Textbook Anxiety Disorders Second Edition (1)

Textbook of Anxiety Disorders

SECOND EDITION

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Washington, DCLondon, England

Textbook ofAnxiety Disorders

Edited byDan J. Stein, M.D., Ph.D.

Eric Hollander, M.D.Barbara O. Rothbaum, Ph.D., ABPP

Note: The authors have worked to ensure that all information in this book is accurate at the time of publication andconsistent with general psychiatric and medical standards, and that information concerning drug dosages, schedules, androutes of administration is accurate at the time of publication and consistent with standards set by the U.S. Food and DrugAdministration and the general medical community. As medical research and practice continue to advance, however,therapeutic standards may change. Moreover, specific situations may require a specific therapeutic response not includedin this book. For these reasons and because human and mechanical errors sometimes occur, we recommend that readersfollow the advice of physicians directly involved in their care or the care of a member of their family.

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DSM-IV-TR criteria included in this book are reprinted, with permission, from the Diagnostic and Statistical Manualof Mental Disorders, 4th Edition, Text Revision. Copyright 2000, American Psychiatric Association.

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Library of Congress Cataloging-in-Publication DataTextbook of anxiety disorders / edited by Dan J. Stein, Eric Hollander, Barbara O. Rothbaum. 2nd ed. p. ; cm. Includes bibliographical references and index. ISBN 978-1-58562-254-2 (alk. paper) 1. Anxiety disordersTextbooks. I. Stein, Dan J. II. Hollander, Eric, 1957- III. Rothbaum, Barbara Olasov. [DNLM: 1. Anxiety Disorders. WM 172 T356 2010] RC531.A525 2010 616.8522dc22 2009015495

British Library Cataloguing in Publication DataA CIP record is available from the British Library.

ContentsContributors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xi

Disclosure of Interests. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xvii

Foreword. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .xxiJerilyn Ross, M.A., L.I.C.S.W.

Preface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .xxiiiDan J. Stein, M.D., Ph.D.Eric Hollander, M.D.Barbara O. Rothbaum, Ph.D., ABPP

PART IApproaching the Anxiety Disorders

1 History of Anxiety Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3Michael H. Stone, M.D.

2 Classification of Anxiety Disorders. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17Timothy A. Brown, Psy.D.Ovsanna Leyfer, Ph.D.

3 Preclinical Models of Anxiety . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35Nicola D. Hanson, B.S.Charles B. Nemeroff, M.D., Ph.D.

4 Neural Circuits in Fear and Anxiety . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55J. Douglas Bremner, M.D.Dennis S. Charney, M.D.

5 Anxious Traits and Temperaments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73Steven Taylor, Ph.D., ABPPJonathan S. Abramowitz, Ph.D., ABPPDean McKay, Ph.D.Gordon J.G. Asmundson, Ph.D.

6 The Neuropsychology of Anxiety Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87Kevin J. Craig, M.B.B.Ch., M.Phil., MRCPsych Samuel R. Chamberlain, Ph.D., M.B.B.Ch.

7 Cognitive-Behavioral Concepts of Anxiety . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 103Robert A. DiTomasso, Ph.D., ABPPArthur Freeman, Ed.D., ABPPRaymond Carvajal, M.A.Bruce Zahn, Ed.D., ABPP

8 Psychodynamic Concepts of Anxiety . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 117Fredric N. Busch, M.D.Barbara L. Milrod, M.D.M. Katherine Shear, M.D.

9 Evolutionary Concepts of Anxiety . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 129Myron A. Hofer, M.D.

10 Combined Treatment of Anxiety Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 147Maryrose Gerardi, Ph.D.Kerry Ressler, M.D., Ph.D.Barbara Olasov Rothbaum, Ph.D.

PART IIGeneralized Anxiety Disorder

11 Phenomenology of Generalized Anxiety Disorder . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 159Laszlo A. Papp, M.D.

12 Pathogenesis of Generalized Anxiety Disorder. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 173Jeffrey D. Lightfoot, Ph.D.Steven Seay Jr., M.S.Andrew W. Goddard, M.D.

13 Pharmacotherapy for Generalized Anxiety Disorder . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 193Michael Van Ameringen, M.D., FRCPCCatherine Mancini, M.D., FRCPCBeth Patterson, B.Sc.N., B.Ed.William Simpson, B.Sc.Christine Truong, B.Sc.

14 Psychotherapy for Generalized Anxiety Disorder . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 219Jonathan D. Huppert, Ph.D.William C. Sanderson, Ph.D.

PART IIIMixed Anxiety-Depression

15 Mixed Anxiety-Depressive Disorder: An Undiagnosed and Undertreated Severity Spectrum? . . . . 241Jan Fawcett, M.D.Rebecca P. Cameron, Ph.D.Alan F. Schatzberg, M.D.

PART IVObsessive-Compulsive Disorder/Related Disorders

16 Phenomenology of Obsessive-Compulsive Disorder . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 261Jane L. Eisen, M.D.Agustin G. Yip, M.D., Ph.D.Maria C. Mancebo, Ph.D.Anthony Pinto, Ph.D.Steven A. Rasmussen, M.D.

17 Pathophysiology of Obsessive-Compulsive Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 287Darin D. Dougherty, M.D.Scott L. Rauch, M.D.Benjamin D. Greenberg, M.D., Ph.D.

18 Pharmacotherapy for Obsessive-Compulsive Disorder. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 311Naomi A. Fineberg, M.B.B.S., M.A., MRCPsychKevin J. Craig, M.B.B.Ch., M.Phil., MRCPsych

19 Psychological Treatment for Obsessive-Compulsive Disorder . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 339Jonathan S. Abramowitz, Ph.D., ABPP

20 The Obsessive-Compulsive Spectrum of Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 355Sarah Ketay, Ph.D.Dan J. Stein, M.D., Ph.D.Eric Hollander, M.D.

PART VPanic Disorder/Agoraphobia

21 Phenomenology of Panic Disorder . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 367Mark H. Pollack, M.D.Jordan W. Smoller, M.D., Sc.D.Michael W. Otto, Ph.D.Elizabeth Hoge, M.D.Naomi Simon, M.D., M.Sc.

22 Pathogenesis of Panic Disorder. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 381Ranjeeb Shrestha, M.D.Navin Natarajan, M.D.Jeremy D. Coplan, M.D.

23 Pharmacotherapy for Panic Disorder . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 399Borwin Bandelow, M.D., Ph.D.David S. Baldwin, M.D.

24 Psychotherapy for Panic Disorder . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 417Stefan G. Hofmann, Ph.D.Winfried Rief, Ph.D.David A. Spiegel, M.D.

