted from Gelidium cartilagineum, Gracilaria confervoides, and related red algae. It is used as a gel in the preparation of solid culture media for microorganisms, as a bulk laxative, in making emulsions, and as a supporting medium for immunodiffusion and immunoelectrophoresis. [NIH]

Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Agoraphobia: Obsessive, persistent, intense fear of open places. [NIH] Airway: A device for securing unobstructed passage of air into and out of the lungs during general anesthesia. [NIH] Akathisia: 1. A condition of motor restlessness in which there is a feeling of muscular quivering, an urge to move about constantly, and an inability to sit still, a common extrapyramidal side effect of neuroleptic drugs. 2. An inability to sit down because of intense anxiety at the thought of doing so. [EU] Albumin: 1. Any protein that is soluble in water and moderately concentrated salt solutions and is coagulable by heat. 2. Serum albumin; the major plasma protein (approximately 60 per cent of the total), which is responsible for much of the plasma colloidal osmotic pressure and serves as a transport protein carrying large organic anions, such as fatty acids, bilirubin, and many drugs, and also carrying certain hormones, such as cortisol and thyroxine, when their specific binding globulins are saturated. Albumin is synthesized in the liver. Low serum levels occur in protein malnutrition, active inflammation and serious hepatic and renal disease. [EU] Albuterol: A racemic mixture with a 1:1 ratio of the r-isomer, levalbuterol, and s-albuterol. It

Dictionary 171

is a short-acting beta 2-adrenergic agonist with its main clinical use in asthma. [NIH] Alexia: The inability to recognize or comprehend written or printed words. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alkaline: Having the reactions of an alkali. [EU] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] Allergen: An antigenic substance capable of producing immediate-type hypersensitivity (allergy). [EU] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Amenorrhea: Absence of menstruation. [NIH] Amine: An organic compound containing nitrogen; any member of a group of chemical compounds formed from ammonia by replacement of one or more of the hydrogen atoms by organic (hydrocarbon) radicals. The amines are distinguished as primary, secondary, and tertiary, according to whether one, two, or three hydrogen atoms are replaced. The amines include allylamine, amylamine, ethylamine, methylamine, phenylamine, propylamine, and many other compounds. [EU] Amino Acid Neurotransmitters: Amino acids released by neurons as intercellular messengers. Among the amino acid neurotransmitters are glutamate (glutamic acid) and GABA which are, respectively, the most common excitatory and inhibitory neurotransmitters in the central nervous system. [NIH] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amnesia: Lack or loss of memory; inability to remember past experiences. [EU] Amnestic: Nominal aphasia; a difficulty in finding the right name for an object. [NIH] Amniotic Fluid: Amniotic cavity fluid which is produced by the amnion and fetal lungs and kidneys. [NIH] Amphetamine: A powerful central nervous system stimulant and sympathomimetic. Amphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulation of release of monamines, and inhibiting monoamine oxidase. Amphetamine is also a drug of abuse and a psychotomimetic. The l- and the d,l-forms are included here. The l-form has less central nervous system activity but stronger

172 Obsessive Compulsive Disorder

cardiovascular effects. The d-form is dextroamphetamine. [NIH] Amygdala: Almond-shaped group of basal nuclei anterior to the inferior horn of the lateral ventricle of the brain, within the temporal lobe. The amygdala is part of the limbic system. [NIH]

Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] Analgesic: An agent that alleviates pain without causing loss of consciousness. [EU] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Anomalies: Birth defects; abnormalities. [NIH] Anorexia: Lack or loss of appetite for food. Appetite is psychologic, dependent on memory and associations. Anorexia can be brought about by unattractive food, surroundings, or company. [NIH] Anorexia Nervosa: The chief symptoms are inability to eat, weight loss, and amenorrhea. [NIH]

Antecedent: Existing or occurring before in time or order often with consequential effects. [EU]

Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]

Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Anticonvulsant: An agent that prevents or relieves convulsions. [EU] Antidepressant: A drug used to treat depression. [NIH] Antidiuretic: Suppressing the rate of urine formation. [EU] Antiemetic: An agent that prevents or alleviates nausea and vomiting. Also antinauseant. [EU]

Dictionary 173

Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antihypertensive: An agent that reduces high blood pressure. [EU] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Antimetabolite: A chemical that is very similar to one required in a normal biochemical reaction in cells. Antimetabolites can stop or slow down the reaction. [NIH] Antimicrobial: Killing microorganisms, or suppressing their multiplication or growth. [EU] Antipsychotic: Effective in the treatment of psychosis. Antipsychotic drugs (called also neuroleptic drugs and major tranquilizers) are a chemically diverse (including phenothiazines, thioxanthenes, butyrophenones, dibenzoxazepines, dibenzodiazepines, and diphenylbutylpiperidines) but pharmacologically similar class of drugs used to treat schizophrenic, paranoid, schizoaffective, and other psychotic disorders; acute delirium and dementia, and manic episodes (during induction of lithium therapy); to control the movement disorders associated with Huntington's chorea, Gilles de la Tourette's syndrome, and ballismus; and to treat intractable hiccups and severe nausea and vomiting. Antipsychotic agents bind to dopamine, histamine, muscarinic cholinergic, a-adrenergic, and serotonin receptors. Blockade of dopaminergic transmission in various areas is thought to be responsible for their major effects : antipsychotic action by blockade in the mesolimbic and mesocortical areas; extrapyramidal side effects (dystonia, akathisia, parkinsonism, and tardive dyskinesia) by blockade in the basal ganglia; and antiemetic effects by blockade in the chemoreceptor trigger zone of the medulla. Sedation and autonomic side effects (orthostatic hypotension, blurred vision, dry mouth, nasal congestion and constipation) are caused by blockade of histamine, cholinergic, and adrenergic receptors. [EU] Antipsychotic Agents: Agents that control agitated psychotic behavior, alleviate acute psychotic states, reduce psychotic symptoms, and exert a quieting effect. They are used in schizophrenia, senile dementia, transient psychosis following surgery or myocardial infarction, etc. These drugs are often referred to as neuroleptics alluding to the tendency to produce neurological side effects, but not all antipsychotics are likely to produce such effects. Many of these drugs may also be effective against nausea, emesis, and pruritus. [NIH] Antiviral: Destroying viruses or suppressing their replication. [EU] Anus: The opening of the rectum to the outside of the body. [NIH] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Anxiety Disorders: Disorders in which anxiety (persistent feelings of apprehension, tension, or uneasiness) is the predominant disturbance. [NIH] Anxiolytic: An anxiolytic or antianxiety agent. [EU] Aorta: The main trunk of the systemic arteries. [NIH] Apathy: Lack of feeling or emotion; indifference. [EU] Aphasia: A cognitive disorder marked by an impaired ability to comprehend or express language in its written or spoken form. This condition is caused by diseases which affect the language areas of the dominant hemisphere. Clinical features are used to classify the various subtypes of this condition. General categories include receptive, expressive, and mixed forms of aphasia. [NIH]

174 Obsessive Compulsive Disorder

Apnea: A transient absence of spontaneous respiration. [NIH] Apomorphine: A derivative of morphine that is a dopamine D2 agonist. It is a powerful emetic and has been used for that effect in acute poisoning. It has also been used in the diagnosis and treatment of parkinsonism, but its adverse effects limit its use. [NIH] Aqueous: Having to do with water. [NIH] Arachidonic Acid: An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Aromatic: Having a spicy odour. [EU] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Arteriolosclerosis: Sclerosis and thickening of the walls of the smaller arteries (arterioles). Hyaline arteriolosclerosis, in which there is homogeneous pink hyaline thickening of the arteriolar walls, is associated with benign nephrosclerosis. Hyperplastic arteriolosclerosis, in which there is a concentric thickening with progressive narrowing of the lumina may be associated with malignant hypertension, nephrosclerosis, and scleroderma. [EU] Arteriosclerosis: Thickening and loss of elasticity of arterial walls. Atherosclerosis is the most common form of arteriosclerosis and involves lipid deposition and thickening of the intimal cell layers within arteries. Additional forms of arteriosclerosis involve calcification of the media of muscular arteries (Monkeberg medial calcific sclerosis) and thickening of the walls of small arteries or arterioles due to cell proliferation or hyaline deposition (arteriolosclerosis). [NIH] Articular: Of or pertaining to a joint. [EU] Articulation: The relationship of two bodies by means of a moveable joint. [NIH] Artifacts: Any visible result of a procedure which is caused by the procedure itself and not by the entity being analyzed. Common examples include histological structures introduced by tissue processing, radiographic images of structures that are not naturally present in living tissue, and products of chemical reactions that occur during analysis. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Astrocytes: The largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from "star" cells) are irregularly shaped with many long processes, including those with "end feet" which form the glial (limiting) membrane and directly and indirectly contribute to the blood brain barrier. They regulate the extracellular ionic and chemical environment, and "reactive astrocytes" (along with microglia) respond to injury. Astrocytes have high- affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitter, but their role in signaling (as in many other functions) is not well understood. [NIH] Atrial: Pertaining to an atrium. [EU] Atrioventricular: Pertaining to an atrium of the heart and to a ventricle. [EU] Atrium: A chamber; used in anatomical nomenclature to designate a chamber affording entrance to another structure or organ. Usually used alone to designate an atrium of the

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heart. [EU] Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to strains of unusual type. [EU] Auditory: Pertaining to the sense of hearing. [EU] Autacoids: A chemically diverse group of substances produced by various tissues in the body that cause slow contraction of smooth muscle; they have other intense but varied pharmacologic activities. [NIH] Autoantibodies: Antibodies that react with self-antigens (autoantigens) of the organism that produced them. [NIH] Autoantigens: Endogenous tissue constituents that have the ability to interact with autoantibodies and cause an immune response. [NIH] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH] Autonomic: Self-controlling; functionally independent. [EU] Autoradiography: A process in which radioactive material within an object produces an image when it is in close proximity to a radiation sensitive emulsion. [NIH] Autoreceptors: Transmitter receptors on or near presynaptic terminals (or varicosities) which are sensitive to the transmitter(s) released by the terminal itself. Receptors for the hormones released by hormone-releasing cells are also included. [NIH] Baclofen: A GABA derivative that is a specific agonist at GABA-B receptors. It is used in the treatment of spasticity, especially that due to spinal cord damage. Its therapeutic effects result from actions at spinal and supraspinal sites, generally the reduction of excitatory transmission. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bacterial Physiology: Physiological processes and activities of bacteria. [NIH] Bactericidal: Substance lethal to bacteria; substance capable of killing bacteria. [NIH] Bacteriophage: A virus whose host is a bacterial cell; A virus that exclusively infects bacteria. It generally has a protein coat surrounding the genome (DNA or RNA). One of the coliphages most extensively studied is the lambda phage, which is also one of the most important. [NIH] Bacterium: Microscopic organism which may have a spherical, rod-like, or spiral unicellular or non-cellular body. Bacteria usually reproduce through asexual processes. [NIH] Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [NIH] Basal Ganglia Diseases: Diseases of the basal ganglia including the putamen; globus pallidus; claustrum; amygdala; and caudate nucleus. Dyskinesias (most notably involuntary movements and alterations of the rate of movement) represent the primary clinical manifestations of these disorders. Common etiologies include cerebrovascular disease; neurodegenerative diseases; and craniocerebral trauma. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Behavior Therapy: The application of modern theories of learning and conditioning in the

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treatment of behavior disorders. [NIH] Behavioral Symptoms: Observable manifestions of impaired psychological functioning. [NIH]

Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]

Bewilderment: Impairment or loss of will power. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Bioavailability: The degree to which a drug or other substance becomes available to the target tissue after administration. [EU] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biogenic Amines: A group of naturally occurring amines derived by enzymatic decarboxylation of the natural amino acids. Many have powerful physiological effects (e.g., histamine, serotonin, epinephrine, tyramine). Those derived from aromatic amino acids, and also their synthetic analogs (e.g., amphetamine), are of use in pharmacology. [NIH] Biological Markers: Measurable and quantifiable biological parameters (e.g., specific enzyme concentration, specific hormone concentration, specific gene phenotype distribution in a population, presence of biological substances) which serve as indices for health- and physiology-related assessments, such as disease risk, psychiatric disorders, environmental exposure and its effects, disease diagnosis, metabolic processes, substance abuse, pregnancy, cell line development, epidemiologic studies, etc. [NIH] Biological Psychiatry: An interdisciplinary science concerned with studies of the biological bases of behavior - biochemical, genetic, physiological, and neurological - and applying these to the understanding and treatment of mental illness. [NIH] Biological Sciences: All of the divisions of the natural sciences dealing with the various aspects of the phenomena of life and vital processes. The concept includes anatomy and physiology, biochemistry and biophysics, and the biology of animals, plants, and microorganisms. It should be differentiated from biology, one of its subdivisions, concerned specifically with the origin and life processes of living organisms. [NIH] Biological Transport: The movement of materials (including biochemical substances and drugs) across cell membranes and epithelial layers, usually by passive diffusion. [NIH] Biophysics: The science of physical phenomena and processes in living organisms. [NIH] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] Biosynthesis: The building up of a chemical compound in the physiologic processes of a living organism. [EU] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Bipolar Disorder: A major affective disorder marked by severe mood swings (manic or major depressive episodes) and a tendency to remission and recurrence. [NIH] Bladder: The organ that stores urine. [NIH]

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Blastocyst: The mammalian embryo in the post-morula stage in which a fluid-filled cavity, enclosed primarily by trophoblast, contains an inner cell mass which becomes the embryonic disc. [NIH] Blinking: Brief closing of the eyelids by involuntary normal periodic closing, as a protective measure, or by voluntary action. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Platelets: Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Blood-Brain Barrier: Specialized non-fenestrated tightly-joined endothelial cells (tight junctions) that form a transport barrier for certain substances between the cerebral capillaries and the brain tissue. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Bowel Movement: Body wastes passed through the rectum and anus. [NIH] Bradykinin: A nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [NIH] Brain Diseases: Pathologic conditions affecting the brain, which is composed of the intracranial components of the central nervous system. This includes (but is not limited to) the cerebral cortex; intracranial white matter; basal ganglia; thalamus; hypothalamus; brain stem; and cerebellum. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]

Bronchial: Pertaining to one or more bronchi. [EU] Bronchodilator: A drug that relaxes the smooth muscles in the constricted airway. [NIH] Bulimia: Episodic binge eating. The episodes may be associated with the fear of not being able to stop eating, depressed mood, or self-deprecating thoughts (binge-eating disorder) and may frequently be terminated by self-induced vomiting (bulimia nervosa). [NIH] Bupropion: A unicyclic, aminoketone antidepressant. The mechanism of its therapeutic actions is not well understood, but it does appear to block dopamine uptake. The hydrochloride is available as an aid to smoking cessation treatment. [NIH] Calcification: Deposits of calcium in the tissues of the breast. Calcification in the breast can be seen on a mammogram, but cannot be detected by touch. There are two types of breast calcification, macrocalcification and microcalcification. Macrocalcifications are large deposits and are usually not related to cancer. Microcalcifications are specks of calcium that may be found in an area of rapidly dividing cells. Many microcalcifications clustered together may be a sign of cancer. [NIH]

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Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Calcium channel blocker: A drug used to relax the blood vessel and heart muscle, causing pressure inside blood vessels to drop. It also can regulate heart rhythm. [NIH] Calcium Channel Blockers: A class of drugs that act by selective inhibition of calcium influx through cell membranes or on the release and binding of calcium in intracellular pools. Since they are inducers of vascular and other smooth muscle relaxation, they are used in the drug therapy of hypertension and cerebrovascular spasms, as myocardial protective agents, and in the relaxation of uterine spasms. [NIH] Calculi: An abnormal concretion occurring mostly in the urinary and biliary tracts, usually composed of mineral salts. Also called stones. [NIH] Carbamazepine: An anticonvulsant used to control grand mal and psychomotor or focal seizures. Its mode of action is not fully understood, but some of its actions resemble those of phenytoin; although there is little chemical resemblance between the two compounds, their three-dimensional structure is similar. [NIH] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU] Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. [NIH] Carcinogenic: Producing carcinoma. [EU] Cardiac: Having to do with the heart. [NIH] Cardiac arrest: A sudden stop of heart function. [NIH] Cardiac Output: The volume of blood passing through the heart per unit of time. It is usually expressed as liters (volume) per minute so as not to be confused with stroke volume (volume per beat). [NIH] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular disease: Any abnormal condition characterized by dysfunction of the heart and blood vessels. CVD includes atherosclerosis (especially coronary heart disease, which can lead to heart attacks), cerebrovascular disease (e.g., stroke), and hypertension (high blood pressure). [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Case series: A group or series of case reports involving patients who were given similar treatment. Reports of case series usually contain detailed information about the individual patients. This includes demographic information (for example, age, gender, ethnic origin) and information on diagnosis, treatment, response to treatment, and follow-up after treatment. [NIH] Catalogs: Ordered compilations of item descriptions and sufficient information to afford access to them. [NIH]

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Catecholamine: A group of chemical substances manufactured by the adrenal medulla and secreted during physiological stress. [NIH] Caudal: Denoting a position more toward the cauda, or tail, than some specified point of reference; same as inferior, in human anatomy. [EU] Caudate Nucleus: Elongated gray mass of the neostriatum located adjacent to the lateral ventricle of the brain. [NIH] Causal: Pertaining to a cause; directed against a cause. [EU] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function which takes place during the development of the embryo and leads to the formation of specialized cells, tissues, and organs. [NIH] Cell Division: The fission of a cell. [NIH] Cell membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Central Nervous System Infections: Pathogenic infections of the brain, spinal cord, and meninges. DNA virus infections; RNA virus infections; bacterial infections; mycoplasma infections; Spirochaetales infections; fungal infections; protozoan infections; helminthiasis; and prion diseases may involve the central nervous system as a primary or secondary process. [NIH] Cerebellum: Part of the metencephalon that lies in the posterior cranial fossa behind the brain stem. It is concerned with the coordination of movement. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral Arteries: The arteries supplying the cerebral cortex. [NIH] Cerebrospinal: Pertaining to the brain and spinal cord. [EU] Cerebrospinal fluid: CSF. The fluid flowing around the brain and spinal cord. Cerebrospinal fluid is produced in the ventricles in the brain. [NIH] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Chemoreceptor: A receptor adapted for excitation by chemical substances, e.g., olfactory and gustatory receptors, or a sense organ, as the carotid body or the aortic (supracardial) bodies, which is sensitive to chemical changes in the blood stream, especially reduced oxygen content, and reflexly increases both respiration and blood pressure. [EU] Child Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders in children. [NIH] Child Psychology: The study of normal and abnormal behavior of children. [NIH] Chlorpromazine: The prototypical phenothiazine antipsychotic drug. Like the other drugs