PART VISocial Anxiety Disorder (Social Phobia)

25 Phenomenology of Social Anxiety Disorder . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 437Holly J. Ramsawh, Ph.D.Denise A. Chavira, Ph.D.Murray B. Stein, M.D., M.P.H.

26 Pathogenesis of Social Anxiety Disorder . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 453Mary Morreale, M.D.Manuel E. Tancer, M.D.Thomas W. Uhde, M.D.

27 Pharmacotherapy for Social Anxiety Disorder . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 471Carlos Blanco, M.D., Ph.D.Franklin R. Schneier, M.D.Oriana Vesga-Lpez, M.D.Michael R. Liebowitz, M.D.

28 Psychotherapy for Social Anxiety Disorder. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 501Kristin E. Pontoski, M.A.Richard G. Heimberg, Ph.D.Cynthia L. Turk, Ph.D.Meredith E. Coles, Ph.D.

PART VIISpecific Phobia

29 Specific Phobia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 525Amanda L. Gamble , Ph.D.Allison G. Harvey, Ph.D.Ronald M. Rapee, Ph.D.

PART VIIIPosttraumatic Stress Disorder/Acute Stress Disorder

30 Phenomenology of Posttraumatic Stress Disorder . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 547Alexander C. McFarlane, M.D.

31 Pathogenesis of Posttraumatic Stress Disorder and Acute Stress Disorder. . . . . . . . . . . . . . . . . . . . 567Rachel Yehuda, Ph.D.Casey Sarapas, B.S.

32 Pharmacotherapy for Posttraumatic Stress Disorder. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 583Wei Zhang, M.D., Ph.D.Jonathan R.T. Davidson, M.D.

33 Psychotherapy for Posttraumatic Stress Disorder . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 603Monnica T. Williams, Ph.D.Shawn P. Cahill, Ph.D.Edna B. Foa, Ph.D.

PART IXAnxiety Disorders in Special Populations

34 Anxiety Disorders in Children and Adolescents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 629Phoebe S. Moore, Ph.D.John S. March, M.D., M.P.H.Anne Marie Albano, Ph.D., ABPPMargo Thienemann, M.D.

35 Anxiety Disorders in the Elderly . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 651Eric J. Lenze, M.D.

36 Anxiety in the Context of Substance Abuse . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 665Sudie E. Back, Ph.D.Angela E. Waldrop, Ph.D.Kathleen T. Brady, M.D., Ph.D.

37 Anxiety and Anxiety Disorders in Medical Settings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 681Thomas N. Wise, M.D.Michael J. Marcangelo, M.D.Danielle L. Anderson, M.D.

38 Anxiety and Insomnia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 699Thomas W. Uhde, M.D.Bernadette M. Cortese, Ph.D.

PART XSocial Aspects of Anxiety Disorders

39 Cultural and Social Aspects of Anxiety Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 717Dan J. Stein, M.D., Ph.D.David Williams, Ph.D.

40 The Economic and Social Burden of Anxiety Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 731David F. Tolin, Ph.D.Christina M. Gilliam, Ph.D.Danielle Dufresne, M.A.

41 Consumer Considerations. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 747Jerilyn Ross, M.A., L.I.C.S.W.

Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 757

xi

ContributorsJonathan S. Abramowitz, Ph.D., ABPPProfessor, Department of Psychology, and Director, Anx-iety and Stress Disorders Clinic, University of NorthCarolina at Chapel Hill

Anne Marie Albano, Ph.D., ABPPDirector, Columbia University Clinic for Anxiety and Re-lated Disorders, Columbia University Medical Center,New York, New York

Danielle L. Anderson, M.D.Assistant Professor, Department of Psychiatry and Behav-ioral Neuroscience, University of Chicago Hospitals, Chi-cago, Illinois

Gordon J.G. Asmundson, Ph.D.Professor and Research Director, Faculty of Kinesiologyand Health Studies, University of Regina, Saskatchewan,Canada

Sudie E. Back, Ph.D.Associate Professor, Clinical Neuroscience Division, De-partment of Psychiatry and Behavioral Sciences, TheMedical University of South Carolina, Charleston, SouthCarolina

David S. Baldwin, M.D.Clinical Neuroscience Division, School of Medicine, Uni-versity of Southampton, Southampton, United Kingdom

Borwin Bandelow, M.D., Ph.D.Department of Psychiatry and Psychotherapy, Universityof Gttingen, Gttingen, Germany

Carlos Blanco, M.D., Ph.D.Associate Professor of Clinical Psychiatry, New York StatePsychiatric Institute/Department of Psychiatry, College ofPhysicians and Surgeons of Columbia University, NewYork, New York

Kathleen T. Brady, M.D., Ph.D.Professor and Director, Clinical Neuroscience Division,The Medical University of South Carolina, Charleston,South Carolina

J. Douglas Bremner, M.D.Professor of Psychiatry and Radiology, Emory UniversitySchool of Medicine, Atlanta, Georgia; Director of MentalHealth Research, Atlanta Veterans Affairs Medical Cen-ter, Decatur, Georgia

Timothy A. Brown, Psy.D.Professor, Center for Anxiety and Related Disorders, Bos-ton University, Boston, Massachusetts

Fredric N. Busch, M.D.Clinical Associate Professor of Psychiatry, Weill CornellMedical College; Faculty, Columbia University Center forPsychoanalytic Training and Research, New York, New York

Shawn P. Cahill, Ph.D.Assistant Professor, Department of Psychology, College ofLetters and Science, University of Wisconsin, Milwaukee

Rebecca P. Cameron, Ph.D.Associate Professor, Department of Psychology, CaliforniaState University, Sacramento

Raymond Carvajal, M.A.Doctoral Student, Department of Psychology, Philadel-phia College of Osteopathic Medicine, Philadelphia,Pennsylvania

Samuel R. Chamberlain, Ph.D., M.B.B.Ch.Senior Visiting Clinical Research Fellow, Brain MappingUnit, Department of Psychiatry, University of CambridgeSchool of Clinical Medicine, Addenbrookes Hospital,Cambridge; Clinical Research Associate, Behavioural andClinical Neuroscience Institute, University of Cambridge,Cambridge, United Kingdom

xii TEXTBOOK OF ANXIETY DISORDERS

Dennis S. Charney, M.D.Dean, Mount Sinai School of Medicine, New York, NewYork

Denise A. Chavira, Ph.D.Assistant Professor, Department of Psychiatry, Universityof California, San Diego

Meredith E. Coles, Ph.D.Assistant Professor, Department of Psychology, Bingham-ton University (SUNY), Binghamton, New York