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in this class chlorpromazine's antipsychotic actions are thought to be due to long-term adaptation by the brain to blocking dopamine receptors. Chlorpromazine has several other actions and therapeutic uses, including as an antiemetic and in the treatment of intractable hiccup. [NIH] Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] Cholinergic: Resembling acetylcholine in pharmacological action; stimulated by or releasing acetylcholine or a related compound. [EU] Chorea: Involuntary, forcible, rapid, jerky movements that may be subtle or become confluent, markedly altering normal patterns of movement. Hypotonia and pendular reflexes are often associated. Conditions which feature recurrent or persistent episodes of chorea as a primary manifestation of disease are referred to as choreatic disorders. Chorea is also a frequent manifestation of basal ganglia diseases. [NIH] Choreatic Disorders: Acquired and hereditary conditions which feature chorea as a primary manifestation of the disease process. [NIH] Chromosomal: Pertaining to chromosomes. [EU] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Circadian: Repeated more or less daily, i. e. on a 23- to 25-hour cycle. [NIH] Circadian Rhythm: The regular recurrence, in cycles of about 24 hours, of biological processes or activities, such as sensitivity to drugs and stimuli, hormone secretion, sleeping, feeding, etc. This rhythm seems to be set by a 'biological clock' which seems to be set by recurring daylight and darkness. [NIH] CIS: Cancer Information Service. The CIS is the National Cancer Institute's link to the public, interpreting and explaining research findings in a clear and understandable manner, and providing personalized responses to specific questions about cancer. Access the CIS by calling 1-800-4-CANCER, or by using the Web site at http://cis.nci.nih.gov. [NIH] Cisplatin: An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle. [NIH] Citalopram: A selective neuronal serotonin reuptake inhibitor and a clinically effective antidepressant with tolerable side effects. The drug is also effective in reducing ethanol uptake in alcoholics and is used in depressed patients who also suffer from tardive dyskinesia (TD) in preference to tricyclic antidepressants, which aggravate this condition. [NIH]

Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Clomipramine: A tricyclic antidepressant similar to imipramine that selectively inhibits the uptake of serotonin in the brain. It is readily absorbed from the gastrointestinal tract and demethylated in the liver to form its primary active metabolite, desmethylclomipramine. [NIH]

Clonazepam: An anticonvulsant used for several types of seizures, including myotonic or atonic seizures, photosensitive epilepsy, and absence seizures, although tolerance may develop. It is seldom effective in generalized tonic-clonic or partial seizures. The mechanism

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of action appears to involve the enhancement of gaba receptor responses. [NIH] Clone: The term "clone" has acquired a new meaning. It is applied specifically to the bits of inserted foreign DNA in the hybrid molecules of the population. Each inserted segment originally resided in the DNA of a complex genome amid millions of other DNA segment. [NIH]

Clonic: Pertaining to or of the nature of clonus. [EU] Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Clot Retraction: Retraction of a clot resulting from contraction of platelet pseudopods attached to fibrin strands that is dependent on the contractile protein thrombosthenin. Used as a measure of platelet function. [NIH] Coagulation: 1. The process of clot formation. 2. In colloid chemistry, the solidification of a sol into a gelatinous mass; an alteration of a disperse phase or of a dissolved solid which causes the separation of the system into a liquid phase and an insoluble mass called the clot or curd. Coagulation is usually irreversible. 3. In surgery, the disruption of tissue by physical means to form an amorphous residuum, as in electrocoagulation and photocoagulation. [EU] Coca: Any of several South American shrubs of the Erythroxylon genus (and family) that yield cocaine; the leaves are chewed with alum for CNS stimulation. [NIH] Cocaine: An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake. [NIH] Cochlear: Of or pertaining to the cochlea. [EU] Cochlear Diseases: Diseases of the cochlea, the part of the inner ear that is concerned with hearing. [NIH] Coenzymes: Substances that are necessary for the action or enhancement of action of an enzyme. Many vitamins are coenzymes. [NIH] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Cognition: Intellectual or mental process whereby an organism becomes aware of or obtains knowledge. [NIH] Cognitive behavior therapy: A system of psychotherapy based on the premise that distorted or dysfunctional thinking, which influences a person's mood or behavior, is common to all psychosocial problems. The focus of therapy is to identify the distorted thinking and to replace it with more rational, adaptive thoughts and beliefs. [NIH] Cognitive Therapy: A direct form of psychotherapy based on the interpretation of situations (cognitive structure of experiences) that determine how an individual feels and behaves. It is based on the premise that cognition, the process of acquiring knowledge and forming beliefs, is a primary determinant of mood and behavior. The therapy uses behavioral and verbal techniques to identify and correct negative thinking that is at the root of the aberrant behavior. [NIH] Cohort Studies: Studies in which subsets of a defined population are identified. These groups may or may not be exposed to factors hypothesized to influence the probability of

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the occurrence of a particular disease or other outcome. Cohorts are defined populations which, as a whole, are followed in an attempt to determine distinguishing subgroup characteristics. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Collapse: 1. A state of extreme prostration and depression, with failure of circulation. 2. Abnormal falling in of the walls of any part of organ. [EU] Comorbidity: The presence of co-existing or additional diseases with reference to an initial diagnosis or with reference to the index condition that is the subject of study. Comorbidity may affect the ability of affected individuals to function and also their survival; it may be used as a prognostic indicator for length of hospital stay, cost factors, and outcome or survival. [NIH] Competency: The capacity of the bacterium to take up DNA from its surroundings. [NIH] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such

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as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complete remission: The disappearance of all signs of cancer. Also called a complete response. [NIH] Compulsion: In psychology, an irresistible urge, sometimes amounting to obsession to perform a particular act which usually is carried out against the performer's will or better judgment. [NIH] Compulsive Behavior: The behavior of performing an act persistently and repetitively without it leading to reward or pleasure. The act is usually a small, circumscribed behavior, almost ritualistic, yet not pathologically disturbing. Examples of compulsive behavior include twirling of hair, checking something constantly, not wanting pennies in change, straightening tilted pictures, etc. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Computed tomography: CT scan. A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized tomography and computerized axial tomography (CAT) scan. [NIH] Computer Simulation: Computer-based representation of physical systems and phenomena such as chemical processes. [NIH] Computerized axial tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called CAT scan, computed tomography (CT scan), or computerized tomography. [NIH] Computerized tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized axial tomography (CAT) scan and computed tomography (CT scan). [NIH] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [EU] Concomitant: Accompanying; accessory; joined with another. [EU] Confusion: A mental state characterized by bewilderment, emotional disturbance, lack of clear thinking, and perceptual disorientation. [NIH] Congestion: Excessive or abnormal accumulation of blood in a part. [EU] Congestive heart failure: Weakness of the heart muscle that leads to a buildup of fluid in body tissues. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Consciousness: Sense of awareness of self and of the environment. [NIH] Constipation: Infrequent or difficult evacuation of feces. [NIH] Constriction: The act of constricting. [NIH] Constriction, Pathologic: The condition of an anatomical structure's being constricted

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beyond normal dimensions. [NIH] Contamination: The soiling or pollution by inferior material, as by the introduction of organisms into a wound, or sewage into a stream. [EU] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Control group: In a clinical trial, the group that does not receive the new treatment being studied. This group is compared to the group that receives the new treatment, to see if the new treatment works. [NIH] Controlled study: An experiment or clinical trial that includes a comparison (control) group. [NIH]

Convulsions: A general term referring to sudden and often violent motor activity of cerebral or brainstem origin. Convulsions may also occur in the absence of an electrical cerebral discharge (e.g., in response to hypotension). [NIH] Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH] Cor: The muscular organ that maintains the circulation of the blood. c. adiposum a heart that has undergone fatty degeneration or that has an accumulation of fat around it; called also fat or fatty, heart. c. arteriosum the left side of the heart, so called because it contains oxygenated (arterial) blood. c. biloculare a congenital anomaly characterized by failure of formation of the atrial and ventricular septums, the heart having only two chambers, a single atrium and a single ventricle, and a common atrioventricular valve. c. bovinum (L. 'ox heart') a greatly enlarged heart due to a hypertrophied left ventricle; called also c. taurinum and bucardia. c. dextrum (L. 'right heart') the right atrium and ventricle. c. hirsutum, c. villosum. c. mobile (obs.) an abnormally movable heart. c. pendulum a heart so movable that it seems to be hanging by the great blood vessels. c. pseudotriloculare biatriatum a congenital cardiac anomaly in which the heart functions as a three-chambered heart because of tricuspid atresia, the right ventricle being extremely small or rudimentary and the right atrium greatly dilated. Blood passes from the right to the left atrium and thence disease due to pulmonary hypertension secondary to disease of the lung, or its blood vessels, with hypertrophy of the right ventricle. [EU] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary heart disease: A type of heart disease caused by narrowing of the coronary arteries that feed the heart, which needs a constant supply of oxygen and nutrients carried by the blood in the coronary arteries. When the coronary arteries become narrowed or clogged by fat and cholesterol deposits and cannot supply enough blood to the heart, CHD results. [NIH] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Corpus: The body of the uterus. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Cortical: Pertaining to or of the nature of a cortex or bark. [EU] Cortisol: A steroid hormone secreted by the adrenal cortex as part of the body's response to stress. [NIH] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans)

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end of the body. [EU] Craniocerebral Trauma: Traumatic injuries involving the cranium and intracranial structures (i.e., brain; cranial nerves; meninges; and other structures). Injuries may be classified by whether or not the skull is penetrated (i.e., penetrating vs. nonpenetrating) or whether there is an associated hemorrhage. [NIH] Cross-Sectional Studies: Studies in which the presence or absence of disease or other health-related variables are determined in each member of the study population or in a representative sample at one particular time. This contrasts with longitudinal studies which are followed over a period of time. [NIH] Cues: Signals for an action; that specific portion of a perceptual field or pattern of stimuli to which a subject has learned to respond. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cutaneous: Having to do with the skin. [NIH] Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU] Cytogenetics: A branch of genetics which deals with the cytological and molecular behavior of genes and chromosomes during cell division. [NIH] Cytotoxic: Cell-killing. [NIH] Cytotoxic chemotherapy: Anticancer drugs that kill cells, especially cancer cells. [NIH] Databases, Bibliographic: Extensive collections, reputedly complete, of references and citations to books, articles, publications, etc., generally on a single subject or specialized subject area. Databases can operate through automated files, libraries, or computer disks. The concept should be differentiated from factual databases which is used for collections of data and facts apart from bibliographic references to them. [NIH] Deamination: The removal of an amino group (NH2) from a chemical compound. [NIH] Decarboxylation: The removal of a carboxyl group, usually in the form of carbon dioxide, from a chemical compound. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Delirium: (DSM III-R) an acute, reversible organic mental disorder characterized by reduced ability to maintain attention to external stimuli and disorganized thinking as manifested by rambling, irrelevant, or incoherent speech; there are also a reduced level of consciousness, sensory misperceptions, disturbance of the sleep-wakefulness cycle and level of psychomotor activity, disorientation to time, place, or person, and memory impairment. Delirium may be caused by a large number of conditions resulting in derangement of cerebral metabolism, including systemic infection, poisoning, drug intoxication or withdrawal, seizures or head trauma, and metabolic disturbances such as hypoxia, hypoglycaemia, fluid, electrolyte, or acid-base imbalances, or hepatic or renal failure. Called also acute confusional state and acute brain syndrome. [EU] Delusions: A false belief regarding the self or persons or objects outside the self that persists despite the facts, and is not considered tenable by one's associates. [NIH] Dementia: An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness. [NIH]

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Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Dendritic: 1. Branched like a tree. 2. Pertaining to or possessing dendrites. [EU] Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Deoxyglucose: 2-Deoxy-D-arabino-hexose. An antimetabolite of glucose with antiviral activity. [NIH] Depersonalization: Alteration in the perception of the self so that the usual sense of one's own reality is lost, manifested in a sense of unreality or self-estrangement, in changes of body image, or in a feeling that one does not control his own actions and speech; seen in depersonalization disorder, schizophrenic disorders, and schizotypal personality disorder. Some do not draw a distinction between depersonalization and derealization, using depersonalization to include both. [EU] Depolarization: The process or act of neutralizing polarity. In neurophysiology, the reversal of the resting potential in excitable cell membranes when stimulated, i.e., the tendency of the cell membrane potential to become positive with respect to the potential outside the cell. [EU] Depressive Disorder: An affective disorder manifested by either a dysphoric mood or loss of interest or pleasure in usual activities. The mood disturbance is prominent and relatively persistent. [NIH] Derealization: Is characterized by the loss of the sense of reality concerning one's surroundings. [NIH] Dermatitis: Any inflammation of the skin. [NIH] Desensitization: The prevention or reduction of immediate hypersensitivity reactions by administration of graded doses of allergen; called also hyposensitization and immunotherapy. [EU] Detoxification: Treatment designed to free an addict from his drug habit. [EU] Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [NIH] Dextroamphetamine: The d-form of amphetamine. It is a central nervous system stimulant and a sympathomimetic. It has also been used in the treatment of narcolepsy and of attention deficit disorders and hyperactivity in children. Dextroamphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulating release of monamines, and inhibiting monoamine oxidase. It is also a drug of abuse and a psychotomimetic. [NIH] Diabetes Insipidus: A metabolic disorder due to disorders in the production or release of vasopressin. It is characterized by the chronic excretion of large amounts of low specific gravity urine and great thirst. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diastolic: Of or pertaining to the diastole. [EU] Diencephalon: The paired caudal parts of the prosencephalon from which the thalamus, hypothalamus, epithalamus, and subthalamus are derived. [NIH] Diffusion: The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space; a major mechanism of biological transport. [NIH] Digestive system: The organs that take in food and turn it into products that the body can use to stay healthy. Waste products the body cannot use leave the body through bowel movements. The digestive system includes the salivary glands, mouth, esophagus, stomach,

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liver, pancreas, gallbladder, small and large intestines, and rectum. [NIH] Dilatation: The act of dilating. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Disabled Children: Children with mental or physical disabilities that interfere with usual activities of daily living and that may require accommodation or intervention. [NIH] Discrimination: The act of qualitative and/or quantitative differentiation between two or more stimuli. [NIH] Disease Susceptibility: A constitution or condition of the body which makes the tissues react in special ways to certain extrinsic stimuli and thus tends to make the individual more than usually susceptible to certain diseases. [NIH] Disinfectant: An agent that disinfects; applied particularly to agents used on inanimate objects. [EU] Disorientation: The loss of proper bearings, or a state of mental confusion as to time, place, or identity. [EU] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] Dissociative Disorders: Sudden temporary alterations in the normally integrative functions of consciousness. [NIH] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Dizziness: An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. [NIH] Dominance: In genetics, the full phenotypic expression of a gene in both heterozygotes and homozygotes. [EU] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic effects including its actions as an inotropic agent and as a renal vasodilator. [NIH] Dopamine Antagonists: Drugs that bind to but do not activate dopamine receptors, thereby blocking the actions of dopamine or exogenous agonists. Many drugs used in the treatment of psychotic disorders (antipsychotic agents) are dopamine antagonists, although their therapeutic effects may be due to long-term adjustments of the brain rather than to the acute effects of blocking dopamine receptors. Dopamine antagonists have been used for several other clinical purposes including as antiemetics, in the treatment of Tourette syndrome, and for hiccup. [NIH] Dorsal: 1. Pertaining to the back or to any dorsum. 2. Denoting a position more toward the

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back surface than some other object of reference; same as posterior in human anatomy; superior in the anatomy of quadrupeds. [EU] Dorsum: A plate of bone which forms the posterior boundary of the sella turcica. [NIH] Drive: A state of internal activity of an organism that is a necessary condition before a given stimulus will elicit a class of responses; e.g., a certain level of hunger (drive) must be present before food will elicit an eating response. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Drug Monitoring: The process of observing, recording, or detecting the effects of a chemical substance administered to an individual therapeutically or diagnostically. [NIH] Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [NIH] Ductus Arteriosus: A fetal blood vessel connecting the pulmonary artery with the descending aorta. [NIH] Dyskinesia: Impairment of the power of voluntary movement, resulting in fragmentary or incomplete movements. [EU] Dyslexia: Partial alexia in which letters but not words may be read, or in which words may be read but not understood. [NIH] Dysmenorrhea: Painful menstruation. [NIH] Dysphoria: Disquiet; restlessness; malaise. [EU] Dysphoric: A feeling of unpleasantness and discomfort. [NIH] Dyspnea: Difficult or labored breathing. [NIH] Dystonia: Disordered tonicity of muscle. [EU] Eating Disorders: A group of disorders characterized by physiological and psychological disturbances in appetite or food intake. [NIH] Eczema: A pruritic papulovesicular dermatitis occurring as a reaction to many endogenous and exogenous agents (Dorland, 27th ed). [NIH] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Effector cell: A cell that performs a specific function in response to a stimulus; usually used to describe cells in the immune system. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Ego: The conscious portion of the personality structure which serves to mediate between the demands of the primitive instinctual drives, (the id), of internalized parental and social prohibitions or the conscience, (the superego), and of reality. [NIH] Ejaculation: The release of semen through the penis during orgasm. [NIH] Elasticity: Resistance and recovery from distortion of shape. [NIH] Elective: Subject to the choice or decision of the patient or physician; applied to procedures that are advantageous to the patient but not urgent. [EU]

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Electrocoagulation: Electrosurgical procedures used to treat hemorrhage (e.g., bleeding ulcers) and to ablate tumors, mucosal lesions, and refractory arrhythmias. [NIH] Electroconvulsive Therapy: Electrically induced convulsions primarily used in the treatment of severe affective disorders and schizophrenia. [NIH] Electrode: Component of the pacing system which is at the distal end of the lead. It is the interface with living cardiac tissue across which the stimulus is transmitted. [NIH] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] Electrophysiological: Pertaining to electrophysiology, that is a branch of physiology that is concerned with the electric phenomena associated with living bodies and involved in their functional activity. [EU] Elementary Particles: Individual components of atoms, usually subatomic; subnuclear particles are usually detected only when the atomic nucleus decays and then only transiently, as most of them are unstable, often yielding pure energy without substance, i.e., radiation. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Emetic: An agent that causes vomiting. [EU] Empiric: Empirical; depending upon experience or observation alone, without using scientific method or theory. [EU] Empirical: A treatment based on an assumed diagnosis, prior to receiving confirmatory laboratory test results. [NIH] Emulsion: A preparation of one liquid distributed in small globules throughout the body of a second liquid. The dispersed liquid is the discontinuous phase, and the dispersion medium is the continuous phase. When oil is the dispersed liquid and an aqueous solution is the continuous phase, it is known as an oil-in-water emulsion, whereas when water or aqueous solution is the dispersed phase and oil or oleaginous substance is the continuous phase, it is known as a water-in-oil emulsion. Pharmaceutical emulsions for which official standards have been promulgated include cod liver oil emulsion, cod liver oil emulsion with malt, liquid petrolatum emulsion, and phenolphthalein in liquid petrolatum emulsion. [EU] Encapsulated: Confined to a specific, localized area and surrounded by a thin layer of tissue. [NIH]

Encephalitis: Inflammation of the brain due to infection, autoimmune processes, toxins, and other conditions. Viral infections (see encephalitis, viral) are a relatively frequent cause of this condition. [NIH] Endocrine System: The system of glands that release their secretions (hormones) directly into the circulatory system. In addition to the endocrine glands, included are the chromaffin system and the neurosecretory systems. [NIH] Endocrinology: A subspecialty of internal medicine concerned with the metabolism, physiology, and disorders of the endocrine system. [NIH] Endometrium: The layer of tissue that lines the uterus. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH]

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Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium, vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH] Enuresis: Involuntary discharge of urine after the age at which urinary control should have been achieved; often used alone with specific reference to involuntary discharge of urine occurring during sleep at night (bed-wetting, nocturnal enuresis). [EU] Environmental Exposure: The exposure to potentially harmful chemical, physical, or biological agents in the environment or to environmental factors that may include ionizing radiation, pathogenic organisms, or toxic chemicals. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]

Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Epidemiologic Studies: Studies designed to examine associations, commonly, hypothesized causal relations. They are usually concerned with identifying or measuring the effects of risk factors or exposures. The common types of analytic study are case-control studies, cohort studies, and cross-sectional studies. [NIH] Epidemiological: Relating to, or involving epidemiology. [EU] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Erectile: The inability to get or maintain an erection for satisfactory sexual intercourse. Also called impotence. [NIH] Erection: The condition of being made rigid and elevated; as erectile tissue when filled with blood. [EU] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]

Essential Tremor: A rhythmic, involuntary, purposeless, oscillating movement resulting from the alternate contraction and relaxation of opposing groups of muscles. [NIH] Estrogen: One of the two female sex hormones. [NIH] Ethanol: A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in alcoholic beverages. [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Evoke: The electric response recorded from the cerebral cortex after stimulation of a peripheral sense organ. [NIH] Excitatory: When cortical neurons are excited, their output increases and each new input they receive while they are still excited raises their output markedly. [NIH] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU]

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Exotoxin: Toxic substance excreted by living bacterial cells. [NIH] Extensor: A muscle whose contraction tends to straighten a limb; the antagonist of a flexor. [NIH]

External radiation: Radiation therapy that uses a machine to aim high-energy rays at the cancer. Also called external-beam radiation. [NIH] Extracellular: Outside a cell or cells. [EU] Extracellular Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH] Extrapyramidal: Outside of the pyramidal tracts. [EU] Facial: Of or pertaining to the face. [EU] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Family Relations: Behavioral, psychological, and social relations among various members of the nuclear family and the extended family. [NIH] Fat: Total lipids including phospholipids. [NIH] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH]

Fatty acids: A major component of fats that are used by the body for energy and tissue development. [NIH] Feeding Behavior: Behavioral responses or sequences associated with eating including modes of feeding, rhythmic patterns of eating, and time intervals. [NIH] Fetal Blood: Blood of the fetus. Exchange of nutrients and waste between the fetal and maternal blood occurs via the placenta. The cord blood is blood contained in the umbilical vessels at the time of delivery. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibrin: A protein derived from fibrinogen in the presence of thrombin, which forms part of the blood clot. [NIH] Fissure: Any cleft or groove, normal or otherwise; especially a deep fold in the cerebral cortex which involves the entire thickness of the brain wall. [EU] Fluoxetine: The first highly specific serotonin uptake inhibitor. It is used as an antidepressant and often has a more acceptable side-effects profile than traditional antidepressants. [NIH] Fluphenazine: A phenothiazine used in the treatment of psychoses. Its properties and uses are generally similar to those of chlorpromazine. [NIH] Fluvoxamine: A selective serotonin reuptake inhibitor. It is effective in the treatment of depression, obsessive-compulsive disorders, anxiety, panic disorders, and alcohol amnestic disorders. [NIH] Folate: A B-complex vitamin that is being studied as a cancer prevention agent. Also called folic acid. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Folic Acid: N-(4-(((2-Amino-1,4-dihydro-4-oxo-6-pteridinyl)methyl)amino)benzoyl)-Lglutamic acid. A member of the vitamin B family that stimulates the hematopoietic system. It is present in the liver and kidney and is found in mushrooms, spinach, yeast, green leaves, and grasses. Folic acid is used in the treatment and prevention of folate deficiencies and

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megaloblastic anemia. [NIH] Food Preferences: The selection of one food over another. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Frontal Lobe: The anterior part of the cerebral hemisphere. [NIH] Functional magnetic resonance imaging: A noninvasive tool used to observe functioning in the brain or other organs by detecting changes in chemical composition, blood flow, or both. [NIH]

GABA: The most common inhibitory neurotransmitter in the central nervous system. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Ganglionic Blockers: Agents having as their major action the interruption of neural transmission at nicotinic receptors on postganglionic autonomic neurons. Because their actions are so broad, including blocking of sympathetic and parasympathetic systems, their therapeutic use has been largely supplanted by more specific drugs. They may still be used in the control of blood pressure in patients with acute dissecting aortic aneurysm and for the induction of hypotension in surgery. [NIH] Gap Junctions: Connections between cells which allow passage of small molecules and electric current. Gap junctions were first described anatomically as regions of close apposition between cells with a narrow (1-2 nm) gap between cell membranes. The variety in the properties of gap junctions is reflected in the number of connexins, the family of proteins which form the junctions. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gastric: Having to do with the stomach. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]

Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]

Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Genetic Code: The specifications for how information, stored in nucleic acid sequence (base sequence), is translated into protein sequence (amino acid sequence). The start, stop, and order of amino acids of a protein is specified by consecutive triplets of nucleotides called codons (codon). [NIH] Genetic testing: Analyzing DNA to look for a genetic alteration that may indicate an increased risk for developing a specific disease or disorder. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genomics: The systematic study of the complete DNA sequences (genome) of organisms. [NIH]

Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH]

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Germ Cells: The reproductive cells in multicellular organisms. [NIH] Gestation: The period of development of the young in viviparous animals, from the time of fertilization of the ovum until birth. [EU] Gestational: Psychosis attributable to or occurring during pregnancy. [NIH] Gestational Age: Age of the conceptus. In humans, this may be assessed by medical history, physical examination, early immunologic pregnancy tests, radiography, ultrasonography, and amniotic fluid analysis. [NIH] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Globus Pallidus: The representation of the phylogenetically oldest part of the corpus striatum called the paleostriatum. It forms the smaller, more medial part of the lentiform nucleus. [NIH] Glomerular: Pertaining to or of the nature of a glomerulus, especially a renal glomerulus. [EU]

Glomeruli: Plural of glomerulus. [NIH] Glomerulonephritis: Glomerular disease characterized by an inflammatory reaction, with leukocyte infiltration and cellular proliferation of the glomeruli, or that appears to be the result of immune glomerular injury. [NIH] Glomerulus: A tiny set of looping blood vessels in the nephron where blood is filtered in the kidney. [NIH] Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Glutamate: Excitatory neurotransmitter of the brain. [NIH] Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid (glutamate) is the most common excitatory neurotransmitter in the central nervous system. [NIH]

Gonad: A sex organ, such as an ovary or a testicle, which produces the gametes in most multicellular animals. [NIH] Gonadal: Pertaining to a gonad. [EU] Gout: Hereditary metabolic disorder characterized by recurrent acute arthritis, hyperuricemia and deposition of sodium urate in and around the joints, sometimes with formation of uric acid calculi. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] Grasses: A large family, Gramineae, of narrow-leaved herbaceous monocots. Many grasses produce highly allergenic pollens and are hosts to cattle parasites and toxic fungi. [NIH] Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] Guanylate Cyclase: An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and

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pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 4.6.1.2. [NIH] Hallucination: A sense perception without a source in the external world; a perception of an external stimulus object in the absence of such an object. [EU] Hallucinogen: A hallucination-producing drug, a category of drugs producing this effect. The user of a hallucinogenic drug is almost invariably aware that what he is seeing are hallucinations. [NIH] Haloperidol: Butyrophenone derivative. [NIH] Haplotypes: The genetic constitution of individuals with respect to one member of a pair of allelic genes, or sets of genes that are closely linked and tend to be inherited together such as those of the major histocompatibility complex. [NIH] Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response. [NIH] Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] Headache Disorders: Common conditions characterized by persistent or recurrent headaches. Headache syndrome classification systems may be based on etiology (e.g., vascular headache, post-traumatic headaches, etc.), temporal pattern (e.g., cluster headache, paroxysmal hemicrania, etc.), and precipitating factors (e.g., cough headache). [NIH] Heart attack: A seizure of weak or abnormal functioning of the heart. [NIH] Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH] Hemicrania: An ache or a pain in one side of the head, as in migraine. [NIH] Hemodynamics: The movements of the blood and the forces involved in systemic or regional blood circulation. [NIH] Hemolytic: A disease that affects the blood and blood vessels. It destroys red blood cells, cells that cause the blood to clot, and the lining of blood vessels. HUS is often caused by the Escherichia coli bacterium in contaminated food. People with HUS may develop acute renal failure. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hemostasis: The process which spontaneously arrests the flow of blood from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements, and the process of blood or plasma coagulation. [NIH]

Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Heritability: The proportion of observed variation in a particular trait that can be attributed to inherited genetic factors in contrast to environmental ones. [NIH] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance.

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[NIH]

Heterozygotes: Having unlike alleles at one or more corresponding loci on homologous chromosomes. [NIH] Hiccup: A spasm of the diaphragm that causes a sudden inhalation followed by rapid closure of the glottis which produces a sound. [NIH] Histamine: 1H-Imidazole-4-ethanamine. A depressor amine derived by enzymatic decarboxylation of histidine. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter. [NIH] Histidine: An essential amino acid important in a number of metabolic processes. It is required for the production of histamine. [NIH] Homogeneous: Consisting of or composed of similar elements or ingredients; of a uniform quality throughout. [EU] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Homozygotes: An individual having a homozygous gene pair. [NIH] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Host: Any animal that receives a transplanted graft. [NIH] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hyperlipidemia: An excess of lipids in the blood. [NIH] Hyperphagia: Ingestion of a greater than optimal quantity of food. [NIH] Hyperplasia: An increase in the number of cells in a tissue or organ, not due to tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in the number of cells. [NIH] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hypertrophy: General increase in bulk of a part or organ, not due to tumor formation, nor to an increase in the number of cells. [NIH] Hyperuricemia: A buildup of uric acid (a byproduct of metabolism) in the blood; a side effect of some anticancer drugs. [NIH] Hyperventilation: A pulmonary ventilation rate faster than is metabolically necessary for the exchange of gases. It is the result of an increased frequency of breathing, an increased tidal volume, or a combination of both. It causes an excess intake of oxygen and the blowing off of carbon dioxide. [NIH] Hypochondriasis: (DSM III-R) a mental disorder characterized by a preoccupation with

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bodily functions and the interpretation of normal sensations (such as heart beats, sweating, peristaltic action, and bowel movements) or minor abnormalities (such as a runny nose, minor aches and pains, or slightly swollen lymph nodes) as indications of highly disturbing problems needing medical attention. Negative results of diagnostic evaluations and reassurance by physicians only increase the patient's anxious concern about his health, and the patient continues to seek medical attention. Called also hypochondriacal neurosis. [EU] Hypokinesia: Slow or diminished movement of body musculature. It may be associated with basal ganglia diseases; mental disorders; prolonged inactivity due to illness; experimental protocols used to evaluate the physiologic effects of immobility; and other conditions. [NIH] Hypotension: Abnormally low blood pressure. [NIH] Hypotensive: Characterized by or causing diminished tension or pressure, as abnormally low blood pressure. [EU] Hypothalamus: Ventral part of the diencephalon extending from the region of the optic chiasm to the caudal border of the mammillary bodies and forming the inferior and lateral walls of the third ventricle. [NIH] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Idiopathic: Describes a disease of unknown cause. [NIH] Imipramine: The prototypical tricyclic antidepressant. It has been used in major depression, dysthymia, bipolar depression, attention-deficit disorders, agoraphobia, and panic disorders. It has less sedative effect than some other members of this therapeutic group. [NIH]

Immune Complex Diseases: Group of diseases mediated by the deposition of large soluble complexes of antigen and antibody with resultant damage to tissue. Besides serum sickness and the arthus reaction, evidence supports a pathogenic role for immune complexes in many other systemic immunologic diseases including glomerulonephritis, systemic lupus erythematosus and polyarteritis nodosa. [NIH] Immune function: Production and action of cells that fight disease or infection. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]

Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immunoglobulin: A protein that acts as an antibody. [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunology: The study of the body's immune system. [NIH] Immunotherapy: Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] Implantation: The insertion or grafting into the body of biological, living, inert, or radioactive material. [EU] Impotence: The inability to perform sexual intercourse. [NIH]

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Impotent: Unable to have an erection adequate for sexual intercourse. [NIH] Impulse Control Disorders: Disorders whose essential features are the failure to resist an impulse, drive, or temptation to perform an act that is harmful to the individual or to others. Individuals experience an increased sense of tension prior to the act and pleasure, gratification, or release of tension at the time of committing the act. [NIH] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In Situ Hybridization: A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes. [NIH] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incision: A cut made in the body during surgery. [NIH] Incontinence: Inability to control the flow of urine from the bladder (urinary incontinence) or the escape of stool from the rectum (fecal incontinence). [NIH] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Indomethacin: A non-steroidal anti-inflammatory agent (NSAID) that inhibits the enzyme cyclooxygenase necessary for the formation of prostaglandins and other autacoids. It also inhibits the motility of polymorphonuclear leukocytes. [NIH] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]

Infertility: The diminished or absent ability to conceive or produce an offspring while sterility is the complete inability to conceive or produce an offspring. [NIH] Infiltration: The diffusion or accumulation in a tissue or cells of substances not normal to it or in amounts of the normal. Also, the material so accumulated. [EU] Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Inotropic: Affecting the force or energy of muscular contractions. [EU] Inpatients: Persons admitted to health facilities which provide board and room, for the purpose of observation, care, diagnosis or treatment. [NIH] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH]

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Insomnia: Difficulty in going to sleep or getting enough sleep. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Internal Medicine: A medical specialty concerned with the diagnosis and treatment of diseases of the internal organ systems of adults. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intestines: The section of the alimentary canal from the stomach to the anus. It includes the large intestine and small intestine. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intracranial Hypertension: Increased pressure within the cranial vault. This may result from several conditions, including hydrocephalus; brain edema; intracranial masses; severe systemic hypertension; pseudotumor cerebri; and other disorders. [NIH] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]

Involuntary: Reaction occurring without intention or volition. [NIH] Ion Channels: Gated, ion-selective glycoproteins that traverse membranes. The stimulus for channel gating can be a membrane potential, drug, transmitter, cytoplasmic messenger, or a mechanical deformation. Ion channels which are integral parts of ionotropic neurotransmitter receptors are not included. [NIH] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Jealousy: An irrational reaction compounded of grief, loss of self-esteem, enmity against the rival and self criticism. [NIH] Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [NIH] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] Kinetic: Pertaining to or producing motion. [EU] Lactation: The period of the secretion of milk. [EU] Lag: The time elapsing between application of a stimulus and the resulting reaction. [NIH] Language Development: The gradual expansion in complexity and meaning of symbols and sounds as perceived and interpreted by the individual through a maturational and learning process. Stages in development include babbling, cooing, word imitation with cognition, and use of short sentences. [NIH] Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large intestine absorbs water from stool and changes it from a liquid to a solid form. The large intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called colon. [NIH] Larynx: An irregularly shaped, musculocartilaginous tubular structure, lined with mucous membrane, located at the top of the trachea and below the root of the tongue and the hyoid bone. It is the essential sphincter guarding the entrance into the trachea and functioning

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secondarily as the organ of voice. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Learning Disorders: Conditions characterized by a significant discrepancy between an individual's perceived level of intellect and their ability to acquire new language and other cognitive skills. These disorders may result from organic or psychological conditions. Relatively common subtypes include dyslexia, dyscalculia, and dysgraphia. [NIH] Lesion: An area of abnormal tissue change. [NIH] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Libido: The psychic drive or energy associated with sexual instinct in the broad sense (pleasure and love-object seeking). It may also connote the psychic energy associated with instincts in general that motivate behavior. [NIH] Library Services: Services offered to the library user. They include reference and circulation. [NIH]

Ligaments: Shiny, flexible bands of fibrous tissue connecting together articular extremities of bones. They are pliant, tough, and inextensile. [NIH] Ligands: A RNA simulation method developed by the MIT. [NIH] Limbic: Pertaining to a limbus, or margin; forming a border around. [EU] Limbic System: A set of forebrain structures common to all mammals that is defined functionally and anatomically. It is implicated in the higher integration of visceral, olfactory, and somatic information as well as homeostatic responses including fundamental survival behaviors (feeding, mating, emotion). For most authors, it includes the amygdala, epithalamus, gyrus cinguli, hippocampal formation (see hippocampus), hypothalamus, parahippocampal gyrus, septal nuclei, anterior nuclear group of thalamus, and portions of the basal ganglia. (Parent, Carpenter's Human Neuroanatomy, 9th ed, p744; NeuroNames, http://rprcsgi.rprc.washington.edu/neuronames/index.html (September 2, 1998)). [NIH] Linkage: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Linkage Disequilibrium: Nonrandom association of linked genes. This is the tendency of the alleles of two separate but already linked loci to be found together more frequently than would be expected by chance alone. [NIH] Lipid: Fat. [NIH] Lithium: An element in the alkali metals family. It has the atomic symbol Li, atomic number 3, and atomic weight 6.94. Salts of lithium are used in treating manic-depressive disorders. [NIH]

Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Lobe: A portion of an organ such as the liver, lung, breast, or brain. [NIH] Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Longitudinal study: Also referred to as a "cohort study" or "prospective study"; the analytic method of epidemiologic study in which subsets of a defined population can be identified

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who are, have been, or in the future may be exposed or not exposed, or exposed in different degrees, to a factor or factors hypothesized to influence the probability of occurrence of a given disease or other outcome. The main feature of this type of study is to observe large numbers of subjects over an extended time, with comparisons of incidence rates in groups that differ in exposure levels. [NIH] Long-Term Care: Care over an extended period, usually for a chronic condition or disability, requiring periodic, intermittent, or continuous care. [NIH] Loop: A wire usually of platinum bent at one end into a small loop (usually 4 mm inside diameter) and used in transferring microorganisms. [NIH] Lutein Cells: The cells of the corpus luteum which are derived from the granulosa cells and the theca cells of the Graafian follicle. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]

Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH] Lymphocyte Subsets: A classification of lymphocytes based on structurally or functionally different populations of cells. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques. [NIH] Magnetic Resonance Spectroscopy: Spectroscopic method of measuring the magnetic moment of elementary particles such as atomic nuclei, protons or electrons. It is employed in clinical applications such as NMR Tomography (magnetic resonance imaging). [NIH] Maintenance therapy: Treatment that is given to help a primary (original) treatment keep working. Maintenance therapy is often given to help keep cancer in remission. [NIH] Major Histocompatibility Complex: The genetic region which contains the loci of genes which determine the structure of the serologically defined (SD) and lymphocyte-defined (LD) transplantation antigens, genes which control the structure of the immune responseassociated (Ia) antigens, the immune response (Ir) genes which control the ability of an animal to respond immunologically to antigenic stimuli, and genes which determine the structure and/or level of the first four components of complement. [NIH] Malaise: A vague feeling of bodily discomfort. [EU] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Mania: Excitement of psychotic proportions manifested by mental and physical hyperactivity, disorganization of behaviour, and elevation of mood. [EU]