Jeremy D. Coplan, M.D.Professor of Psychiatry and Director, Division of Neuro-psychopharmacology, Department of Psychiatry, StateUniversity of New YorkDownstate Medical Center,Brooklyn, New York

Bernadette M. Cortese, Ph.D.Postdoctoral Scholar, Department of Psychiatry and Be-havioral Sciences, The Medical University of South Caro-lina, Charleston, South Carolina

Kevin J. Craig, M.B.B.Ch., M.Phil., MRCPsychMedical Director, P1vital Limited; University of OxfordDepartment of Psychiatry, Warneford Hospital, Oxford,United Kingdom

Jonathan R. T. Davidson, M.D.Professor Emeritus, Department of Psychiatry and Behav-ioral Sciences, Duke University Medical Center, Durham,North Carolina

Robert A. DiTomasso, Ph.D., ABPPProfessor and Chairman, Department of Psychology,Philadelphia College of Osteopathic Medicine, Philadel-phia, Pennsylvania

Darin D. Dougherty, M.D.Associate Professor of Psychiatry, Harvard MedicalSchool; Director of Medical Education, OCD Institute,Department of Psychiatry, Massachusetts General Hospi-tal, Boston, Massachusetts

Danielle Dufresne, M.A.Psychology Extern, University of Hartford and The Insti-tute of Living, Hartford, Connecticut

Jane L. Eisen, M.D.Associate Professor, Psychiatry and Human Behavior, andAssociate Dean, Biomedical Faculty, Warren Alpert Med-ical School of Brown University, Providence, Rhode Island

Jan Fawcett, M.D.Professor of Psychiatry, University of New Mexico Schoolof Medicine, Albuquerque, New Mexico

Naomi A. Fineberg, M.B.B.S., M.A., MRCPsychConsultant Psychiatrist and Visiting Professor of the Uni-versity of Hertfordshire, National OCD Treatment Ser-vice, Queen Elizabeth II Hospital, Welwyn, Garden City;Senior Clinical Research Fellow, Department of Psychia-try, University of Cambridge School of Clinical Medicine,Addenbrookes Hospital, Cambridge, United Kingdom

Edna B. Foa, Ph.D.Professor and Director of the Center for the Treatmentand Study of Anxiety, Department of Psychiatry, School ofMedicine, University of Pennsylvania, Philadelphia,Pennsylvania

Arthur Freeman, Ed.D., ABPPVisiting Professor, Governors State University, Chicago,Illinois; Clinical Professor, Department of Psychology,Philadelphia College of Osteopathic Medicine, Philadel-phia, Pennsylvania

Amanda L. Gamble, Ph.D.Postdoctoral Research Fellow, Centre for EmotionalHealth, Department of Psychology, Macquarie University,Sydney, Australia

Maryrose Gerardi, Ph.D.Assistant Professor, Department of Psychiatry and Behav-ioral Sciences, Emory University School of Medicine, At-lanta, Georgia

Christina M. Gilliam, Ph.D.Staff Psychologist, The Institute of Living, Hartford,Connecticut

Andrew W. Goddard, M.D.Professor of Psychiatry, Department of Psychiatry, IndianaUniversity School of Medicine, Indianapolis, Indiana

Benjamin D. Greenberg, M.D., Ph.D.Associate Professor of Psychiatry and Human Behavior,Butler Hospital, Warren Alpert Medical School ofBrown University, Providence, Rhode Island

Nicola D. Hanson, B.S.Doctoral candidate, Department of Psychiatry and Behav-ioral Sciences, Emory University School of Medicine, At-lanta, Georgia

Contributors xiii

Allison G. Harvey, Ph.D.Associate Professor, Psychology Department, Sleep andPsychological Disorders Laboratory, University of Califor-nia, Berkeley

Richard G. Heimberg, Ph.D.Professor and Distinguished Faculty Fellow in Psychology,Director of the Adult Anxiety Clinic of Temple, Depart-ment of Psychology, Temple University, Philadelphia,Pennsylvania

Myron A. Hofer, M.D.Sackler Professor and Director, Sackler Institute for De-velopmental Psychobiology, Department of Psychiatry,Columbia University College of Physicians and Surgeons,New York, New York

Stefan G. Hofmann, Ph.D.Professor of Clinical Psychology, Boston University, Bos-ton, Massachusetts

Elizabeth Hoge, M.D.Clinical Assistant in Psychiatry, Massachusetts GeneralHospital; Instructor of Psychiatry, Harvard MedicalSchool, Boston, Massachusetts

Eric Hollander, M.D.Research Attending Psychiatrist, Montefiore MedicalCenter, University Hospital of Albert Einstein College ofMedicine, New York, New York; formerly Esther and Jo-seph Klingenstein Professor and Chairman of Psychiatryand Director of the Compulsive, Impulsive and AnxietyDisorders Program, Mount Sinai School of Medicine,New York, New York

Jonathan D. Huppert, Ph.D.Associate Professor of Psychology, The Hebrew Univer-sity of Jerusalem, Mt. Scopus, Jerusalem, Israel

Sarah Ketay, Ph.D.Postdoctoral Fellow, Compulsive and Impulsive DisorderProgram, Department of Psychiatry, Mount Sinai Schoolof Medicine, New York, New York

Eric J. Lenze, M.D.Associate Professor of Psychiatry, Washington UniversitySchool of Medicine, Department of Psychiatry, St. Louis,Missouri

Ovsanna Leyfer, Ph.D.Postdoctoral Fellow, Center for Anxiety and Related Dis-orders, Boston University, Boston, Massachusetts

Michael R. Liebowitz, M.D.Professor of Clinical Psychiatry, New York State Psychiat-ric Institute/Department of Psychiatry, College of Physi-cians and Surgeons of Columbia University, New York,New York

Jeffrey D. Lightfoot, Ph.D.Clinical Assistant Professor of Psychology in Clinical Psy-chiatry, Department of Psychiatry, Indiana UniversitySchool of Medicine, Indianapolis, Indiana

Maria C. Mancebo, Ph.D.Assistant Professor, Psychiatry and Human Behavior (Re-search), Brown University, Providence, Rhode Island

Catherine Mancini, M.D., FRCPCAssociate Professor, Department of Psychiatry and Behav-ioural Neurosciences, McMaster University; Co-director,Anxiety Disorders Clinic, McMaster University MedicalCentreHamilton Health Sciences, Hamilton, Ontario,Canada

Michael J. Marcangelo, M.D.Assistant Professor, Department of Psychiatry and Behav-ioral Neuroscience, University of Chicago Hospitals, Chi-cago, Illinois