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Manic: Affected with mania. [EU] Manic-depressive psychosis: One of a group of psychotic reactions, fundamentally marked by severe mood swings and a tendency to remission and recurrence. [NIH] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] Meatus: A canal running from the internal auditory foramen through the petrous portion of the temporal bone. It gives passage to the facial and auditory nerves together with the auditory branch of the basilar artery and the internal auditory veins. [NIH] Mecamylamine: A nicotinic antagonist that is well absorbed from the gastrointestinal tract and crosses the blood-brain barrier. Mecamylamine has been used as a ganglionic blocker in treating hypertension, but, like most ganglionic blockers, is more often used now as a research tool. [NIH] Medial: Lying near the midsaggital plane of the body; opposed to lateral. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] Medicament: A medicinal substance or agent. [EU] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Megaloblastic: A large abnormal red blood cell appearing in the blood in pernicious anaemia. [EU] Meiosis: A special method of cell division, occurring in maturation of the germ cells, by means of which each daughter nucleus receives half the number of chromosomes characteristic of the somatic cells of the species. [NIH] Melanin: The substance that gives the skin its color. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] Memory Disorders: Disturbances in registering an impression, in the retention of an acquired impression, or in the recall of an impression. Memory impairments are associated with dementia; craniocerebraltrauma; encephalitis; alcoholism (see also alcohol amnestic disorder); schizophrenia; and other conditions. [NIH] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Menstrual Cycle: The period of the regularly recurring physiologic changes in the endometrium occurring during the reproductive period in human females and some primates and culminating in partial sloughing of the endometrium (menstruation). [NIH] Menstruation: The normal physiologic discharge through the vagina of blood and mucosal tissues from the nonpregnant uterus. [NIH] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH]

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Mental Health: The state wherein the person is well adjusted. [NIH] Mentors: Senior professionals who provide guidance, direction and support to those persons desirous of improvement in academic positions, administrative positions or other career development situations. [NIH] Mesolimbic: Inner brain region governing emotion and drives. [NIH] Meta-Analysis: A quantitative method of combining the results of independent studies (usually drawn from the published literature) and synthesizing summaries and conclusions which may be used to evaluate therapeutic effectiveness, plan new studies, etc., with application chiefly in the areas of research and medicine. [NIH] Metabolic disorder: A condition in which normal metabolic processes are disrupted, usually because of a missing enzyme. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Methanol: A colorless, flammable liquid used in the manufacture of formaldehyde and acetic acid, in chemical synthesis, antifreeze, and as a solvent. Ingestion of methanol is toxic and may cause blindness. [NIH] Methyltransferase: A drug-metabolizing enzyme. [NIH] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Microdialysis: A technique for measuring extracellular concentrations of substances in tissues, usually in vivo, by means of a small probe equipped with a semipermeable membrane. Substances may also be introduced into the extracellular space through the membrane. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH] Middle Cerebral Artery: The largest and most complex of the cerebral arteries. Branches of the middle cerebral artery supply the insular region, motor and premotor areas, and large regions of the association cortex. [NIH] Mode of Transmission: Hepatitis A [NIH] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Modulator: A specific inductor that brings out characteristics peculiar to a definite region. [EU]

Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecular Structure: The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds. [NIH] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two

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hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monoamine: Enzyme that breaks down dopamine in the astrocytes and microglia. [NIH] Monoamine Oxidase: An enzyme that catalyzes the oxidative deamination of naturally occurring monoamines. It is a flavin-containing enzyme that is localized in mitochondrial membranes, whether in nerve terminals, the liver, or other organs. Monoamine oxidase is important in regulating the metabolic degradation of catecholamines and serotonin in neural or target tissues. Hepatic monoamine oxidase has a crucial defensive role in inactivating circulating monoamines or those, such as tyramine, that originate in the gut and are absorbed into the portal circulation. (From Goodman and Gilman's, The Pharmacological Basis of Therapeutics, 8th ed, p415) EC 1.4.3.4. [NIH] Monotherapy: A therapy which uses only one drug. [EU] Mood Disorders: Those disorders that have a disturbance in mood as their predominant feature. [NIH] Morphine: The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle. [NIH] Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [NIH] Motility: The ability to move spontaneously. [EU] Movement Disorders: Syndromes which feature dyskinesias as a cardinal manifestation of the disease process. Included in this category are degenerative, hereditary, post-infectious, medication-induced, post-inflammatory, and post-traumatic conditions. [NIH] Mucosa: A mucous membrane, or tunica mucosa. [EU] Multicenter Studies: Controlled studies which are planned and carried out by several cooperating institutions to assess certain variables and outcomes in specific patient populations, for example, a multicenter study of congenital anomalies in children. [NIH] Multicenter study: A clinical trial that is carried out at more than one medical institution. [NIH]

Mutilation: Injuries to the body. [NIH] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Naive: Used to describe an individual who has never taken a certain drug or class of drugs (e. g., AZT-naive, antiretroviral-naive), or to refer to an undifferentiated immune system cell. [NIH] Naloxone: A specific opiate antagonist that has no agonist activity. It is a competitive antagonist at mu, delta, and kappa opioid receptors. [NIH] Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. [NIH] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis,

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prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] Need: A state of tension or dissatisfaction felt by an individual that impels him to action toward a goal he believes will satisfy the impulse. [NIH] Neonatal: Pertaining to the first four weeks after birth. [EU] Neostriatum: The phylogenetically newer part of the corpus striatum consisting of the caudate nucleus and putamen. It is often called simply the striatum. [NIH] Nephritis: Inflammation of the kidney; a focal or diffuse proliferative or destructive process which may involve the glomerulus, tubule, or interstitial renal tissue. [EU] Nephrogenic: Constant thirst and frequent urination because the kidney tubules cannot respond to antidiuretic hormone. The result is an increase in urine formation and excessive urine flow. [NIH] Nephron: A tiny part of the kidneys. Each kidney is made up of about 1 million nephrons, which are the working units of the kidneys, removing wastes and extra fluids from the blood. [NIH] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Networks: Pertaining to a nerve or to the nerves, a meshlike structure of interlocking fibers or strands. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neural Pathways: Neural tracts connecting one part of the nervous system with another. [NIH]

Neuroanatomy: Study of the anatomy of the nervous system as a specialty or discipline. [NIH]

Neurodegenerative Diseases: Hereditary and sporadic conditions which are characterized by progressive nervous system dysfunction. These disorders are often associated with atrophy of the affected central or peripheral nervous system structures. [NIH] Neuroleptic: A term coined to refer to the effects on cognition and behaviour of antipsychotic drugs, which produce a state of apathy, lack of initiative, and limited range of emotion and in psychotic patients cause a reduction in confusion and agitation and normalization of psychomotor activity. [EU] Neurologic: Having to do with nerves or the nervous system. [NIH] Neurology: A medical specialty concerned with the study of the structures, functions, and diseases of the nervous system. [NIH] Neuromuscular: Pertaining to muscles and nerves. [EU] Neuromuscular Junction: The synapse between a neuron and a muscle. [NIH] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH]

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Neuropeptide: A member of a class of protein-like molecules made in the brain. Neuropeptides consist of short chains of amino acids, with some functioning as neurotransmitters and some functioning as hormones. [NIH] Neuropharmacology: The branch of pharmacology dealing especially with the action of drugs upon various parts of the nervous system. [NIH] Neuropsychology: A branch of psychology which investigates the correlation between experience or behavior and the basic neurophysiological processes. The term neuropsychology stresses the dominant role of the nervous system. It is a more narrowly defined field than physiological psychology or psychophysiology. [NIH] Neurosis: Functional derangement due to disorders of the nervous system which does not affect the psychic personality of the patient. [NIH] Neurosurgery: A surgical specialty concerned with the treatment of diseases and disorders of the brain, spinal cord, and peripheral and sympathetic nervous system. [NIH] Neurotic: 1. Pertaining to or characterized by neurosis. 2. A person affected with a neurosis. [EU]

Neurotransmitters: Endogenous signaling molecules that alter the behavior of neurons or effector cells. Neurotransmitter is used here in its most general sense, including not only messengers that act directly to regulate ion channels, but also those that act through second messenger systems, and those that act at a distance from their site of release. Included are neuromodulators, neuroregulators, neuromediators, and neurohumors, whether or not acting at synapses. [NIH] Niacin: Water-soluble vitamin of the B complex occurring in various animal and plant tissues. Required by the body for the formation of coenzymes NAD and NADP. Has pellagra-curative, vasodilating, and antilipemic properties. [NIH] Nicotine: Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke. [NIH] Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells. It is synthesized from arginine by a complex reaction, catalyzed by nitric oxide synthase. Nitric oxide is endothelium-derived relaxing factor. It is released by the vascular endothelium and mediates the relaxation induced by some vasodilators such as acetylcholine and bradykinin. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic guanylate cyclase and thus elevates intracellular levels of cyclic GMP. [NIH]

Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight 14. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. [NIH] Nocturia: Excessive urination at night. [EU] Nonverbal Communication: Transmission of emotions, ideas, and attitudes between individuals in ways other than the spoken language. [NIH] Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic. [NIH] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a

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mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclear Family: A family composed of spouses and their children. [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Observational study: An epidemiologic study that does not involve any intervention, experimental or otherwise. Such a study may be one in which nature is allowed to take its course, with changes in one characteristic being studied in relation to changes in other characteristics. Analytical epidemiologic methods, such as case-control and cohort study designs, are properly called observational epidemiology because the investigator is observing without intervention other than to record, classify, count, and statistically analyze results. [NIH] Obsession: A recurrent, persistent thought, image, or impulse that is unwanted and distressing (ego-dystonic) and comes involuntarily to mind despite attempts to ignore or suppress it. Common obsessions involve thoughts of violence, contamination, and selfdoubt. [EU] Obsessional: Neurosis characterized by the repetitive intrusion into the mind, against volition, of ideas, numinations and phobias, often associated with compulsive actions. [NIH] Odds Ratio: The ratio of two odds. The exposure-odds ratio for case control data is the ratio of the odds in favor of exposure among cases to the odds in favor of exposure among noncases. The disease-odds ratio for a cohort or cross section is the ratio of the odds in favor of disease among the exposed to the odds in favor of disease among the unexposed. The prevalence-odds ratio refers to an odds ratio derived cross-sectionally from studies of prevalent cases. [NIH] Oligohydramnios: Presence of less than 300 ml of amniotic fluid at term. Principal causes include malformations of fetal urinary tracts, intra-uterine growth retardation, high maternal blood pressure, nicotine poisoning, and prolonged pregnancy. [NIH] Ondansetron: A competitive serotonin type 3 receptor antagonist. It is effective in the treatment of nausea and vomiting caused by cytotoxic chemotherapy drugs, including cisplatin, and it has reported anxiolytic and neuroleptic properties. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Optic Chiasm: The X-shaped structure formed by the meeting of the two optic nerves. At the optic chiasm the fibers from the medial part of each retina cross to project to the other side of the brain while the lateral retinal fibers continue on the same side. As a result each half of the brain receives information about the contralateral visual field from both eyes. [NIH]

Orbit: One of the two cavities in the skull which contains an eyeball. Each eye is located in a bony socket or orbit. [NIH] Orbital: Pertaining to the orbit (= the bony cavity that contains the eyeball). [EU] Orderly: A male hospital attendant. [NIH] Orgasm: The crisis of sexual excitement in either humans or animals. [NIH]

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Orthostatic: Pertaining to or caused by standing erect. [EU] Osteoarthritis: A progressive, degenerative joint disease, the most common form of arthritis, especially in older persons. The disease is thought to result not from the aging process but from biochemical changes and biomechanical stresses affecting articular cartilage. In the foreign literature it is often called osteoarthrosis deformans. [NIH] Outpatient: A patient who is not an inmate of a hospital but receives diagnosis or treatment in a clinic or dispensary connected with the hospital. [NIH] Ovum: A female germ cell extruded from the ovary at ovulation. [NIH] Oxytocin: A nonapeptide posterior pituitary hormone that causes uterine contractions and stimulates lactation. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Panic: A state of extreme acute, intense anxiety and unreasoning fear accompanied by disorganization of personality function. [NIH] Panic Disorder: A type of anxiety disorder characterized by unexpected panic attacks that last minutes or, rarely, hours. Panic attacks begin with intense apprehension, fear or terror and, often, a feeling of impending doom. Symptoms experienced during a panic attack include dyspnea or sensations of being smothered; dizziness, loss of balance or faintness; choking sensations; palpitations or accelerated heart rate; shakiness; sweating; nausea or other form of abdominal distress; depersonalization or derealization; paresthesias; hot flashes or chills; chest discomfort or pain; fear of dying and fear of not being in control of oneself or going crazy. Agoraphobia may also develop. Similar to other anxiety disorders, it may be inherited as an autosomal dominant trait. [NIH] Paranoia: A psychotic disorder marked by persistent delusions of persecution or delusional jealousy and behaviour like that of the paranoid personality, such as suspiciousness, mistrust, and combativeness. It differs from paranoid schizophrenia, in which hallucinations or formal thought disorder are present, in that the delusions are logically consistent and that there are no other psychotic features. The designation in DSM III-R is delusional (paranoid) disorders, with five types : persecutory, jealous, erotomanic, somatic, and grandiose. [EU] Paresthesias: Abnormal touch sensations, such as burning or prickling, that occur without an outside stimulus. [NIH] Parkinsonism: A group of neurological disorders characterized by hypokinesia, tremor, and muscular rigidity. [EU] Paroxetine: A serotonin uptake inhibitor that is effective in the treatment of depression. [NIH]

Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] Partial remission: The shrinking, but not complete disappearance, of a tumor in response to therapy. Also called partial response. [NIH] Partial response: A decrease in the size of a tumor, or in the extent of cancer in the body, in response to treatment. [NIH] Parturition: The act or process of given birth to a child. [EU] Pathogen: Any disease-producing microorganism. [EU] Pathogenesis: The cellular events and reactions that occur in the development of disease.

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[NIH]

Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologies: The study of abnormality, especially the study of diseases. [NIH] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Patient Education: The teaching or training of patients concerning their own health needs. [NIH]

Pedigree: A record of one's ancestors, offspring, siblings, and their offspring that may be used to determine the pattern of certain genes or disease inheritance within a family. [NIH] Penicillin: An antibiotic drug used to treat infection. [NIH] Penis: The external reproductive organ of males. It is composed of a mass of erectile tissue enclosed in three cylindrical fibrous compartments. Two of the three compartments, the corpus cavernosa, are placed side-by-side along the upper part of the organ. The third compartment below, the corpus spongiosum, houses the urethra. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Perception: The ability quickly and accurately to recognize similarities and differences among presented objects, whether these be pairs of words, pairs of number series, or multiple sets of these or other symbols such as geometric figures. [NIH] Pergolide: A long-acting dopamine agonist which is effective in the treatment of Parkinson's disease and hyperprolactinemia. It has also been observed to have antihypertensive effects. [NIH]

Perinatal: Pertaining to or occurring in the period shortly before and after birth; variously defined as beginning with completion of the twentieth to twenty-eighth week of gestation and ending 7 to 28 days after birth. [EU] Periodicity: The tendency of a phenomenon to recur at regular intervals; in biological systems, the recurrence of certain activities (including hormonal, cellular, neural) may be annual, seasonal, monthly, daily, or more frequently (ultradian). [NIH] Pernicious: Tending to a fatal issue. [EU] Personality Disorders: A major deviation from normal patterns of behavior. [NIH] PH: The symbol relating the hydrogen ion (H+) concentration or activity of a solution to that of a given standard solution. Numerically the pH is approximately equal to the negative logarithm of H+ concentration expressed in molarity. pH 7 is neutral; above it alkalinity increases and below it acidity increases. [EU] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Pharmacotherapy: A regimen of using appetite suppressant medications to manage obesity by decreasing appetite or increasing the feeling of satiety. These medications decrease appetite by increasing serotonin or catecholamine—two brain chemicals that affect mood and appetite. [NIH] Pharyngitis: Inflammation of the throat. [NIH] Pharynx: The hollow tube about 5 inches long that starts behind the nose and ends at the top of the trachea (windpipe) and esophagus (the tube that goes to the stomach). [NIH] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH]

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Phenyl: Ingredient used in cold and flu remedies. [NIH] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Phobia: A persistent, irrational, intense fear of a specific object, activity, or situation (the phobic stimulus), fear that is recognized as being excessive or unreasonable by the individual himself. When a phobia is a significant source of distress or interferes with social functioning, it is considered a mental disorder; phobic disorder (or neurosis). In DSM III phobic disorders are subclassified as agoraphobia, social phobias, and simple phobias. Used as a word termination denoting irrational fear of or aversion to the subject indicated by the stem to which it is affixed. [EU] Phobic Disorders: Anxiety disorders in which the essential feature is persistent and irrational fear of a specific object, activity, or situation that the individual feels compelled to avoid. The individual recognizes the fear as excessive or unreasonable. [NIH] Phosphodiesterase: Effector enzyme that regulates the levels of a second messenger, the cyclic GMP. [NIH] Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-. [NIH] Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides; glycerophospholipids) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Photocoagulation: Using a special strong beam of light (laser) to seal off bleeding blood vessels such as in the eye. The laser can also burn away blood vessels that should not have grown in the eye. This is the main treatment for diabetic retinopathy. [NIH] Phototherapy: Treatment of disease by exposure to light, especially by variously concentrated light rays or specific wavelengths. [NIH] Physical Examination: Systematic and thorough inspection of the patient for physical signs of disease or abnormality. [NIH] Physician Assistants: Persons academically trained, licensed, or credentialed to provide medical care under the supervision of a physician. The concept does not include nurses, but does include orthopedic assistants, surgeon's assistants, and assistants to other specialists. [NIH]

Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]

Physiology: The science that deals with the life processes and functions of organismus, their cells, tissues, and organs. [NIH] Pilot study: The initial study examining a new method or treatment. [NIH] Placebos: Any dummy medication or treatment. Although placebos originally were medicinal preparations having no specific pharmacological activity against a targeted condition, the concept has been extended to include treatments or procedures, especially those administered to control groups in clinical trials in order to provide baseline measurements for the experimental protocol. [NIH]

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Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plaque: A clear zone in a bacterial culture grown on an agar plate caused by localized destruction of bacterial cells by a bacteriophage. The concentration of infective virus in a fluid can be estimated by applying the fluid to a culture and counting the number of. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasma Exchange: Removal of plasma and replacement with various fluids, e.g., fresh frozen plasma, plasma protein fractions (PPF), albumin preparations, dextran solutions, saline. Used in treatment of autoimmune diseases, immune complex diseases, diseases of excess plasma factors, and other conditions. [NIH] Plasma protein: One of the hundreds of different proteins present in blood plasma, including carrier proteins ( such albumin, transferrin, and haptoglobin), fibrinogen and other coagulation factors, complement components, immunoglobulins, enzyme inhibitors, precursors of substances such as angiotension and bradykinin, and many other types of proteins. [EU] Plasmapheresis: Procedure whereby plasma is separated and extracted from anticoagulated whole blood and the red cells retransfused to the donor. Plasmapheresis is also employed for therapeutic use. [NIH] Plasmin: A product of the lysis of plasminogen (profibrinolysin) by plasminogen activators. It is composed of two polypeptide chains, light (B) and heavy (A), with a molecular weight of 75,000. It is the major proteolytic enzyme involved in blood clot retraction or the lysis of fibrin and quickly inactivated by antiplasmins. EC 3.4.21.7. [NIH] Plasminogen: Precursor of fibrinolysin (plasmin). It is a single-chain beta-globulin of molecular weight 80-90,000 found mostly in association with fibrinogen in plasma; plasminogen activators change it to fibrinolysin. It is used in wound debriding and has been investigated as a thrombolytic agent. [NIH] Plasminogen Activators: A heterogeneous group of proteolytic enzymes that convert plasminogen to plasmin. They are concentrated in the lysosomes of most cells and in the vascular endothelium, particularly in the vessels of the microcirculation. EC 3.4.21.-. [NIH] Platelet Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Platinum: Platinum. A heavy, soft, whitish metal, resembling tin, atomic number 78, atomic weight 195.09, symbol Pt. (From Dorland, 28th ed) It is used in manufacturing equipment for laboratory and industrial use. It occurs as a black powder (platinum black) and as a spongy substance (spongy platinum) and may have been known in Pliny's time as "alutiae". [NIH]