John S. March, M.D., M.P.H.Professor of Psychiatry and Behavioral Sciences and Di-rector, Division of Neurosciences Medicine, Duke ClinicalResearch Institute, Duke University Medical Center,Durham, North Carolina

Alexander C. McFarlane, M.D.Professor, Centre for Military and Veterans Health Node,University of Adelaide, South Australia

Dean McKay, Ph.D.Associate Professor, Department of Psychology, FordhamUniversity, Bronx, New York

Barbara L. Milrod, M.D.Professor of Psychiatry, Weill Cornell Medical College,and Faculty, New York Psychoanalytic Institute, NewYork, New York

Phoebe S. Moore, Ph.D.Assistant Consulting Professor, Duke University MedicalCenter, Durham, North Carolina

Mary Morreale, M.D.Assistant Professor, Department of Psychiatry, WayneState University, Detroit, Michigan

xiv TEXTBOOK OF ANXIETY DISORDERS

Navin Natarajan, M.D.Resident, Department of Psychiatry, State University of NewYorkDownstate Medical Center, Brooklyn, New York

Charles B. Nemeroff, M.D., Ph.D.Reunette W. Harris Professor, Department of Psychiatryand Behavioral Sciences, Emory University School ofMedicine, Atlanta, Georgia

Michael W. Otto, Ph.D.Director, Center for Anxiety and Related Disorders; Pro-fessor of Psychology, Boston University, Boston, Massa-chusetts

Laszlo A. Papp, M.D.Associate Professor of Clinical Psychiatry, Department ofPsychiatry, Columbia University College of Physiciansand Surgeons, New York, New York

Beth Patterson, B.Sc.N., B.Ed.Research Manager, Department of Psychiatry and Behav-ioural Neurosciences, McMaster University and AnxietyDisorders Clinic, McMaster University Medical CentreHamilton Health Sciences, Hamilton, Ontario, Canada

Anthony Pinto, Ph.D.Adjunct Assistant Professor, Psychiatry and Human Be-havior (Research), Brown University, Providence, RhodeIsland

Mark H. Pollack, M.D.Director, Center for Anxiety and Traumatic Stress Disor-ders, Massachusetts General Hospital; Professor of Psy-chiatry, Harvard Medical School, Boston, Massachusetts

Kristin E. Pontoski, M.A.Doctoral Student in Clinical Psychology, Adult AnxietyClinic of Temple, Department of Psychology, TempleUniversity, Philadelphia, Pennsylvania

Holly J. Ramsawh, Ph.D.Postdoctoral Fellow, Department of Psychiatry, Universityof California, San Diego

Ronald M. Rapee, Ph.D.Professor of Psychology and Director, Centre for Emo-tional Health, Department of Psychology, MacquarieUniversity, Sydney, Australia

Steven A. Rasmussen, M.D.Associate Professor, Psychiatry and Human Behavior,Warren Alpert Medical School of Brown University, Prov-idence, Rhode Island

Scott L. Rauch, M.D.President and Psychiatrist in Chief, McLean Hospital,Belmont, Massachusetts, Chair, Partners Psychiatryand Mental Health, and Professor of Psychiatry, Har-vard Medical School, Boston, Massachusetts

Kerry Ressler, M.D., Ph.D.Associate Professor, Department of Psychiatry and Behav-ioral Sciences, Yerkes National Primate Center, EmoryUniversity School of Medicine, Atlanta, Georgia

Winfried Rief, Ph.D.Professor of Clinical Psychology, University of Mar-burg, Marburg, Germany

Jerilyn Ross, M.A., L.I.C.S.W.President and Chief Executive Officer, Anxiety Disor-ders Association of America; Director, The Ross Cen-ter for Anxiety and Related Disorders, Washington,D.C.

Barbara Olasov Rothbaum, Ph.D., ABPPProfessor, Department of Psychiatry and BehavioralSciences, and Director, Trauma Anxiety Recovery Pro-gram, Emory University School of Medicine, Atlanta,Georgia

William C. Sanderson, Ph.D.Professor of Psychology, Hofstra University, Hemp-stead, New York

Casey Sarapas, B.S.Clinical Research Coordinator, Traumatic Stress Stud-ies Division, Mount Sinai School of Medicine, James J.Peters Veterans Affairs Medical Center, Bronx, NewYork

Alan F. Schatzberg, M.D.Professor, Department of Psychiatry and BehavioralSciences, Stanford University School of Medicine,Stanford, California

Franklin R. Schneier, M.D.Associate Professor of Clinical Psychiatry, New YorkState Psychiatric Institute/Department of Psychiatry,College of Physicians and Surgeons of Columbia Uni-versity, New York, New York

Steven Seay Jr., M.S.Student, Department of Psychology and Brain Sci-ences, Indiana University School of Medicine, Bloom-ington, Indiana

Contributors xv

M. Katherine Shear, M.D.Marion Kenworthy Professor of Psychiatry in SocialWork, Columbia University School of Social Work, NewYork, New York

Ranjeeb Shrestha, M.D.Resident, Department of Psychiatry, State University of NewYorkDownstate Medical Center, Brooklyn, New York

Naomi Simon, M.D., M.Sc.Associate Director, Center for Anxiety and TraumaticStress Disorders, Massachusetts General Hospital; Asso-ciate Professor of Psychiatry, Harvard Medical School,Boston, Massachusetts

William Simpson, B.Sc.Research Associate, Anxiety Disorders Clinic, McMasterUniversity Medical CentreHamilton Health Sciences,Hamilton, Ontario, Canada

Jordan W. Smoller, M.D., Sc.D.Director, Center for Human Genetic Research, Massa-chusetts General Hospital; Associate Professor of Psychi-atry, Harvard Medical School, Boston, Massachusetts

David A. Spiegel, M.D.Professor Emeritus, Boston University, Boston, Massa-chusetts

Dan J. Stein, M.D., Ph.D.Professor, Department of Psychiatry and Mental Health,University of Cape Town, South Africa

Murray B. Stein, M.D., M.P.H.Professor, Department of Psychiatry, Department of Fam-ily and Preventive Medicine; Director, Anxiety and Trau-matic Stress Disorders Program, University of California,San Diego

Michael H. Stone, M.D.Professor of Clinical Psychiatry, Department of Psychia-try, College of Physicians and Surgeons, Columbia Uni-versity, New York, New York

Manuel E. Tancer, M.D.Professor, Department of Psychiatry, Wayne State Univer-sity, Detroit, Michigan

Steven Taylor, Ph.D., ABPPProfessor, Department of Psychiatry, University of BritishColumbia, Vancouver, British Columbia, Canada

Margo Thienemann, M.D.Adjunct Clinical Associate Professor of Psychiatry andBehavioral Sciences, Stanford University Medical Center,Stanford, California

David F. Tolin, Ph.D.Adjunct Associate Professor of Psychiatry, The Institute ofLiving and Yale University School of Medicine, Hartford,Connecticut

Christine Truong, B.Sc.Research Associate, Anxiety Disorders Clinic, McMasterUniversity Medical CentreHamilton Health Sciences,Hamilton, Ontario, Canada

Cynthia L. Turk, Ph.D.Assistant Professor, Department of Psychology, WashburnUniversity, Topeka, Kansas

Thomas W. Uhde, M.D.Professor and Chair, Department of Psychiatry and Be-havioral Sciences, The Medical University of South Caro-lina, Charleston, South Carolina

Michael Van Ameringen, M.D., FRCPCAssociate Professor, Department of Psychiatry and Behav-ioural Neurosciences, McMaster University, and Co-Director, Anxiety Disorders Clinic, McMaster UniversityMedical CentreHamilton Health Sciences, Hamilton,Ontario, Canada

Oriana Vesga-Lpez, M.D.Research Scientist, New York State Psychiatric Institute/Department of Psychiatry, College of Physicians and Sur-geons of Columbia University, New York, New York

Angela E. Waldrop, Ph.D.Department of Psychiatry, University of California, SanFrancisco; Staff Psychologist, PTSD Clinical Team, SanFrancisco Veterans Affairs Medical Center, San Francisco,California

David Williams, Ph.D.Florence and Laura Norman Professor of Public Health,Professor of African and African American Studies and ofSociology, and Staff Director, RWJF Commission toBuild a Healthier America, Harvard School of PublicHealth, Department of Society, Human Development andHealth, Harvard University, Boston, Massachusetts

xvi TEXTBOOK OF ANXIETY DISORDERS

Monnica T. Williams, Ph.D.Assistant Professor of Psychology in Psychiatry, Depart-ment of Psychiatry, School of Medicine, University ofPennsylvania, Philadelphia, Pennsylvania

Thomas N. Wise, M.D.Professor of Psychiatry and Behavioral Sciences, JohnsHopkins University School of Medicine, Baltimore,Maryland; Chairman, Department of Psychiatry, InovaFairfax Hospital, Fairfax, Virginia

Rachel Yehuda, Ph.D.Professor of Psychiatry and Director, Traumatic StressStudies Division, Mount Sinai School of Medicine, JamesJ. Peters Veterans Affairs Medical Center, Bronx, New York

Agustin G. Yip, M.D., Ph.D.Staff Psychiatrist, Butler Hospital, Providence, Rhode Is-land

Bruce Zahn, Ed.D., ABPPProfessor, Department of Psychology, Philadelphia Col-lege of Osteopathic Medicine, Philadelphia, Pennsylvania

Wei Zhang, M.D., Ph.D.Director, Anxiety and Traumatic Stress Program, Depart-ment of Psychiatry and Behavioral Sciences, Duke Univer-sity Medical Center, Durham, North Carolina

xvii

Disclosure of Interests

The following contributors to this book have indicated a financial in-terest in or other affiliation with a commercial supporter, a manufac-turer of a commercial product, a provider of a commercial service, anongovernmental organization, and/or a government agency, aslisted below:

Anne Marie Albano, Ph.D.Grant support: National Insti-tute of Mental Health (NIMH); Royalties: Guilford Press andOxford University Press.

David S. Baldwin, M.D.Research grants Asahi, Astra-Zeneca, Cephalon, Eli Lilly, GlaxoSmithKline, Lundbeck, Or-ganon, Pharmacia, Pierre Fabre, Pfizer, Roche, Servier, Sumit-omo, and Wyeth; Consultant: Asahi, AstraZeneca, Cephalon, EliLilly, GlaxoSmithKline, Lundbeck, Organon, Pharmacia, PierreFabre, Pfizer, Roche, Servier, Sumitomo, and Wyeth.

Borwin Bandelow, M.D., Ph.D.Consultant: AstraZeneca,Cephalon, Eli Lilly, Lundbeck, Pfizer, Roche, Sanofi-Aventis,and Wyeth; Speaker's bureau/advisory board: AstraZeneca, Bris-tol-Myers Squibb, Dainippon Sumitomo, Janssen-Cilag, EliLilly, Lundbeck, Pfizer, Solvay, Wyeth, and Xian-Janssen.

Carlos Blanco, M.D., Ph.D.Research support: GlaxoSmith-Kline, Pfizer, and Somaxon.

J. Douglas Bremner, M.D.Grant support: National Insti-tutes of Health (NIH): R01 MH56120, T32 MH067547, K24MH076955; R01 AG026255, R01 HL068630, R01 HL703824,R01 MH068791, P50 MH58922 (as co-investigator), VeteransAffairs: Merit Review, VET-Heal Award, National Alliance forResearch on Schizophrenia and Depression (NARSAD) Inde-pendent Investigator Award, American Foundation for SuicidePrevention (AFSP), Georgia Research Alliance, GlaxoSmith-Kline Investigator Initiated Medical Research; Consultant:GlaxoSmithKline and Novartis; discussion of off-label medica-tion use: phenytoin.

Dennis S. Charney, M.D.Consultant: AstraZeneca, Bris-tol-Myers Squibb, Cyberonics, Neurogen, Neuroscience Educa-tion Institute, Novartis, Orexigen, and Unilever UK Central Re-sources Limited; Patent: Ketamine.

Jeremy D. Coplan, M.D.Grant funding: GlaxoSmithKlineand Pfizer; Honoraria: Bristol-Myers Squibb, Forest, and Pfizer.

Kevin J. Craig, M.B.B.Ch., M.Phil.Research support:GlaxoSmithKline; Consultant: GlaxoSmithKline.

Jonathan R.T. Davidson, M.D.Research and other support:AstraZeneca, Bristol-Myers Squibb, Cephalon, CME Institute,Forest, GlaxoSmithKline, Janssen, International Psychopharma-cology Algorithm Project, Eli Lilly, Pfizer, UCB; Speaker'sbureau: Duke University Medical Center, GlaxoSmithKline,Forest, Henry Jackson Foundation, Massachusetts PsychiatricSociety, North Carolina Psychiatric Association, Pfizer, Psychi-atric Society of Virginia, Solvay, Texas Society of PsychiatricPhysicians, University of Chicago, University of Hawaii, Univer-sity of North Carolina, and University of Utah; Advisor: Actelion,AstraZeneca, Brain Cells, Epix, Forest, GlaxoSmithKline, Jans-sen, Jazz Pharmaceuticals, Eli Lilly, MediciNova, Organon,Pfizer, Roche, Sanofi-Aventis, TransOral, and Wyeth; Royalties:American Psychiatric Association, Current Medical Science,Guilford Publications, MultiHealth Systems Inc., and Taylorand Francis; Stock: Procter and Gamble.