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Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Polymorphism: The occurrence together of two or more distinct forms in the same population. [NIH] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Post-synaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Post-traumatic: Occurring as a result of or after injury. [EU] Post-traumatic stress disorder: A psychological disorder that develops in some individuals after a major traumatic experience such as war, rape, domestic violence, or accident. [NIH] Potentiates: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH] Practicability: A non-standard characteristic of an analytical procedure. It is dependent on the scope of the method and is determined by requirements such as sample throughout and costs. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Prefrontal Cortex: The rostral part of the frontal lobe, bounded by the inferior precentral fissure in humans, which receives projection fibers from the mediodorsal nucleus of the thalamus. The prefrontal cortex receives afferent fibers from numerous structures of the diencephalon, mesencephalon, and limbic system as well as cortical afferents of visual, auditory, and somatic origin. [NIH] Pregnancy Tests: Tests to determine whether or not an individual is pregnant. [NIH] Premenstrual: Occurring before menstruation. [EU] Premenstrual Syndrome: A syndrome occurring most often during the last week of the menstrual cycle and ending soon after the onset of menses. Some of the symptoms are emotional instability, insomnia, headache, nausea, vomiting, abdominal distension, and painful breasts. [NIH] Prenatal: Existing or occurring before birth, with reference to the fetus. [EU] Presynaptic: Situated proximal to a synapse, or occurring before the synapse is crossed. [EU] Presynaptic Terminals: The distal terminations of axons which are specialized for the

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release of neurotransmitters. Also included are varicosities along the course of axons which have similar specializations and also release transmitters. Presynaptic terminals in both the central and peripheral nervous systems are included. [NIH] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Probe: An instrument used in exploring cavities, or in the detection and dilatation of strictures, or in demonstrating the potency of channels; an elongated instrument for exploring or sounding body cavities. [NIH] Prodrug: A substance that gives rise to a pharmacologically active metabolite, although not itself active (i. e. an inactive precursor). [NIH] Progesterone: Pregn-4-ene-3,20-dione. The principal progestational hormone of the body, secreted by the corpus luteum, adrenal cortex, and placenta. Its chief function is to prepare the uterus for the reception and development of the fertilized ovum. It acts as an antiovulatory agent when administered on days 5-25 of the menstrual cycle. [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Projection: A defense mechanism, operating unconsciously, whereby that which is emotionally unacceptable in the self is rejected and attributed (projected) to others. [NIH] Prolactin: Pituitary lactogenic hormone. A polypeptide hormone with a molecular weight of about 23,000. It is essential in the induction of lactation in mammals at parturition and is synergistic with estrogen. The hormone also brings about the release of progesterone from lutein cells, which renders the uterine mucosa suited for the embedding of the ovum should fertilization occur. [NIH] Proline: A non-essential amino acid that is synthesized from glutamic acid. It is an essential component of collagen and is important for proper functioning of joints and tendons. [NIH] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] Prophase: The first phase of cell division, in which the chromosomes become visible, the nucleus starts to lose its identity, the spindle appears, and the centrioles migrate toward opposite poles. [NIH] Prospective Studies: Observation of a population for a sufficient number of persons over a sufficient number of years to generate incidence or mortality rates subsequent to the selection of the study group. [NIH] Prospective study: An epidemiologic study in which a group of individuals (a cohort), all free of a particular disease and varying in their exposure to a possible risk factor, is followed over a specific amount of time to determine the incidence rates of the disease in the exposed and unexposed groups. [NIH] Prostaglandin: Any of a group of components derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway that are extremely potent mediators of a diverse group of physiologic processes. The abbreviation for prostaglandin is PG; specific compounds are designated by adding one of the letters A through I to indicate the type of substituents found on the hydrocarbon skeleton and a subscript (1, 2 or 3) to indicate the number of double bonds in the hydrocarbon skeleton e.g., PGE2. The predominant naturally occurring prostaglandins all have two double bonds and are synthesized from arachidonic acid (5,8,11,14-eicosatetraenoic acid) by the pathway shown in the illustration. The 1 series and 3 series are produced by the same pathway with fatty acids

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having one fewer double bond (8,11,14-eicosatrienoic acid or one more double bond (5,8,11,14,17-eicosapentaenoic acid) than arachidonic acid. The subscript a or ß indicates the configuration at C-9 (a denotes a substituent below the plane of the ring, ß, above the plane). The naturally occurring PGF's have the a configuration, e.g., PGF2a. All of the prostaglandins act by binding to specific cell-surface receptors causing an increase in the level of the intracellular second messenger cyclic AMP (and in some cases cyclic GMP also). The effect produced by the cyclic AMP increase depends on the specific cell type. In some cases there is also a positive feedback effect. Increased cyclic AMP increases prostaglandin synthesis leading to further increases in cyclic AMP. [EU] Prostaglandins A: (13E,15S)-15-Hydroxy-9-oxoprosta-10,13-dien-1-oic acid (PGA(1)); (5Z,13E,15S)-15-hydroxy-9-oxoprosta-5,10,13-trien-1-oic acid (PGA(2)); (5Z,13E,15S,17Z)-15hydroxy-9-oxoprosta-5,10,13,17-tetraen-1-oic acid (PGA(3)). A group of naturally occurring secondary prostaglandins derived from PGE. PGA(1) and PGA(2) as well as their 19hydroxy derivatives are found in many organs and tissues. [NIH] Protective Agents: Synthetic or natural substances which are given to prevent a disease or disorder or are used in the process of treating a disease or injury due to a poisonous agent. [NIH]

Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific proteinbinding measures are often used as assays in diagnostic assessments. [NIH] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Pruritic: Pertaining to or characterized by pruritus. [EU] Psoriasis: A common genetically determined, chronic, inflammatory skin disease characterized by rounded erythematous, dry, scaling patches. The lesions have a predilection for nails, scalp, genitalia, extensor surfaces, and the lumbosacral region. Accelerated epidermopoiesis is considered to be the fundamental pathologic feature in psoriasis. [NIH] Psychiatric: Pertaining to or within the purview of psychiatry. [EU] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH]

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Psychic: Pertaining to the psyche or to the mind; mental. [EU] Psychogenic: Produced or caused by psychic or mental factors rather than organic factors. [EU]

Psychology: The science dealing with the study of mental processes and behavior in man and animals. [NIH] Psychomotor: Pertaining to motor effects of cerebral or psychic activity. [EU] Psychopathology: The study of significant causes and processes in the development of mental illness. [NIH] Psychophysiology: The study of the physiological basis of human and animal behavior. [NIH]

Psychosis: A mental disorder characterized by gross impairment in reality testing as evidenced by delusions, hallucinations, markedly incoherent speech, or disorganized and agitated behaviour without apparent awareness on the part of the patient of the incomprehensibility of his behaviour; the term is also used in a more general sense to refer to mental disorders in which mental functioning is sufficiently impaired as to interfere grossly with the patient's capacity to meet the ordinary demands of life. Historically, the term has been applied to many conditions, e.g. manic-depressive psychosis, that were first described in psychotic patients, although many patients with the disorder are not judged psychotic. [EU] Psychotherapy: A generic term for the treatment of mental illness or emotional disturbances primarily by verbal or nonverbal communication. [NIH] Psychotomimetic: Psychosis miming. [NIH] Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [NIH]

Pulmonary: Relating to the lungs. [NIH] Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [NIH] Pulmonary hypertension: Abnormally high blood pressure in the arteries of the lungs. [NIH] Pulmonary Ventilation: The total volume of gas per minute inspired or expired measured in liters per minute. [NIH] Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]

Putamen: The largest and most lateral of the basal ganglia lying between the lateral medullary lamina of the globus pallidus and the external capsule. It is part of the neostriatum and forms part of the lentiform nucleus along with the globus pallidus. [NIH] Pyrogenic: Inducing fever. [EU] Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment. [NIH]

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Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radiation therapy: The use of high-energy radiation from x-rays, gamma rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body in the area near cancer cells (internal radiation therapy, implant radiation, or brachytherapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Also called radiotherapy. [NIH] Radioactive: Giving off radiation. [NIH] Radiography: Examination of any part of the body for diagnostic purposes by means of roentgen rays, recording the image on a sensitized surface (such as photographic film). [NIH] Radiolabeled: Any compound that has been joined with a radioactive substance. [NIH] Rage: Fury; violent, intense anger. [NIH] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] Randomized clinical trial: A study in which the participants are assigned by chance to separate groups that compare different treatments; neither the researchers nor the participants can choose which group. Using chance to assign people to groups means that the groups will be similar and that the treatments they receive can be compared objectively. At the time of the trial, it is not known which treatment is best. It is the patient's choice to be in a randomized trial. [NIH] Rape: Unlawful sexual intercourse without consent of the victim. [NIH] Raphe Nuclei: Collections of small neurons centrally scattered among many fibers from the level of the trochlear nucleus in the midbrain to the hypoglossal area in the medulla oblongata. [NIH] Reabsorption: 1. The act or process of absorbing again, as the selective absorption by the kidneys of substances (glucose, proteins, sodium, etc.) already secreted into the renal tubules, and their return to the circulating blood. 2. Resorption. [EU] Reality Testing: The individual's objective evaluation of the external world and the ability to differentiate adequately between it and the internal world; considered to be a primary ego function. [NIH] Reassurance: A procedure in psychotherapy that seeks to give the client confidence in a favorable outcome. It makes use of suggestion, of the prestige of the therapist. [NIH] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Receptors, Serotonin: Cell-surface proteins that bind serotonin and trigger intracellular changes which influence the behavior of cells. Several types of serotonin receptors have been recognized which differ in their pharmacology, molecular biology, and mode of action. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Rectum: The last 8 to 10 inches of the large intestine. [NIH]

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Recur: To occur again. Recurrence is the return of cancer, at the same site as the original (primary) tumor or in another location, after the tumor had disappeared. [NIH] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Red blood cells: RBCs. Cells that carry oxygen to all parts of the body. Also called erythrocytes. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Reflex: An involuntary movement or exercise of function in a part, excited in response to a stimulus applied to the periphery and transmitted to the brain or spinal cord. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Refractory: Not readily yielding to treatment. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Relapse: The return of signs and symptoms of cancer after a period of improvement. [NIH] Relative risk: The ratio of the incidence rate of a disease among individuals exposed to a specific risk factor to the incidence rate among unexposed individuals; synonymous with risk ratio. Alternatively, the ratio of the cumulative incidence rate in the exposed to the cumulative incidence rate in the unexposed (cumulative incidence ratio). The term relative risk has also been used synonymously with odds ratio. This is because the odds ratio and relative risk approach each other if the disease is rare ( 5 percent of population) and the number of subjects is large. [NIH] Relaxation Techniques: The use of muscular relaxation techniques in treatment. [NIH] Reliability: Used technically, in a statistical sense, of consistency of a test with itself, i. e. the extent to which we can assume that it will yield the same result if repeated a second time. [NIH]

Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] Research Design: A plan for collecting and utilizing data so that desired information can be obtained with sufficient precision or so that an hypothesis can be tested properly. [NIH] Research Support: Financial support of research activities. [NIH] Reserpine: An alkaloid found in the roots of Rauwolfia serpentina and R. vomitoria. Reserpine inhibits the uptake of norepinephrine into storage vesicles resulting in depletion of catecholamines and serotonin from central and peripheral axon terminals. It has been used as an antihypertensive and an antipsychotic as well as a research tool, but its adverse effects limit its clinical use. [NIH] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Response rate: The percentage of patients whose cancer shrinks or disappears after treatment. [NIH] Reticulata: Part of substantia nigra. [NIH] Retrospective: Looking back at events that have already taken place. [NIH]

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Ribosome: A granule of protein and RNA, synthesized in the nucleolus and found in the cytoplasm of cells. Ribosomes are the main sites of protein synthesis. Messenger RNA attaches to them and there receives molecules of transfer RNA bearing amino acids. [NIH] Rigidity: Stiffness or inflexibility, chiefly that which is abnormal or morbid; rigor. [EU] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Risperidone: A selective blocker of dopamine D2 and serotonin-5-HT-2 receptors that acts as an atypical antipsychotic agent. It has been shown to improve both positive and negative symptoms in the treatment of schizophrenia. [NIH] Saline: A solution of salt and water. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Saponins: Sapogenin glycosides. A type of glycoside widely distributed in plants. Each consists of a sapogenin as the aglycon moiety, and a sugar. The sapogenin may be a steroid or a triterpene and the sugar may be glucose, galactose, a pentose, or a methylpentose. Sapogenins are poisonous towards the lower forms of life and are powerful hemolytics when injected into the blood stream able to dissolve red blood cells at even extreme dilutions. [NIH] Schizoid: Having qualities resembling those found in greater degree in schizophrenics; a person of schizoid personality. [NIH] Schizophrenia: A mental disorder characterized by a special type of disintegration of the personality. [NIH] Schizotypal Personality Disorder: A personality disorder in which there are oddities of thought (magical thinking, paranoid ideation, suspiciousness), perception (illusions, depersonalization), speech (digressive, vague, overelaborate), and behavior (inappropriate affect in social interactions, frequently social isolation) that are not severe enough to characterize schizophrenia. [NIH] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Seasonal Affective Disorder: A syndrome characterized by depressions that recur annually at the same time each year, usually during the winter months. Other symptoms include anxiety, irritability, decreased energy, increased appetite (carbohydrate cravings), increased duration of sleep, and weight gain. SAD (seasonal affective disorder) can be treated by daily exposure to bright artificial lights (phototherapy), during the season of recurrence. [NIH] Second Messenger Systems: Systems in which an intracellular signal is generated in response to an intercellular primary messenger such as a hormone or neurotransmitter. They are intermediate signals in cellular processes such as metabolism, secretion, contraction, phototransduction, and cell growth. Examples of second messenger systems are the adenyl cyclase-cyclic AMP system, the phosphatidylinositol diphosphate-inositol triphosphate system, and the cyclic GMP system. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Secretory: Secreting; relating to or influencing secretion or the secretions. [NIH] Sedative: 1. Allaying activity and excitement. 2. An agent that allays excitement. [EU]

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Segregation: The separation in meiotic cell division of homologous chromosome pairs and their contained allelomorphic gene pairs. [NIH] Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as epilepsy or "seizure disorder." [NIH] Semen: The thick, yellowish-white, viscid fluid secretion of male reproductive organs discharged upon ejaculation. In addition to reproductive organ secretions, it contains spermatozoa and their nutrient plasma. [NIH] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (receptors, serotonin) explain the broad physiological actions and distribution of this biochemical mediator. [NIH] Serotonin Agonists: Agents that have an affinity for serotonin receptors and are able to mimic the effects of serotonin by stimulating the physiologic activity at the cell receptors. These compounds are used as antidepressants, anxiolytics, and in the treatment of migraine. [NIH]

Serotonin Antagonists: Drugs that bind to but do not activate serotonin receptors, thereby blocking the actions of serotonin or serotonin agonists. [NIH] Sertraline: A selective serotonin uptake inhibitor that is used in the treatment of depression. [NIH]

Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Sex Characteristics: Those characteristics that distinguish one sex from the other. The primary sex characteristics are the ovaries and testes and their related hormones. Secondary sex characteristics are those which are masculine or feminine but not directly related to reproduction. [NIH] Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]

Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal

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transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. [NIH] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Sleep apnea: A serious, potentially life-threatening breathing disorder characterized by repeated cessation of breathing due to either collapse of the upper airway during sleep or absence of respiratory effort. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]

Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Social Problems: Situations affecting a significant number of people, that are believed to be sources of difficulty or threaten the stability of the community, and that require programs of amelioration. [NIH] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] Soma: The body as distinct from the mind; all the body tissue except the germ cells; all the axial body. [NIH] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Spasticity: A state of hypertonicity, or increase over the normal tone of a muscle, with heightened deep tendon reflexes. [EU] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by

220 Obsessive Compulsive Disorder

refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Sperm: The fecundating fluid of the male. [NIH] Spike: The activation of synapses causes changes in the permeability of the dendritic membrane leading to changes in the membrane potential. This difference of the potential travels along the axon of the neuron and is called spike. [NIH] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Startle Reaction: A complex involuntary response to an unexpected strong stimulus usually auditory in nature. [NIH] Stereotactic: Radiotherapy that treats brain tumors by using a special frame affixed directly to the patient's cranium. By aiming the X-ray source with respect to the rigid frame, technicians can position the beam extremely precisely during each treatment. [NIH] Stereotaxis: Use of a computer and scanning devices to create three-dimensional pictures. This method can be used to direct a biopsy, external radiation, or the insertion of radiation implants. [NIH] Sterility: 1. The inability to produce offspring, i.e., the inability to conceive (female s.) or to induce conception (male s.). 2. The state of being aseptic, or free from microorganisms. [EU] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU]

Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Stool: The waste matter discharged in a bowel movement; feces. [NIH] Streptococcal: Caused by infection due to any species of streptococcus. [NIH] Streptococcal Infections: Infections with bacteria of the genus Streptococcus. [NIH] Streptococci: A genus of spherical Gram-positive bacteria occurring in chains or pairs. They are widely distributed in nature, being important pathogens but often found as normal commensals in the mouth, skin, and intestine of humans and other animals. [NIH] Streptococcus: A genus of gram-positive, coccoid bacteria whose organisms occur in pairs or chains. No endospores are produced. Many species exist as commensals or parasites on man or animals with some being highly pathogenic. A few species are saprophytes and occur in the natural environment. [NIH] Streptokinase: Streptococcal fibrinolysin . An enzyme produced by hemolytic streptococci. It hydrolyzes amide linkages and serves as an activator of plasminogen. It is used in thrombolytic therapy and is used also in mixtures with streptodornase (streptodornase and streptokinase). EC 3.4.-. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or

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tension. Stress may be either physical or psychologic, or both. [NIH] Striatum: A higher brain's domain thus called because of its stripes. [NIH] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH] Stroke Volume: The amount of blood pumped out of the heart per beat not to be confused with cardiac output (volume/time). [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] Subarachnoid: Situated or occurring between the arachnoid and the pia mater. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]

Substrate: A substance upon which an enzyme acts. [EU] Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts. [NIH] Sumatriptan: A serotonin agonist that acts selectively at 5HT1 receptors. It is used in the treatment of migraines. [NIH] Support group: A group of people with similar disease who meet to discuss how better to cope with their cancer and treatment. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Supraspinal: Above the spinal column or any spine. [NIH] Survival Rate: The proportion of survivors in a group, e.g., of patients, studied and followed over a period, or the proportion of persons in a specified group alive at the beginning of a time interval who survive to the end of the interval. It is often studied using life table methods. [NIH] Sympathetic Nervous System: The thoracolumbar division of the autonomic nervous system. Sympathetic preganglionic fibers originate in neurons of the intermediolateral column of the spinal cord and project to the paravertebral and prevertebral ganglia, which in turn project to target organs. The sympathetic nervous system mediates the body's response to stressful situations, i.e., the fight or flight reactions. It often acts reciprocally to the parasympathetic system. [NIH] Sympathomimetic: 1. Mimicking the effects of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. 2. An agent that produces effects similar to those of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. Called also adrenergic. [EU] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Symptomatology: 1. That branch of medicine with treats of symptoms; the systematic discussion of symptoms. 2. The combined symptoms of a disease. [EU]

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Synapses: Specialized junctions at which a neuron communicates with a target cell. At classical synapses, a neuron's presynaptic terminal releases a chemical transmitter stored in synaptic vesicles which diffuses across a narrow synaptic cleft and activates receptors on the postsynaptic membrane of the target cell. The target may be a dendrite, cell body, or axon of another neuron, or a specialized region of a muscle or secretory cell. Neurons may also communicate through direct electrical connections which are sometimes called electrical synapses; these are not included here but rather in gap junctions. [NIH] Synapsis: The pairing between homologous chromosomes of maternal and paternal origin during the prophase of meiosis, leading to the formation of gametes. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Synaptic Transmission: The communication from a neuron to a target (neuron, muscle, or secretory cell) across a synapse. In chemical synaptic transmission, the presynaptic neuron releases a neurotransmitter that diffuses across the synaptic cleft and binds to specific synaptic receptors. These activated receptors modulate ion channels and/or secondmessenger systems to influence the postsynaptic cell. Electrical transmission is less common in the nervous system, and, as in other tissues, is mediated by gap junctions. [NIH] Synaptic Vesicles: Membrane-bound compartments which contain transmitter molecules. Synaptic vesicles are concentrated at presynaptic terminals. They actively sequester transmitter molecules from the cytoplasm. In at least some synapses, transmitter release occurs by fusion of these vesicles with the presynaptic membrane, followed by exocytosis of their contents. [NIH] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Systemic: Affecting the entire body. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Tachycardia: Excessive rapidity in the action of the heart, usually with a heart rate above 100 beats per minute. [NIH] Tardive: Marked by lateness, late; said of a disease in which the characteristic lesion is late in appearing. [EU] Telencephalon: Paired anteriolateral evaginations of the prosencephalon plus the lamina terminalis. The cerebral hemispheres are derived from it. Many authors consider cerebrum a synonymous term to telencephalon, though a minority include diencephalon as part of the cerebrum (Anthoney, 1994). [NIH] Temperament: Predisposition to react to one's environment in a certain way; usually refers to mood changes. [NIH] Temporal: One of the two irregular bones forming part of the lateral surfaces and base of the skull, and containing the organs of hearing. [NIH] Temporal Lobe: Lower lateral part of the cerebral hemisphere. [NIH] Terbutaline: A selective beta-2 adrenergic agonist used as a bronchodilator and tocolytic. [NIH]

Thalamic: Cell that reaches the lateral nucleus of amygdala. [NIH] Thalamus: Paired bodies containing mostly gray substance and forming part of the lateral wall of the third ventricle of the brain. The thalamus represents the major portion of the

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diencephalon and is commonly divided into cellular aggregates known as nuclear groups. [NIH]

Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thinness: A state of insufficient flesh on the body usually defined as having a body weight less than skeletal and physical standards. [NIH] Third Ventricle: A narrow cleft inferior to the corpus callosum, within the diencephalon, between the paired thalami. Its floor is formed by the hypothalamus, its anterior wall by the lamina terminalis, and its roof by ependyma. It communicates with the fourth ventricle by the cerebral aqueduct, and with the lateral ventricles by the interventricular foramina. [NIH] Thorax: A part of the trunk between the neck and the abdomen; the chest. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombocytes: Blood cells that help prevent bleeding by causing blood clots to form. Also called platelets. [NIH] Thrombolytic: 1. Dissolving or splitting up a thrombus. 2. A thrombolytic agent. [EU] Thrombolytic Therapy: Use of infusions of fibrinolytic agents to destroy or dissolve thrombi in blood vessels or bypass grafts. [NIH] Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation. [NIH]

Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Tic: An involuntary compulsive, repetitive, stereotyped movement, resembling a purposeful movement because it is coordinated and involves muscles in their normal synergistic relationships; tics usually involve the face and shoulders. [EU] Tidal Volume: The volume of air inspired or expired during each normal, quiet respiratory cycle. Common abbreviations are TV or V with subscript T. [NIH] Tinnitus: Sounds that are perceived in the absence of any external noise source which may take the form of buzzing, ringing, clicking, pulsations, and other noises. Objective tinnitus refers to noises generated from within the ear or adjacent structures that can be heard by other individuals. The term subjective tinnitus is used when the sound is audible only to the affected individual. Tinnitus may occur as a manifestation of cochlear diseases; vestibulocochlear nerve diseases; intracranial hypertension; craniocerebral trauma; and other conditions. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tolerance: 1. The ability to endure unusually large doses of a drug or toxin. 2. Acquired drug tolerance; a decreasing response to repeated constant doses of a drug or the need for increasing doses to maintain a constant response. [EU] Tomography: Imaging methods that result in sharp images of objects located on a chosen plane and blurred images located above or below the plane. [NIH]

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Tonic: 1. Producing and restoring the normal tone. 2. Characterized by continuous tension. 3. A term formerly used for a class of medicinal preparations believed to have the power of restoring normal tone to tissue. [EU] Tonicity: The normal state of muscular tension. [NIH] Tooth Preparation: Procedures carried out with regard to the teeth or tooth structures preparatory to specified dental therapeutic and surgical measures. [NIH] Topical: On the surface of the body. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxins: Specific, characterizable, poisonous chemicals, often proteins, with specific biological properties, including immunogenicity, produced by microbes, higher plants, or animals. [NIH] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Translation: The process whereby the genetic information present in the linear sequence of ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH] Translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Treatment Outcome: Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, practicability, etc., of these interventions in individual cases or series. [NIH]

Tremor: Cyclical movement of a body part that can represent either a physiologic process or a manifestation of disease. Intention or action tremor, a common manifestation of cerebellar diseases, is aggravated by movement. In contrast, resting tremor is maximal when there is no attempt at voluntary movement, and occurs as a relatively frequent manifestation of Parkinson disease. [NIH] Trichotillomania: Compulsion to pull out one's hair. [NIH] Tricuspid Atresia: Absence of the orifice between the right atrium and ventricle, with the presence of an atrial defect through which all the systemic venous return reaches the left heart. As a result, there is left ventricular hypertrophy because the right ventricle is absent or not functional. [NIH] Tricyclic: Containing three fused rings or closed chains in the molecular structure. [EU]

Dictionary 225

Trigger zone: Dolorogenic zone (= producing or causing pain). [EU] Tryptophan: An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor serotonin and niacin. [NIH] Tyramine: An indirect sympathomimetic. Tyramine does not directly activate adrenergic receptors, but it can serve as a substrate for adrenergic uptake systems and monoamine oxidase so it prolongs the actions of adrenergic transmitters. It also provokes transmitter release from adrenergic terminals. Tyramine may be a neurotransmitter in some invertebrate nervous systems. [NIH] Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Ultrasonography: The visualization of deep structures of the body by recording the reflections of echoes of pulses of ultrasonic waves directed into the tissues. Use of ultrasound for imaging or diagnostic purposes employs frequencies ranging from 1.6 to 10 megahertz. [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]

Uric: A kidney stone that may result from a diet high in animal protein. When the body breaks down this protein, uric acid levels rise and can form stones. [NIH] Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urinary tract: The organs of the body that produce and discharge urine. These include the kidneys, ureters, bladder, and urethra. [NIH] Urinate: To release urine from the bladder to the outside. [NIH] Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH] Uterine Contraction: Contraction of the uterine muscle. [NIH] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vagus Nerve: The 10th cranial nerve. The vagus is a mixed nerve which contains somatic afferents (from skin in back of the ear and the external auditory meatus), visceral afferents (from the pharynx, larynx, thorax, and abdomen), parasympathetic efferents (to the thorax and abdomen), and efferents to striated muscle (of the larynx and pharynx). [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vascular Resistance: An expression of the resistance offered by the systemic arterioles, and to a lesser extent by the capillaries, to the flow of blood. [NIH] Vasoconstriction: Narrowing of the blood vessels without anatomic change, for which constriction, pathologic is used. [NIH] Vasodilator: An agent that widens blood vessels. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venous: Of or pertaining to the veins. [EU] Ventral: 1. Pertaining to the belly or to any venter. 2. Denoting a position more toward the belly surface than some other object of reference; same as anterior in human anatomy. [EU] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives

226 Obsessive Compulsive Disorder

oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH] Ventricular: Pertaining to a ventricle. [EU] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Vertebrae: A bony unit of the segmented spinal column. [NIH] Vestibulocochlear Nerve: The 8th cranial nerve. The vestibulocochlear nerve has a cochlear part (cochlear nerve) which is concerned with hearing and a vestibular part (vestibular nerve) which mediates the sense of balance and head position. The fibers of the cochlear nerve originate from neurons of the spiral ganglion and project to the cochlear nuclei (cochlear nucleus). The fibers of the vestibular nerve arise from neurons of Scarpa's ganglion and project to the vestibular nuclei. [NIH] Vestibulocochlear Nerve Diseases: Diseases of the vestibular and/or cochlear (acoustic) nerves, which join to form the vestibulocochlear nerve. Vestibular neuritis, cochlear neuritis, and acoustic neuromas are relatively common conditions that affect these nerves. Clinical manifestations vary with which nerve is primarily affected, and include hearing loss, vertigo, and tinnitus. [NIH] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Viscera: Any of the large interior organs in any one of the three great cavities of the body, especially in the abdomen. [NIH] Visceral: , from viscus a viscus) pertaining to a viscus. [EU] Visceral Afferents: The sensory fibers innervating the viscera. [NIH] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] Void: To urinate, empty the bladder. [NIH] Volition: Voluntary activity without external compulsion. [NIH] War: Hostile conflict between organized groups of people. [NIH] Weight Gain: Increase in body weight over existing weight. [NIH] White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]

Withdrawal: 1. A pathological retreat from interpersonal contact and social involvement, as may occur in schizophrenia, depression, or schizoid avoidant and schizotypal personality disorders. 2. (DSM III-R) A substance-specific organic brain syndrome that follows the cessation of use or reduction in intake of a psychoactive substance that had been regularly used to induce a state of intoxication. [EU] Xenograft: The cells of one species transplanted to another species. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to

Dictionary 227

treat cancer. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH] Zygote: The fertilized ovum. [NIH] Zymogen: Inactive form of an enzyme which can then be converted to the active form, usually by excision of a polypeptide, e. g. trypsinogen is the zymogen of trypsin. [NIH]

229

INDEX 3 3-dimensional, 114, 169 A Abdomen, 169, 177, 199, 220, 223, 225, 226 Abdominal, 169, 207, 211 Aberrant, 58, 92, 169, 181 Accommodation, 169, 187 Acetylcholine, 117, 169, 180, 205 Activities of Daily Living, 169, 187 Acute renal, 169, 194 Acyl, 121, 169 Adaptation, 7, 169, 180 Adipose Tissue, 121, 169 Adjunctive Therapy, 53, 169 Adjustment, 169 Adolescence, 6, 18, 22, 46, 169 Adrenal Cortex, 169, 184, 212 Adrenal Medulla, 170, 179, 190, 205 Adrenergic, 116, 126, 170, 171, 173, 187, 190, 221, 222, 225 Adrenergic Agonists, 126, 170 Adverse Effect, 170, 174, 216, 218 Afferent, 19, 170, 211 Affinity, 20, 52, 123, 124, 170, 174, 218, 219 Affinity Chromatography, 52, 170 Agar, 170, 210 Agonist, 20, 21, 85, 89, 90, 111, 116, 121, 170, 171, 174, 175, 187, 203, 205, 208, 221, 222 Agoraphobia, 111, 170, 196, 207, 209 Airway, 170, 177, 219 Akathisia, 170, 173 Albumin, 170, 210 Albuterol, 126, 170 Alexia, 171, 188 Algorithms, 171, 176 Alkaline, 171, 178 Alkaloid, 171, 181, 203, 205, 216 Alleles, 34, 40, 171, 195, 199 Allergen, 171, 186 Alternative medicine, 95, 98, 140, 171, 182 Amenorrhea, 171, 172 Amine, 171, 195 Amino Acid Neurotransmitters, 42, 171 Amino Acid Sequence, 171, 172, 192 Amino Acids, 171, 176, 192, 205, 208, 211, 213, 217, 224 Amnesia, 136, 171

Amnestic, 111, 171, 191, 201 Amniotic Fluid, 171, 193, 206 Amphetamine, 34, 115, 171, 176, 186 Amygdala, 23, 172, 175, 199, 222 Anaesthesia, 172, 197 Anal, 19, 29, 30, 172, 190, 199 Analgesic, 112, 172, 203 Anatomical, 12, 18, 20, 172, 174, 183, 196, 217 Anemia, 172, 192 Anesthesia, 136, 170, 172 Animal model, 23, 32, 59, 115, 172 Anomalies, 172, 203 Anorexia, 20, 24, 25, 30, 51, 58, 64, 70, 82, 87, 102, 103, 110, 111, 120, 141, 172 Anorexia Nervosa, 20, 24, 51, 64, 70, 87, 102, 103, 111, 172 Antecedent, 45, 47, 172 Antibacterial, 172, 220 Antibiotic, 48, 105, 172, 208, 220 Antibodies, 35, 48, 105, 172, 175, 194, 200, 210 Antibody, 9, 35, 48, 170, 172, 173, 182, 194, 195, 196, 197, 201, 215, 219 Anticoagulant, 172, 213 Anticonvulsant, 172, 178, 180 Antidepressant, 38, 59, 63, 112, 117, 118, 120, 122, 129, 135, 172, 177, 180, 191, 196 Antidiuretic, 172, 204 Antiemetic, 172, 173, 180 Antigen, 35, 170, 172, 173, 182, 195, 196, 197, 201 Antihypertensive, 173, 208, 216 Anti-inflammatory, 173, 197 Antimetabolite, 173, 186 Antimicrobial, 48, 173 Antipsychotic, 5, 38, 115, 120, 135, 173, 179, 187, 204, 216, 217 Antipsychotic Agents, 173, 187 Antiviral, 173, 186 Anus, 172, 173, 177, 198 Anxiety Disorders, 14, 15, 16, 17, 20, 23, 24, 25, 38, 44, 49, 69, 79, 111, 117, 128, 131, 132, 173, 207 Anxiolytic, 117, 173, 206 Aorta, 173, 188, 226 Apathy, 173, 204 Aphasia, 171, 173

230 Obsessive Compulsive Disorder

Apnea, 121, 174, 219 Apomorphine, 66, 92, 174 Aqueous, 174, 175, 189 Arachidonic Acid, 174, 212 Arginine, 174, 205 Aromatic, 174, 176, 209 Arterial, 174, 184, 195, 213, 222 Arteries, 4, 173, 174, 177, 179, 184, 202, 214 Arterioles, 174, 177, 225 Arteriolosclerosis, 174 Arteriosclerosis, 4, 174 Articular, 174, 199, 207 Articulation, 18, 174 Artifacts, 44, 174 Assay, 57, 174 Astrocytes, 174, 203 Atrial, 174, 184, 224 Atrioventricular, 174, 184 Atrium, 174, 184, 224, 226 Atypical, 55, 120, 175, 217 Auditory, 23, 135, 175, 201, 211, 220, 225 Autacoids, 175, 197 Autoantibodies, 175 Autoantigens, 7, 175 Autoimmune disease, 175, 210 Autonomic, 23, 169, 173, 175, 192, 205, 221 Autoradiography, 8, 175 Autoreceptors, 51, 53, 175 B Baclofen, 86, 175 Bacteria, 105, 169, 172, 173, 175, 202, 220, 224, 225 Bacterial Physiology, 169, 175 Bactericidal, 175, 190 Bacteriophage, 175, 210, 224 Bacterium, 175, 182, 194 Basal Ganglia, 9, 12, 19, 27, 52, 73, 173, 175, 177, 180, 196, 199, 214 Basal Ganglia Diseases, 12, 175, 180, 196 Base, 13, 44, 175, 185, 186, 192, 198, 222 Behavior Therapy, 11, 54, 55, 58, 59, 79, 83, 88, 100, 157, 175, 181 Behavioral Symptoms, 51, 176 Benign, 174, 176, 194 Bewilderment, 176, 183 Bile, 176, 192, 199, 220 Bioavailability, 20, 176 Biochemical, 171, 173, 176, 207, 218 Biogenic Amines, 61, 176 Biological Markers, 46, 176 Biological Psychiatry, 58, 61, 64, 65, 66, 73, 78, 92, 96, 115, 176

Biological Sciences, 50, 176 Biological Transport, 176, 186 Biophysics, 176 Biopsy, 5, 176, 220 Biosynthesis, 112, 174, 176 Biotechnology, 56, 57, 135, 140, 149, 176 Bipolar Disorder, 38, 48, 64, 110, 113, 115, 123, 157, 176 Bladder, 121, 176, 197, 225, 226 Blastocyst, 177, 183 Blinking, 116, 177 Blood Coagulation, 177, 178, 223 Blood Platelets, 177, 218 Blood pressure, 4, 124, 173, 177, 178, 179, 192, 195, 196, 203, 206, 214, 219 Blood vessel, 4, 177, 178, 179, 184, 188, 189, 190, 193, 194, 209, 219, 221, 223, 225 Blood-Brain Barrier, 111, 177, 201 Bowel, 172, 177, 186, 196, 220 Bowel Movement, 177, 186, 196, 220 Bradykinin, 177, 205, 210 Brain Diseases, 114, 177 Branch, 106, 165, 177, 185, 189, 201, 205, 208, 214, 219, 221, 223 Bronchial, 177, 195 Bronchodilator, 177, 222 Bulimia, 58, 85, 111, 141, 177 Bupropion, 120, 122, 177 C Calcification, 174, 177 Calcium, 126, 177, 178, 182, 218 Calcium channel blocker, 126, 178 Calcium Channel Blockers, 126, 178 Calculi, 178, 193 Carbamazepine, 82, 178 Carbohydrate, 178, 211, 217 Carbon Dioxide, 178, 185, 195, 216 Carcinogenic, 178, 212, 220 Cardiac, 45, 124, 126, 178, 184, 189, 190, 203, 220, 221 Cardiac arrest, 126, 178 Cardiac Output, 124, 178, 221 Cardiovascular, 4, 121, 126, 172, 178, 218 Cardiovascular disease, 121, 178 Case report, 63, 76, 84, 87, 96, 117, 178 Case series, 61, 80, 178 Catalogs, 157, 178 Catecholamine, 179, 187, 208 Caudal, 179, 186, 196, 211 Caudate Nucleus, 35, 175, 179, 204 Causal, 179, 190 Cell Differentiation, 179, 218