Darin D. Dougherty, M.D.Research funding: Cephalon,Cyberonics, Eli Lilly, Forest, McNeil, Medtronic, and NorthstarNeuroscience; Consultant/advisor: Jazz, Medtronic, and TranceptPharmaceuticals; Honoraria: Cyberonics, McNeil, Medtronic,and Northstar Neuroscience.

Naomi. A. Fineberg, M.B.B.S., M.A.Grant support: As-traZeneca, Bristol-Myers Squibb, Cephalon, Janssen, and Lun-dbeck; Consultant: GlaxoSmithKline and Lundbeck; Speaker'sbureau: AstraZeneca and Wyeth.

Andrew W. Goddard, M.D.Grant support: AstraZeneca,Janssen-McNeil, Orexigen, and Pfizer; Consultant: Orexigen;Speaker's bureau: Astra, Janssen-McNeil, Orexigen, and Pfizer;Honorarium: Orexigen.

Benjamin D. Greenberg, M.D., Ph.D.Research funding:Medtronic; Consultant: Jazz and Medtronic.

Allison G. Harvey, Ph.D.Consultant: Actelion; Speaker'sbureau: Sanofi-Aventis and Sleep Medicine Education Institute.

Stefan G. Hoffman, Ph.D.Research support: National Insti-tute of Mental Health; Consultant: Organon.

Elizabeth Hoge, M.D.Research grants: AstraZeneca, Bris-tol-Myers Squibb, Cephalon, Forest Laboratories, GlaxoSmith-Kline, Janssen, Eli Lilly, NIH, Pfizer, UCB Pharma, and Sepra-cor.

Eric Hollander, M.D.Research grants: Forest, GlaxoSmith-Kline, and Solvay; Consultant: Jazz Pharmaceuticals.

xviii TEXTBOOK OF ANXIETY DISORDERS

Eric J. Lenze, M.D.Research funding: Forest and Pfizer.Michael R. Liebowitz, M.D.Clinical trial contracts: Abbott,

AstraZeneca, Avera, Cephalon, Forest, GlaxoSmithKline, Jazz,Johnson & Johnson, Horizon, Eli Lilly, MAP, Novartis, PGXHealth, Pherin, Sepracor, Pfizer, Takeda, Tikvah, and Wyeth;Consultant: AstraZeneca, Jazz, Lilly, Pherin, Tikvah, and Wyeth;Speaker's bureau: AstraZeneca, Bristol-Myers Squibb, Jazz, andWyeth, Equity: ChiMatrix, electronic data capture, and Liebow-itz Social Anxiety Scale; Licensing software or LSAS: Avera, Glaxo-SmithKline, Indevus, Lilly, Pfizer, Servier, and Tikvah.

Catherine Mancini, M.D., FRCPCGrant/research support:AstraZeneca, Canadian Foundation for Innovation (CFI),Cephalon, GlaxoSmithKline, Eli Lilly, Janssen-Ortho, NIH,Novartis, Pfizer, Sanofi-Aventis, Servier, and Wyeth-Ayerst;Consultant: Shire; Speaker's bureau: GlaxoSmithKline.

John S. March, M.D. M.P.H.Research support: Eli Lillyand Pfizer; federal: TADS, CAMS, POTS I, II, and Jr., RUPP-PI, CAPTN, and K24; foundation: NARSAD; Consultant: Glax-oSmithKline, Lilly, Pfizer, and Wyeth; Scientific advisor: Lilly,Pfizer, and Seaside; DSMB: AstraZeneca and Johnson &Johnson; Equity: MedAvante and Multidimensional AnxietyScale for Children (MultiHealth Systems),.

Barbara L. Milrod, M.D.Lecture/speaker's bureau: NewYork Psychoanalytic Institute and Swedish Psychotherapy Asso-ciation.

Charles B. Nemeroff, M.D., Ph.D.Grant support: AFSP,NARSAD, and NIH; Scientific advisory board: AstraZeneca, For-est Laboratories, Johnson & Johnson, NARSAD, Pharma Neu-roboost, and Quintiles; Employed by: Serves on the Board of Di-rectors of AFSP, APIRE, NovaDel Pharmaceuticals, and theGeorge West Mental Health Foundation. Equity: CeNeRx andReevax. Stock: Corcept and NovaDel.

Michael W. Otto, Ph.D.Consultant/advisory board: Astra-Zeneca, Jazz Pharmaceuticals, and Organon.

Mark H. Pollack, M.D.Research grants: Bristol-MyersSquibb, Cephalon, Forest Laboratories, GlaxoSmithKline, Jans-sen, Eli Lilly, NARSAD, NIDA, NIMH, Pfizer, Sepracor, UCBPharma, and Wyeth; Consultant/advisory board: AstraZeneca,Brain Cells, Bristol-Myers Squibb, Cephalon, Forest Laborato-ries, GlaxoSmithKline, Janssen, Jazz, Eli Lilly, Medavante, Neu-rocrine, Neurogen, Novartis, Otsuka Pharmaceuticals, Pfizer,Predix, Roche Laboratories, Sanofi, Sepracor, Solvay, TikvahTherapeutics, Transcept, UCB Pharma, and Wyeth; Speaker'sbureau: Bristol-Myers Squibb, Forest Laboratories, GlaxoSmith-Kline, Janssen, Lilly, Pfizer, Solvay, and Wyeth; Equity: Meda-vante and Mensante.

Scott L. Rauch, M.D.Funded research (through Massa-chusetts General Hospital): Cyberonics and Medtronics, Inc.; Con-sultant: Novartis; Honoraria: Cyberonics, Medtronics, Neurogen,Novartis, Primedia, and Sepracor.

Kerry Ressler, M.D., Ph.D.Grant/funding support: Bur-roughs Wellcome Foundation, Lundbeck, NARSAD, NationalInstitute on Drug Abuse (NIDA), NIMH, and Pfizer; Consult-ant: Tikvah Therapeutics.

Barbara O. Rothbaum, Ph.D.Research funding: Janssen,Pfizer, and Wyeth; Consultant: Virtually Better; Scientific advi-sory board: Tikvah Therapeutics; Equity: Virtually Better.