Index 231

Cell Division, 175, 179, 185, 201, 210, 212, 218 Cell membrane, 176, 178, 179, 186, 192, 209 Cell proliferation, 174, 179, 218 Central Nervous System Infections, 179, 194 Cerebellum, 177, 179 Cerebral Arteries, 179, 202 Cerebrospinal, 61, 66, 105, 179 Cerebrospinal fluid, 61, 66, 105, 179 Cerebrovascular, 175, 178, 179 Cerebrum, 179, 222 Chemoreceptor, 173, 179 Child Psychiatry, 32, 35, 36, 78, 116, 179 Child Psychology, 7, 81, 179 Chlorpromazine, 115, 179, 191 Cholesterol, 83, 176, 180, 184, 220 Cholinergic, 115, 173, 180, 205 Chorea, 7, 11, 35, 41, 45, 104, 173, 180 Choreatic Disorders, 180 Chromosomal, 17, 37, 180 Chromosome, 30, 43, 180, 199, 218 Chronic, 4, 8, 10, 11, 14, 15, 26, 30, 36, 41, 46, 48, 51, 81, 105, 111, 114, 117, 135, 180, 186, 197, 200, 213, 221 Circadian, 112, 120, 180 Circadian Rhythm, 112, 120, 180 CIS, 111, 180 Cisplatin, 180, 206 Citalopram, 48, 122, 128, 180 Clinical trial, 5, 13, 14, 21, 31, 42, 44, 46, 49, 101, 106, 117, 149, 180, 184, 203, 209, 213, 215 Clomipramine, 44, 48, 63, 66, 67, 68, 84, 85, 92, 103, 104, 180 Clonazepam, 63, 116, 180 Clone, 35, 181 Clonic, 180, 181 Cloning, 176, 181 Clot Retraction, 181, 210 Coagulation, 124, 177, 178, 181, 194, 210, 223 Coca, 181 Cocaine, 40, 119, 181 Cochlear, 181, 223, 226 Cochlear Diseases, 181, 223 Coenzymes, 181, 205 Cofactor, 181, 213, 223 Cognition, 13, 42, 181, 198, 204 Cognitive behavior therapy, 11, 181 Cognitive Therapy, 13, 14, 15, 22, 58, 181

Cohort Studies, 181, 190 Collagen, 182, 210, 212 Collapse, 182, 219 Comorbidity, 20, 43, 64, 92, 182 Competency, 15, 182 Complement, 182, 200, 210 Complementary and alternative medicine, 95, 98, 182 Complementary medicine, 95, 182 Complete remission, 183, 216 Compulsion, 43, 141, 183, 224, 226 Compulsive Behavior, 50, 134, 183 Computational Biology, 149, 183 Computed tomography, 183 Computer Simulation, 31, 183 Computerized axial tomography, 183 Computerized tomography, 84, 183 Conception, 38, 183, 191, 220 Concomitant, 3, 4, 183 Confusion, 68, 183, 187, 204 Congestion, 173, 183 Congestive heart failure, 124, 183 Connective Tissue, 182, 183, 192, 200 Consciousness, 172, 183, 185, 187 Constipation, 173, 183 Constriction, 183, 225 Constriction, Pathologic, 183, 225 Contamination, 80, 97, 113, 184, 206 Contraindications, ii, 184 Control group, 18, 21, 184, 209 Controlled study, 10, 79, 184 Convulsions, 172, 184, 189 Coordination, 44, 179, 184 Cor, 65, 66, 184 Coronary, 124, 178, 184, 202 Coronary heart disease, 178, 184 Coronary Thrombosis, 184, 202 Corpus, 64, 184, 193, 200, 204, 208, 212, 223 Cortex, 18, 22, 27, 40, 42, 50, 78, 102, 169, 177, 179, 184, 190, 191, 202, 211, 212 Cortical, 18, 19, 24, 42, 50, 101, 121, 135, 184, 190, 211, 218 Cortisol, 66, 67, 73, 92, 170, 184 Cranial, 179, 184, 185, 194, 198, 225, 226 Craniocerebral Trauma, 175, 185, 194, 223 Cross-Sectional Studies, 185, 190 Cues, 18, 185 Curative, 185, 205, 223 Cutaneous, 5, 185 Cyclic, 185, 193, 205, 209, 213, 217 Cytogenetics, 36, 185

232 Obsessive Compulsive Disorder

Cytotoxic, 185, 206, 218 Cytotoxic chemotherapy, 185, 206 D Databases, Bibliographic, 149, 185 Deamination, 185, 203 Decarboxylation, 176, 185, 195 Degenerative, 185, 203, 207 Delirium, 173, 185 Delusions, 5, 185, 207, 214 Dementia, 50, 111, 173, 185, 201 Dendrites, 53, 186, 204 Dendritic, 186, 220 Density, 34, 40, 50, 186, 206 Deoxyglucose, 39, 186 Depersonalization, 186, 207, 217 Depolarization, 186, 218 Depressive Disorder, 15, 16, 17, 38, 64, 78, 120, 123, 186, 199 Derealization, 186, 207 Dermatitis, 5, 186, 188 Desensitization, 53, 186 Detoxification, 122, 186 Deuterium, 186, 195 Dextroamphetamine, 172, 186 Diabetes Insipidus, 123, 124, 186 Diagnostic procedure, 44, 109, 140, 186 Diastolic, 186, 195 Diencephalon, 186, 196, 211, 222, 223 Diffusion, 27, 40, 176, 186, 197 Digestive system, 107, 186 Dilatation, 187, 212 Direct, iii, 50, 51, 143, 181, 187, 216, 220, 222 Disabled Children, 26, 187 Discrimination, 31, 187 Disease Susceptibility, 35, 187 Disinfectant, 187, 190 Disorientation, 183, 185, 187 Dissociation, 170, 187 Dissociative Disorders, 113, 187 Distal, 187, 189, 211, 213 Dizziness, 187, 207 Dominance, 8, 187 Dopamine Antagonists, 115, 187 Dorsal, 18, 41, 187, 211 Dorsum, 187, 188 Drive, ii, vi, 30, 91, 188, 197, 199 Drug Interactions, 144, 188 Drug Monitoring, 49, 188 Drug Tolerance, 188, 223 Ductus Arteriosus, 126, 188 Dyskinesia, 115, 116, 173, 180, 188

Dyslexia, 11, 188, 199 Dysmenorrhea, 82, 124, 125, 126, 127, 188 Dysphoria, 50, 188 Dysphoric, 42, 51, 186, 188 Dyspnea, 188, 207 Dystonia, 73, 102, 173, 188 E Eating Disorders, 8, 20, 30, 52, 58, 59, 64, 82, 92, 102, 113, 119, 121, 125, 128, 141, 156, 188 Eczema, 4, 188 Effector, 169, 182, 188, 205, 209 Effector cell, 188, 205 Ego, 188, 206, 215 Ejaculation, 111, 112, 188, 218 Elasticity, 174, 188 Elective, 82, 111, 188 Electrocoagulation, 181, 189 Electroconvulsive Therapy, 135, 189 Electrode, 114, 136, 189 Electrons, 175, 189, 198, 200, 215 Electrophysiological, 10, 23, 119, 189 Elementary Particles, 189, 200, 213 Embryo, 177, 179, 189, 197 Emetic, 174, 189 Empiric, 38, 189 Empirical, 15, 56, 189 Emulsion, 175, 189 Encapsulated, 110, 189 Encephalitis, 189, 201 Endocrine System, 189 Endocrinology, 42, 189 Endometrium, 189, 201 Endothelial cell, 177, 189, 223 Endothelium, 190, 205, 210 Endothelium-derived, 190, 205 Enuresis, 123, 124, 190 Environmental Exposure, 176, 190 Environmental Health, 148, 150, 190 Enzymatic, 52, 176, 178, 182, 190, 195 Enzyme, 176, 181, 188, 190, 193, 197, 202, 203, 209, 210, 213, 218, 220, 221, 223, 226, 227 Epidemiologic Studies, 44, 176, 190 Epidemiological, 5, 36, 73, 190 Epinephrine, 170, 176, 187, 190, 205, 225 Epithelial, 124, 176, 190 Erectile, 3, 128, 190, 208 Erection, 128, 190, 197 Esophagus, 186, 190, 208, 220 Essential Tremor, 114, 190 Estrogen, 190, 212

Index 233

Ethanol, 119, 180, 190 Eukaryotic Cells, 190, 197 Evoke, 190, 220 Excitatory, 171, 175, 190, 193 Exogenous, 187, 188, 190, 213 Exotoxin, 35, 191 Extensor, 191, 213 External radiation, 191, 220 Extracellular, 51, 53, 123, 174, 183, 191, 202, 219 Extracellular Space, 191, 202 Extrapyramidal, 170, 173, 187, 191 F Facial, 116, 191, 201 Family Planning, 149, 191 Family Relations, 10, 191 Fat, 111, 121, 169, 174, 184, 191, 199 Fatigue, 191, 194 Fatty acids, 170, 191, 212 Feeding Behavior, 20, 191 Fetal Blood, 188, 191 Fetus, 191, 211 Fibrin, 177, 181, 191, 210, 223 Fissure, 191, 211 Fluoxetine, 24, 25, 42, 44, 47, 48, 49, 52, 58, 61, 63, 66, 67, 76, 79, 85, 96, 116, 122, 127, 128, 144, 191 Fluphenazine, 116, 191 Fluvoxamine, 25, 48, 49, 57, 63, 68, 80, 97, 122, 128, 191 Folate, 191 Fold, 6, 21, 191 Folic Acid, 93, 191 Food Preferences, 18, 192 Forearm, 177, 192 Frontal Lobe, 41, 57, 96, 114, 192, 211 Functional magnetic resonance imaging, 7, 18, 23, 28, 40, 192 G GABA, 42, 86, 171, 175, 181, 192, 218 Gallbladder, 169, 187, 192 Ganglia, 9, 12, 19, 27, 52, 73, 169, 173, 175, 177, 180, 192, 196, 199, 204, 214, 221 Ganglionic Blockers, 192, 201 Gap Junctions, 192, 222 Gas, 178, 186, 192, 195, 205, 214 Gastric, 192, 195 Gastrin, 192, 195 Gastrointestinal, 111, 119, 177, 180, 190, 192, 201, 218, 221 Gastrointestinal tract, 111, 180, 190, 192, 201, 218

Gene, 27, 33, 37, 38, 39, 51, 60, 66, 76, 105, 123, 135, 171, 176, 187, 192, 195, 218 Gene Expression, 37, 105, 192 Genetic Code, 192, 206 Genetic testing, 43, 192 Genetics, 6, 29, 30, 33, 36, 39, 47, 60, 64, 73, 77, 86, 103, 185, 187, 192 Genomics, 37, 192 Genotype, 28, 39, 192, 208 Germ Cells, 193, 201, 219 Gestation, 126, 193, 208 Gestational, 126, 127, 193 Gestational Age, 126, 127, 193 Gland, 112, 169, 170, 193, 200, 207, 217, 220, 223 Globus Pallidus, 9, 175, 193, 214 Glomerular, 193 Glomeruli, 193 Glomerulonephritis, 34, 193, 196 Glomerulus, 35, 193, 204 Glucose, 80, 97, 186, 193, 215, 217 Glutamate, 42, 78, 123, 171, 193 Glutamic Acid, 171, 191, 193, 212 Gonad, 193 Gonadal, 81, 193, 220 Gout, 121, 193 Governing Board, 193, 211 Graft, 193, 195, 196 Granulocytes, 193, 218, 226 Grasses, 191, 193 Growth, 14, 86, 169, 172, 173, 179, 193, 200, 206, 210, 217, 223, 225 Guanylate Cyclase, 193, 205 H Hallucination, 194 Hallucinogen, 32, 194 Haloperidol, 115, 116, 194 Haplotypes, 36, 194 Haptens, 170, 194 Headache, 111, 194, 211 Headache Disorders, 194 Heart attack, 178, 194 Heart failure, 124, 183, 194 Hemicrania, 111, 194 Hemodynamics, 3, 194 Hemolytic, 45, 105, 194, 220 Hemorrhage, 185, 189, 194, 221 Hemostasis, 194, 218 Hereditary, 180, 193, 194, 203, 204 Heredity, 192, 194 Heritability, 30, 194

234 Obsessive Compulsive Disorder

Heterogeneity, 17, 28, 30, 31, 33, 34, 44, 170, 194 Heterozygotes, 187, 195 Hiccup, 180, 187, 195 Histamine, 117, 173, 176, 195 Histidine, 195 Homogeneous, 17, 27, 28, 174, 195 Homologous, 53, 171, 195, 218, 222 Homozygotes, 187, 195 Hormonal, 3, 195, 208 Hormone, 86, 124, 175, 176, 180, 184, 190, 192, 195, 204, 207, 212, 217, 218, 223 Host, 138, 175, 195, 196 Hybrid, 52, 181, 195 Hydrogen, 121, 171, 175, 178, 186, 195, 203, 208, 213 Hyperlipidemia, 121, 195 Hyperphagia, 43, 121, 195 Hyperplasia, 11, 195 Hypersensitivity, 102, 116, 171, 186, 195 Hypertension, 4, 111, 121, 124, 174, 178, 184, 194, 195, 198, 201, 214, 223 Hypertrophy, 184, 195, 224 Hyperuricemia, 193, 195 Hyperventilation, 78, 195 Hypochondriasis, 69, 113, 195 Hypokinesia, 196, 207 Hypotension, 126, 173, 184, 192, 196 Hypotensive, 124, 196 Hypothalamus, 53, 177, 186, 196, 199, 223 I Id, 93, 98, 157, 164, 166, 188, 196 Idiopathic, 73, 196 Imipramine, 180, 196 Immune Complex Diseases, 196, 210 Immune function, 77, 97, 196 Immune response, 41, 173, 175, 194, 196, 200, 221, 226 Immune system, 105, 188, 196, 200, 203, 225, 226 Immunoglobulin, 47, 172, 196 Immunologic, 48, 193, 196 Immunology, 41, 170, 196 Immunotherapy, 186, 196 Impairment, 7, 11, 15, 16, 17, 26, 28, 47, 55, 84, 111, 113, 176, 185, 188, 196, 201, 214 Implantation, 183, 196 Impotence, 128, 190, 196 Impotent, 128, 197 Impulse Control Disorders, 113, 197 In situ, 8, 197 In Situ Hybridization, 8, 197

In vitro, 10, 32, 197 In vivo, 8, 19, 32, 42, 53, 63, 106, 124, 197, 202 Incision, 197, 198 Incontinence, 124, 197 Indicative, 132, 197, 208, 225 Indomethacin, 126, 197 Induction, 115, 173, 192, 197, 212 Infarction, 173, 184, 197, 202 Infection, 11, 41, 45, 47, 104, 105, 185, 189, 196, 197, 200, 208, 220, 221, 226 Infertility, 121, 197 Infiltration, 193, 197 Inflammation, 170, 173, 186, 189, 197, 204, 208 Inotropic, 187, 197 Inpatients, 65, 197 Insight, 9, 18, 34, 39, 47, 197 Insomnia, 120, 198, 211 Intermittent, 198, 200 Internal Medicine, 189, 198 Interstitial, 191, 198, 204 Intestines, 169, 187, 192, 198 Intoxication, 185, 198, 226 Intracellular, 178, 197, 198, 205, 213, 215, 217, 218 Intracranial Hypertension, 194, 198, 223 Intravenous, 47, 48, 72, 103, 104, 198 Intrinsic, 9, 170, 198 Invasive, 42, 102, 198, 200 Involuntary, 116, 175, 177, 180, 190, 198, 203, 216, 220, 223 Ion Channels, 174, 198, 205, 222 Ions, 175, 187, 195, 198, 202 J Jealousy, 198, 207 Joint, 174, 198, 207 K Kb, 148, 198 Kinetic, 42, 198 L Lactation, 38, 198, 207, 212 Lag, 27, 49, 52, 198 Language Development, 132, 198 Large Intestine, 187, 198, 215, 219 Larynx, 198, 225 Latent, 31, 199 Learning Disorders, 131, 199 Lesion, 199, 222 Leukocytes, 193, 197, 199 Libido, 120, 199 Library Services, 164, 199

Index 235

Ligaments, 184, 199 Ligands, 119, 125, 199 Limbic, 8, 19, 97, 172, 199, 211 Limbic System, 172, 199, 211 Linkage, 17, 28, 30, 33, 37, 39, 66, 199 Linkage Disequilibrium, 28, 34, 66, 199 Lipid, 4, 174, 199 Lithium, 157, 173, 199 Liver, 169, 170, 174, 176, 180, 187, 189, 191, 192, 199, 203 Lobe, 41, 57, 96, 114, 172, 192, 199, 211, 222 Localization, 38, 199 Localized, 4, 22, 102, 189, 197, 199, 203, 210 Longitudinal study, 43, 48, 199 Long-Term Care, 37, 200 Loop, 19, 200 Lutein Cells, 200, 212 Lymph, 189, 190, 196, 200 Lymph node, 196, 200 Lymphatic, 190, 197, 200 Lymphocyte, 62, 173, 200, 201 Lymphocyte Subsets, 62, 200 Lymphoid, 172, 200 M Magnetic Resonance Imaging, 7, 18, 23, 27, 28, 41, 192, 200 Magnetic Resonance Spectroscopy, 42, 200 Maintenance therapy, 104, 200 Major Histocompatibility Complex, 194, 200 Malaise, 188, 200 Malignant, 72, 174, 200 Mania, 8, 59, 114, 157, 200, 201 Manic, 157, 173, 176, 199, 201, 214 Manic-depressive psychosis, 201, 214 Manifest, 45, 201 Meatus, 201, 225 Mecamylamine, 115, 201 Medial, 8, 9, 18, 174, 193, 201, 206 Mediate, 8, 12, 43, 66, 86, 119, 187, 188, 201 Mediator, 46, 201, 218 Medicament, 127, 201 MEDLINE, 149, 201 Megaloblastic, 192, 201 Meiosis, 201, 222 Melanin, 201, 209, 225 Membrane, 52, 174, 179, 182, 186, 190, 198, 201, 202, 203, 209, 218, 220, 222, 224 Memory, 18, 70, 75, 84, 111, 171, 172, 185, 201

Memory Disorders, 111, 201 Meninges, 179, 185, 201 Menstrual Cycle, 42, 201, 211, 212 Menstruation, 171, 188, 201, 211 Mental Disorders, 7, 22, 46, 49, 50, 107, 179, 196, 201, 213, 214 Mentors, 37, 41, 42, 44, 50, 202 Mesolimbic, 173, 202 Meta-Analysis, 60, 202 Metabolic disorder, 186, 193, 202 Metabolite, 180, 202, 212 Methanol, 110, 202 Methyltransferase, 112, 202 MI, 104, 117, 119, 168, 202 Microbiology, 169, 175, 202 Microdialysis, 53, 202 Microorganism, 181, 202, 207, 226 Microscopy, 9, 202 Middle Cerebral Artery, 74, 202 Mode of Transmission, 33, 202 Modeling, 14, 29, 42, 202 Modification, 202, 214 Modulator, 123, 202 Molecular, 6, 17, 36, 39, 50, 52, 66, 76, 111, 149, 151, 176, 183, 185, 202, 210, 212, 215, 224 Molecular Structure, 202, 224 Molecule, 20, 35, 110, 170, 173, 175, 182, 187, 188, 190, 202, 215, 218, 221 Monitor, 19, 203, 206 Monoamine, 64, 71, 84, 117, 120, 122, 171, 186, 203, 225 Monoamine Oxidase, 117, 171, 186, 203, 225 Monotherapy, 21, 55, 203 Mood Disorders, 8, 25, 42, 52, 73, 111, 131, 203 Morphine, 174, 203 Morphology, 64, 203 Motility, 111, 112, 197, 203, 218 Movement Disorders, 62, 114, 115, 173, 203 Mucosa, 203, 212 Multicenter Studies, 44, 203 Multicenter study, 203 Mutilation, 82, 203 Myocardium, 202, 203 N Naive, 64, 203 Naloxone, 71, 116, 203 Nausea, 172, 173, 203, 206, 207, 211 NCI, 1, 106, 147, 180, 203