Alan F. Schatzberg, M.D.Consultant: Abbott, Aventis,Bristol-Myers Squibb, Corcept, Eli Lilly, Forest Laboratories,GlaxoSmithKline, Innapharma, Janssen, Merck, Novartis, Or-ganon, Pharmacia, Solvay, Somerset, Wyeth; Grants: Bristol-Myers Squibb, Eli Lilly, Wyeth; Equity: Corcept, Cypress Bio-sciences, Elan, Merck, Pfizer

M. Katherine Shear, M.D.Research funding: Forest Labo-ratories; Consultant/Advisory board: Forest Laboratories andPfizer.

Naomi Simon, M.D., M.Sc.Grant/research support: Astra-Zeneca, Bristol-Myers Squibb, Cephalon, Eli Lilly, Forest Lab-oratories, GlaxoSmithKline, Janssen, NARSAD, NIMH, Pfizer,Sepracor, and UCB Pharma; Consultant/advisory board: Para-mount Biosciences and Solvay; Speaker's bureau: Forest Labora-tories, Janssen, Lilly, Pfizer, Sepracor, and UCB Pharma.

Jordan W. Smoller, M.D., Sc.D.Consultant: Eli Lilly; Ad-visory board: Roche Diagnostics.

Dan J. Stein, M.D., Ph.D.Research grant: AstraZeneca, EliLilly, GlaxoSmithKline, Johnson & Johnson, Lundbeck, Orion,Pfizer, Pharmacia, Roche, Servier, Solvay, Sumitomo, Tikvah,and Wyeth; Consultant: AstraZeneca, Eli Lilly, GlaxoSmith-Kline, Johnson & Johnson, Lundbeck, Orion, Pfizer, Pharmacia,Roche, Servier, Solvay, Sumitomo, Tikvah, and Wyeth.

Murray B. Stein, M.D., M.P.H., FRCPCResearch support:Eli Lilly, Forest Laboratories and GlaxoSmithKline; Consultant:AstraZeneca, Avera, Bristol-Myers Squibb, Eli Lilly & Com-pany, Forest Laboratories, GlaxoSmithKline, Hoffman-LaRoche, Integral Health Decisions, Jazz, Johnson & Johnson,Pfizer, and Virtual Reality Medical Center; Stock: Co-owner ofNeuroMarkers.

Thomas W. Uhde, M.D.Speaker's bureau: Jazz Pharmaceu-ticals.

Michael Van Ameringen, M.D.Grant/research support: As-traZeneca, Cephalon, Eli Lilly, GlaxoSmithKline, Janssen-Ortho, National Institutes of Health (NIH), Novartis, Pfizer,Servier, and Wyeth-Ayerst; Consultant: Biovail, Cephalon,GlaxoSmithKline, Janssen-Ortho, Novartis, Pfizer, Servier,Shire, and Wyeth-Ayerst; Speaker's bureau: GlaxoSmithKline,Janssen-Ortho, Pfizer, and Wyeth-Ayerst.

Angela E. Waldrop, Ph.D.Research support: NIH.Thomas N. Wise, M.D.Speaker's bureau: Eli Lilly and

Pfizer.

Disclosure of Interests xix

The following authors have no competing interests to report:

Jonathan S. Abramowitz, Ph.D.Danielle L. Anderson, M.D.Gordon J.G. Asmundson, Ph.D.Sudie Back, Ph.D.Kathleen T. Brady, M.D., Ph.D.Timothy A. Brown, Psy.D.Fredric N. Busch, M.D.Shawn P. Cahill, Ph.D.Rebecca P. Cameron, Ph.D.Raymond Carvajal, M.A.Samuel R. Chamberlain, Ph.D., M.B.B.Ch.Denise A. Chavira, Ph.D.Meredith E. Coles, Ph.D.Bernadette M. Cortese, Ph.D.Robert A. DiTomasso, Ph.D.Danielle Dufresne, M.A.Jane L. Eisen, M.D.Jan Fawcett, M.D.Edna Foa, Ph.D.Amanda L. Gamble, Ph.D.Maryrose Gerardi, Ph.D.Christina M. Gilliam, Ph.D.Nicola D. Hanson, B.S.Richard G. Heimberg, Ph.D.Myron A. Hofer, M.D.Jonathan D. Huppert, Ph.D.Sarah Ketay, Ph.D.Ovsanna Leyfer, Ph.D.Jeffrey D. Lightfoot, Ph.D..Maria C. Mancebo, Ph.D.Michael J. Marcangelo, M.D.

Alexander C. McFarlane, M.D.Dean McKay, Ph.D.Phoebe S. Moore, Ph.D.Mary Morreale, M.D.Navin Natarajan, M.D.Laszlo A. Papp, M.D.Beth Patterson, B.Sc.N., B.Ed.Anthony Pinto, Ph.D.Kristin E. Pontoski, M.A.Holly J. Ramsawh, Ph.D.Ronald M. Rapee, Ph.D.Winfried Rief, Ph.D.Jerilyn Ross, M.A., L.I.C.S.W.William C. Sanderson, Ph.D.Casey Sarapas, B.S.Franklin R. Schneier, M.D.Steven J. Seay Jr., M.S.Ranjeeb Shrestha, M.D.William Simpson, B.S.Michael H. Stone, M.D.Manuel E. Tancer, M.D.Steven Taylor, Ph.D.Margo Thienemann, M.D.David F. Tolin, Ph.D.Christine Truong, B.Sc.Cynthia L. Turk, Ph.D.Oriana Vesga-Lopez, M.D.David Williams, Ph.D.Monnica T. Williams, Ph.D.Rachel Yehuda, Ph.D.Agustin G. Yip, M.D., Ph.D.Bruce Zahn, Ed.D.

xxi

Foreword

I am delighted, honored, and proud to comment on thesecond edition of the Textbook of Anxiety Disorders, amajor and most welcome contribution to the field. Imdelighted that the psychiatric community recognizesthe position of anxiety disorders as among the mostmisdiagnosed and undertreated, yet most prevalent andeconomically burdensome of all psychiatric syndromes.Im honored for the opportunity, on behalf of the Anx-iety Disorders Association of America (ADAA), to re-mark on this outstanding collection of contributions byworld-renowned experts at the leading edge of research,theory, and clinical knowledge. And Im proud that theanxiety disorders field is growing at such a rapid pacethat an updated edition, designed to reach a broader au-dience of health care professionals, is warranted.

When the ADAA was established nearly 30 years ago(as the Phobia Society of America), there was no anxi-ety disorders field. Not only didnt we have names forthe different disorders, we labeled just about everythinga phobia. The young man who spent hours each daywashing and rewashing his hands was said to have agerm phobia. Agoraphobia, without avoidance washow we diagnosed the young mother who had repeatedpanic attacks but continued to carry out her daily activ-ities. The soldier who returned from the front line whoavoided driving for fear of the flashbacks that occurredanytime he heard a loud noise on the road behind himwas said to have a driving phobia caused by shell shock.