236 Obsessive Compulsive Disorder

Necrosis, 197, 202, 204 Need, 3, 11, 17, 22, 34, 40, 47, 50, 53, 110, 113, 126, 127, 131, 135, 141, 159, 204, 223 Neonatal, 38, 204 Neostriatum, 179, 204, 214 Nephritis, 35, 204 Nephrogenic, 124, 204 Nephron, 193, 204 Nerve, 53, 114, 118, 170, 172, 186, 201, 203, 204, 211, 217, 220, 223, 224, 225, 226 Networks, 43, 204 Neural, 4, 24, 26, 27, 28, 41, 44, 71, 95, 114, 170, 192, 203, 204, 208 Neural Pathways, 4, 204 Neuroanatomy, 39, 44, 50, 199, 204 Neurodegenerative Diseases, 175, 204 Neuroleptic, 4, 55, 111, 115, 170, 173, 204, 206 Neurologic, 7, 21, 115, 204 Neurology, 12, 21, 45, 65, 75, 131, 204 Neuromuscular, 169, 204 Neuromuscular Junction, 169, 204 Neuronal, 12, 51, 68, 180, 204 Neurons, 9, 12, 19, 121, 122, 171, 181, 186, 190, 192, 204, 205, 215, 221, 222, 226 Neuropeptide, 105, 115, 205 Neuropharmacology, 42, 50, 89, 115, 205 Neuropsychology, 40, 44, 75, 84, 89, 205 Neurosis, 196, 205, 206, 209 Neurosurgery, 70, 97, 114, 205 Neurotic, 5, 114, 205 Neurotransmitters, 42, 122, 171, 205, 212 Niacin, 111, 205, 225 Nicotine, 115, 205, 206 Nitric Oxide, 114, 115, 205 Nitrogen, 171, 205, 225 Nocturia, 123, 124, 205 Nonverbal Communication, 205, 214 Norepinephrine, 122, 170, 187, 205, 216 Nuclear, 42, 175, 189, 190, 191, 199, 204, 205, 206, 223 Nuclear Family, 191, 206 Nuclei, 53, 114, 172, 189, 199, 200, 206, 213, 215, 226 Nucleic acid, 123, 192, 197, 205, 206 O Observational study, 27, 44, 206 Obsession, 6, 141, 183, 206 Obsessional, 6, 43, 133, 206 Odds Ratio, 206, 216 Oligohydramnios, 126, 206 Ondansetron, 45, 206

Opacity, 186, 206 Optic Chiasm, 196, 206 Orbit, 206 Orbital, 18, 41, 206 Orderly, 18, 206 Orgasm, 188, 206 Orthostatic, 173, 207 Osteoarthritis, 121, 207 Outpatient, 10, 14, 24, 25, 48, 207 Ovum, 193, 207, 212, 227 Oxytocin, 78, 87, 92, 123, 124, 125, 126, 127, 207 P Palliative, 207, 223 Pancreas, 169, 187, 207 Panic, 24, 29, 38, 39, 50, 57, 78, 92, 111, 113, 117, 118, 119, 121, 125, 128, 191, 196, 207 Panic Disorder, 29, 38, 39, 57, 78, 92, 111, 113, 117, 118, 121, 125, 128, 191, 196, 207 Paranoia, 40, 207 Paresthesias, 207 Parkinsonism, 111, 173, 174, 207 Paroxetine, 39, 48, 49, 127, 128, 207 Paroxysmal, 111, 194, 207 Partial remission, 207, 216 Partial response, 44, 49, 55, 207 Parturition, 207, 212 Pathogen, 47, 207 Pathogenesis, 7, 37, 46, 86, 116, 207 Pathologic, 176, 177, 183, 184, 195, 208, 213, 225 Pathologies, 114, 208 Pathophysiology, 9, 12, 17, 22, 34, 41, 42, 87, 208 Patient Education, 4, 162, 164, 168, 208 Pedigree, 17, 208 Penicillin, 104, 208 Penis, 4, 188, 208 Peptide, 20, 208, 211, 213 Perception, 136, 186, 194, 208, 217 Pergolide, 21, 208 Perinatal, 126, 127, 208 Periodicity, 81, 208 Pernicious, 26, 201, 208 Personality Disorders, 14, 15, 16, 208, 226 PH, 84, 208 Pharmacologic, 4, 5, 25, 65, 72, 79, 87, 157, 172, 175, 208, 224 Pharmacotherapy, 11, 14, 15, 39, 51, 55, 67, 79, 96, 115, 208 Pharyngitis, 48, 208 Pharynx, 208, 225

Index 237

Phenotype, 17, 28, 33, 37, 39, 43, 123, 176, 208 Phenyl, 123, 209 Phenylalanine, 209, 225 Phobia, 5, 8, 13, 24, 89, 95, 111, 117, 119, 125, 132, 209 Phobic Disorders, 78, 209 Phosphodiesterase, 127, 128, 209 Phospholipases, 209, 218 Phospholipids, 191, 209 Phosphorus, 178, 209 Photocoagulation, 181, 209 Phototherapy, 209, 217 Physical Examination, 193, 209 Physician Assistants, 4, 209 Physiologic, 170, 176, 196, 201, 209, 212, 215, 218, 224 Physiology, 114, 169, 175, 176, 189, 209 Pilot study, 22, 30, 51, 54, 69, 209 Placebos, 105, 209 Plants, 171, 176, 178, 181, 193, 203, 205, 210, 217, 224 Plaque, 4, 210 Plasma, 46, 67, 105, 170, 172, 179, 194, 210, 218 Plasma cells, 172, 210 Plasma Exchange, 46, 210 Plasma protein, 170, 210 Plasmapheresis, 47, 210 Plasmin, 35, 210 Plasminogen, 210, 220 Plasminogen Activators, 210 Platelet Activation, 210, 219 Platelet Aggregation, 205, 210 Platelets, 85, 177, 205, 210, 218, 223 Platinum, 180, 200, 210 Poisoning, 174, 185, 198, 203, 206, 211 Polymorphism, 51, 211 Polypeptide, 171, 182, 210, 211, 212, 227 Polysaccharide, 173, 211 Posterior, 172, 179, 188, 207, 211 Postsynaptic, 211, 218, 222 Post-synaptic, 34, 53, 211 Post-traumatic, 13, 24, 49, 111, 119, 194, 203, 211 Post-traumatic stress disorder, 13, 111, 211 Potentiates, 67, 211 Potentiation, 23, 211, 218 Practicability, 211, 224 Practice Guidelines, 56, 150, 211

Precursor, 174, 187, 188, 190, 205, 209, 210, 211, 212, 225 Prefrontal Cortex, 18, 27, 40, 78, 211 Pregnancy Tests, 193, 211 Premenstrual, 42, 52, 211 Premenstrual Syndrome, 52, 211 Prenatal, 115, 189, 211 Presynaptic, 122, 175, 211, 222 Presynaptic Terminals, 175, 211, 222 Prevalence, 6, 14, 20, 29, 31, 37, 49, 58, 80, 119, 128, 206, 212 Probe, 9, 202, 212 Prodrug, 111, 212 Progesterone, 212, 220 Progression, 52, 172, 212 Progressive, 174, 179, 185, 188, 193, 204, 207, 210, 212 Projection, 19, 205, 211, 212 Prolactin, 67, 212 Proline, 123, 182, 212 Promoter, 51, 212 Prophase, 212, 222 Prospective Studies, 53, 212 Prospective study, 73, 199, 212 Prostaglandin, 126, 212 Prostaglandins A, 197, 212, 213 Protective Agents, 178, 213 Protein Binding, 38, 213 Protein C, 34, 121, 170, 171, 175, 213 Protein S, 135, 176, 192, 213, 217 Proteins, 35, 52, 171, 173, 179, 182, 192, 203, 205, 208, 210, 213, 215, 218, 224 Proteolytic, 182, 210, 213 Protocol, 11, 19, 22, 24, 209, 213 Protons, 195, 200, 213, 215 Proximal, 187, 211, 213 Pruritic, 188, 213 Psoriasis, 4, 213 Psychic, 199, 205, 214, 218 Psychogenic, 4, 128, 214 Psychology, 7, 13, 14, 16, 20, 21, 23, 31, 75, 81, 96, 100, 120, 133, 179, 183, 187, 205, 214 Psychomotor, 178, 185, 204, 214 Psychopathology, 10, 21, 23, 29, 31, 46, 54, 62, 71, 214 Psychophysiology, 21, 205, 214 Psychosis, 38, 64, 71, 120, 125, 128, 173, 193, 201, 214 Psychotherapy, 11, 14, 22, 58, 75, 96, 135, 181, 214, 215 Psychotomimetic, 171, 186, 214

238 Obsessive Compulsive Disorder

Public Health, 33, 45, 55, 150, 214 Public Policy, 149, 214 Publishing, 56, 214 Pulmonary, 177, 184, 188, 195, 214, 226 Pulmonary Artery, 177, 188, 214, 226 Pulmonary hypertension, 184, 214 Pulmonary Ventilation, 195, 214 Pulse, 48, 102, 104, 203, 214 Putamen, 175, 204, 214 Pyrogenic, 35, 214 Q Quality of Life, 26, 102, 157, 214 R Race, 170, 215 Radiation, 169, 175, 189, 190, 191, 215, 220, 226 Radiation therapy, 169, 191, 215 Radioactive, 175, 195, 196, 206, 215 Radiography, 193, 215 Radiolabeled, 32, 215 Rage, 115, 215 Randomized, 10, 11, 13, 15, 21, 22, 32, 44, 49, 58, 68, 103, 188, 215 Randomized clinical trial, 13, 44, 215 Rape, 211, 215 Raphe Nuclei, 53, 215 Reabsorption, 124, 215 Reality Testing, 214, 215 Reassurance, 196, 215 Receptors, Serotonin, 215, 218 Recombinant, 35, 215 Rectum, 173, 177, 187, 192, 197, 198, 215 Recur, 208, 216, 217 Recurrence, 176, 180, 201, 208, 216, 217 Red blood cells, 194, 216, 217 Refer, 1, 182, 187, 199, 203, 204, 214, 216 Reflex, 23, 216 Refraction, 216, 220 Refractory, 39, 46, 70, 81, 120, 189, 216 Regimen, 188, 208, 216 Relapse, 24, 25, 26, 38, 54, 85, 216 Relative risk, 39, 216 Relaxation Techniques, 5, 216 Reliability, 26, 216 Remission, 11, 26, 176, 183, 200, 201, 207, 216 Research Design, 13, 21, 31, 33, 39, 41, 216 Research Support, 39, 216 Reserpine, 112, 216 Respiration, 174, 178, 179, 203, 216 Response rate, 15, 216 Reticulata, 18, 216

Retrospective, 44, 216 Ribosome, 217, 224 Rigidity, 207, 210, 217 Risk factor, 13, 23, 190, 212, 216, 217 Risperidone, 39, 55, 82, 116, 217 S Saline, 210, 217 Salivary, 186, 217 Salivary glands, 186, 217 Saponins, 217, 220 Schizoid, 217, 226 Schizotypal Personality Disorder, 186, 217, 226 Sclerosis, 174, 217 Screening, 33, 35, 44, 180, 217 Seasonal Affective Disorder, 111, 217 Second Messenger Systems, 205, 217 Secretion, 67, 111, 112, 180, 195, 198, 217, 218 Secretory, 119, 217, 222 Sedative, 112, 196, 217 Segregation, 33, 64, 218 Seizures, 136, 178, 180, 185, 207, 218 Semen, 188, 218 Sequencing, 14, 39, 218 Serotonin, 11, 32, 33, 34, 42, 43, 47, 48, 49, 50, 51, 52, 55, 57, 61, 66, 70, 71, 76, 77, 82, 83, 85, 87, 106, 110, 111, 112, 117, 118, 119, 120, 121, 122, 125, 127, 128, 173, 176, 180, 191, 203, 206, 207, 208, 215, 216, 217, 218, 221, 225 Serotonin Agonists, 218 Serotonin Antagonists, 85, 218 Sertraline, 49, 55, 75, 83, 111, 122, 127, 128, 218 Serum, 35, 38, 47, 83, 93, 170, 182, 196, 218 Sex Characteristics, 169, 218 Shock, 135, 218, 224 Side effect, 4, 20, 32, 49, 52, 114, 116, 117, 126, 129, 143, 170, 173, 180, 195, 218, 224 Signal Transduction, 52, 218 Signs and Symptoms, 216, 219 Skeletal, 219, 223 Skeleton, 198, 212, 219 Skull, 102, 185, 206, 219, 222 Sleep apnea, 121, 219 Small intestine, 195, 198, 219 Smooth muscle, 175, 177, 178, 195, 203, 219, 221 Social Environment, 214, 219 Social Problems, 18, 219 Sodium, 193, 215, 219

Index 239

Solvent, 190, 202, 219 Soma, 53, 219 Somatic, 47, 89, 169, 199, 201, 207, 211, 219, 225 Spasticity, 175, 219 Specialist, 158, 219 Species, 8, 121, 190, 195, 201, 215, 219, 220, 221, 226 Specificity, 9, 14, 23, 35, 52, 170, 219, 221 Spectrum, 4, 20, 22, 28, 36, 37, 45, 66, 80, 99, 135, 219 Sperm, 180, 220 Spike, 9, 220 Spinal cord, 121, 174, 175, 179, 180, 201, 204, 205, 216, 220, 221 Startle Reaction, 23, 220 Stereotactic, 70, 97, 114, 220 Stereotaxis, 114, 220 Sterility, 197, 220 Steroid, 38, 184, 217, 220 Stimulant, 26, 171, 186, 195, 220 Stimulus, 24, 40, 84, 188, 189, 194, 198, 207, 209, 216, 220, 223 Stomach, 169, 186, 190, 192, 195, 198, 203, 208, 219, 220 Stool, 197, 198, 220 Streptococcal, 11, 34, 41, 45, 47, 77, 97, 104, 105, 220 Streptococcal Infections, 35, 77, 97, 105, 220 Streptococci, 220 Streptococcus, 47, 104, 105, 220 Streptokinase, 35, 220 Stress, 4, 5, 11, 13, 24, 49, 50, 111, 119, 132, 179, 184, 203, 211, 220 Striatum, 9, 18, 44, 193, 204, 221 Stroke, 107, 121, 148, 178, 221 Stroke Volume, 178, 221 Subacute, 197, 221 Subarachnoid, 194, 221 Subclinical, 20, 84, 197, 218, 221 Subspecies, 219, 221 Substance P, 202, 217, 221 Substrate, 52, 85, 221, 225 Substrate Specificity, 52, 221 Sumatriptan, 85, 89, 221 Support group, 158, 221 Suppression, 4, 21, 100, 124, 125, 126, 127, 221 Supraspinal, 175, 221 Survival Rate, 124, 125, 126, 127, 221 Sympathetic Nervous System, 205, 221

Sympathomimetic, 171, 186, 187, 190, 205, 221, 225 Symptomatic, 12, 47, 221 Symptomatology, 20, 137, 221 Synapses, 123, 205, 220, 222 Synapsis, 222 Synaptic, 9, 34, 51, 53, 117, 123, 205, 211, 218, 222 Synaptic Transmission, 123, 205, 222 Synaptic Vesicles, 222 Synergistic, 50, 120, 212, 222, 223 Systemic, 124, 144, 173, 177, 185, 190, 194, 196, 197, 198, 215, 222, 224, 225 Systolic, 195, 222 T Tachycardia, 126, 222 Tardive, 111, 115, 116, 173, 180, 222 Telencephalon, 175, 222 Temperament, 24, 222 Temporal, 9, 12, 50, 172, 194, 201, 222 Temporal Lobe, 172, 222 Terbutaline, 126, 222 Thalamic, 8, 9, 18, 22, 222 Thalamus, 18, 23, 113, 114, 177, 186, 199, 211, 222 Therapeutics, 20, 26, 34, 52, 144, 203, 223 Thinness, 30, 223 Third Ventricle, 196, 222, 223 Thorax, 169, 223, 225 Threshold, 136, 195, 223 Thrombin, 191, 210, 213, 223 Thrombocytes, 210, 223 Thrombolytic, 210, 220, 223 Thrombolytic Therapy, 220, 223 Thrombomodulin, 213, 223 Thrombosis, 184, 202, 213, 221, 223 Thyroid, 223, 225 Tidal Volume, 195, 223 Tinnitus, 135, 223, 226 Tolerance, 117, 180, 188, 223 Tomography, 34, 39, 51, 80, 84, 97, 183, 200, 223 Tonic, 24, 180, 224 Tonicity, 188, 224 Tooth Preparation, 169, 224 Topical, 190, 224 Toxic, iv, 190, 191, 193, 202, 205, 224 Toxicity, 188, 224 Toxicology, 150, 224 Toxins, 173, 189, 197, 224 Transduction, 52, 218, 224 Transfection, 176, 224

240 Obsessive Compulsive Disorder

Translation, 36, 41, 46, 224 Translational, 37, 46, 224 Transmitter, 169, 174, 175, 187, 198, 201, 205, 222, 224, 225 Trauma, 36, 135, 175, 185, 194, 204, 223, 224 Treatment Outcome, 10, 14, 44, 46, 49, 55, 224 Tremor, 114, 190, 207, 224 Trichotillomania, 5, 21, 81, 102, 103, 157, 224 Tricuspid Atresia, 184, 224 Tricyclic, 5, 63, 67, 117, 123, 124, 125, 126, 127, 180, 196, 224 Trigger zone, 173, 225 Tryptophan, 72, 182, 218, 225 Tyramine, 176, 203, 225 Tyrosine, 52, 187, 225 U Ultrasonography, 193, 225 Unconscious, 8, 196, 225 Urethra, 208, 225 Uric, 193, 195, 225 Urinary, 123, 124, 178, 190, 197, 206, 225 Urinary tract, 206, 225 Urinate, 225, 226 Urine, 71, 105, 124, 172, 176, 186, 190, 197, 204, 225 Uterine Contraction, 207, 225 V Vaccine, 213, 225 Vagus Nerve, 118, 225 Vascular, 111, 124, 178, 190, 194, 197, 205, 210, 225 Vascular Resistance, 124, 225 Vasoconstriction, 124, 190, 225

Vasodilator, 177, 187, 195, 225 Vein, 198, 206, 225 Venous, 213, 224, 225 Ventral, 18, 41, 196, 225 Ventricle, 172, 174, 179, 184, 196, 214, 222, 223, 224, 225, 226 Ventricular, 184, 224, 226 Venules, 177, 226 Vertebrae, 220, 226 Vestibulocochlear Nerve, 223, 226 Vestibulocochlear Nerve Diseases, 223, 226 Veterinary Medicine, 149, 226 Virus, 175, 179, 210, 224, 226 Viscera, 219, 226 Visceral, 199, 225, 226 Visceral Afferents, 225, 226 Vitro, 10, 32, 197, 226 Vivo, 8, 19, 32, 42, 53, 63, 106, 124, 197, 202, 226 Void, 43, 226 Volition, 198, 206, 226 W War, 211, 226 Weight Gain, 116, 122, 217, 226 White blood cell, 172, 199, 200, 210, 226 Withdrawal, 4, 185, 226 X Xenograft, 172, 226 X-ray, 183, 206, 215, 220, 226 Y Yeasts, 208, 227 Z Zygote, 183, 227 Zymogen, 213, 227

Index 241

242 Obsessive Compulsive Disorder

Index 243

244 Obsessive Compulsive Disorder