In the late 1970s, following a CBS 60 Minutesprogram about phobias, thousands of people were re-lieved to learn that there was a name for what was ailingthemand that they were not alone. Still, they were em-barrassed to talk about their irrational fears, thoughts, or

behaviors. And when they sought help, they found lim-ited options. When the Phobia Society of America wasformed in 1979 by a small group of psychiatrists, psy-chologists, social workers, patients, and family members,myself included, its purpose was to find answers to thesequestions: How can we better understand these disor-ders? What can we do to help those suffering from them?

By 1990, a few years after the Diagnostic and Statis-tical Manual of Mental Disorders (DSM) put forth crite-ria for differentially diagnosing each distinct anxietydisorder, the organization had changed its name to theAnxiety Disorders Association of America to more ac-curately reflect the conditions it represents. AlthoughADAA is not planning to change its name again anytime soon, it has participated in the process of the de-velopment of the forthcoming DSM-V, and, as a stake-holder, it is eagerly looking forward to that editionspublication in 2012. The information in the new edi-tion of this textbook will help guide that revision, as wellas that of the International Statistical Classification ofDiseases and Related Health Problems, 10th Revision(ICD-10).

During the past few decades, research into the phe-nomenology, pathophysiology, and neurobiology of anx-iety disorders has exploded, offering people with anxietydisorders hope and help. The translation of neuroscience,which looks at what happens in laboratory animals andapplies the understanding of how the same mechanismswork in humans, has introduced new insights into theroot causes of anxiety, provided us with new and moreoptimal psychosocial and pharmacological treatments,and led to exciting breakthroughs in the interaction be-tween genes and the environment. But we have a long

xxii TEXTBOOK OF ANXIETY DISORDERS

way to go, especially with regard to understanding theonset of the disorders and their impact on special popu-lationswomen, children, adolescents, and the elderly.Posttraumatic stress disorder, common to all populations,presents an ongoingand growingglobal challenge.

The vision of the editors of the second edition of theTextbook of Anxiety Disorders to present health profes-sionals in a wide range of disciplines with the translationof neuroscience, as well as a broader understanding ofthe phenomenology of anxiety disorders, is reflected inthe well-considered organization of the book. The be-ginning chapters focus on the basic mechanisms of anx-iety disorders and are followed by a thorough review ofeach disorder addressed from multiple perspectives.The chapters covering the latest developments in phar-macological and psychosocial interventions for eachdisorder make the book particularly relevant for clini-cians in the medical field as well as psychologists, socialworkers, counselors, and other mental health profes-sionals involved in the treatment of anxiety disorders.Medical students and those in psychology, social work,and other mental healthrelated graduate programspreparing for clinical practice will also find this an ex-cellent teaching tool and reference guide. The final sec-tion of the book focuses on special populations and thesocial aspects of anxiety disorders, areas of particularrelevance to the efforts of ADAA to overcome stigma,to work toward the prevention, treatment and cure ofanxiety disorders, and to improve the lives of all peoplewho suffer from them.

For this invaluable resource we owe a debt of grati-tude to the editors: Dan J. Stein, M.D., Ph.D.; EricHollander, M.D.; and Barbara Olasov Rothbaum, Ph.D.,ABPP. Dr. Stein has made major contributions to the

understanding of the psychobiology and management ofanxiety disorders, especially in the areas of social anxietydisorder, obsessive-compulsive disorder, and posttrau-matic stress disorder. Dr. Hollander has significantlycontributed to the knowledge base of OCD and theOCD spectrum disorders through his pioneering re-search into the understanding of the basic neurobiologyof OCD, an expanded notion of repetitive behaviors,and the conceptualization of anxiety disorders.

The addition of Dr. Rothbaum, a clinical psycholo-gist and highly esteemed researcher, as an editor for thisedition broadens the books relevance to both the scien-tific and clinical communities. Dr. Rothbaums cutting-edge work in the application of virtual reality to thetreatment of anxiety disorders and her use of basiclearning mechanisms in exposure therapy have givenclinicians new weapons in their arsenal of effectivetreatments.

Thanks to the contributors to this book, we havea greater understanding of the root causes of anxietydisorders, proven treatments, and new hope for thosewhose lives have been compromised by persistent, irra-tional, chronic, or life-altering anxiety. The book will in-form and foster discussion. It is poised to influencehealth professionals in their understanding of anxietydisorders, enhance their clinical skills, and provide themwith the background to best communicate with theircolleagues, legislators, and the public that anxiety disor-ders are real, serious, and treatable. It is a major leap for-ward for the field.

Jerilyn Ross, M.A., L.I.C.S.W.Director, The Ross Center for Anxiety & Related Disorders

President and CEO, Anxiety Disorders Association of America

xxiii

Preface

Anxiety is one of the oldest of subjects. The phyloge-netic origins of anxiety date back to the origins of theanimal kingdom, and philosophers and thinkers havelong written about the centrality of anxiety to humanlife and experience. The experience of anxiety has aubiquity and a universality that extends across times andacross cultures.

At the same time, anxiety is one of the newest of sub-jects. It is only in the past few decades that scientists andclinicians have been able to develop rigorous diagnosticschemas, to appreciate the prevalence of different anxi-ety disorders, to understand their underlying psychobi-ology, and to develop effective pharmacotherapy andpsychotherapy interventions.

While the universality of anxiety and its disordersprovides this book with its justification, it is these newadvances that have often inspired our interest in theanxiety disorders and that provided the immediate im-petus to collect a series of contributions at the cuttingedge of anxiety disorder research and clinical practice.New advances are also the reason for this second editionof our original volume; we felt that many chapters werein need of updating, and that developments in the fieldrequired the text to be supplemented with new chapters.

A number of these advances are particularly worthemphasizing at the outset. First, it is not always appre-ciated that the anxiety disorders are not only among themost prevalent of the psychiatric disorders, but alsoamong the most disabling. Both the National Co-morbidity SurveyReplication and the World MentalHealth Survey found that taken together, the anxietydisorders are more common than either mood or sub-stance use disorders.

Furthermore, it has been estimated that one-third ofall costs of psychiatric disorders are due to the anxietydisorders; in particular, the anxiety disorders are associ-ated with high indirect costs. Although the high directcosts of disorders such as the psychotic disorders are ob-vious, the high indirect costs of the anxiety disorders areless so, and therefore require continued emphasis.

Unfortunately, however, the anxiety disorders con-tinue to be misdiagnosed and undertreated. Perhaps thevery universality of anxiety makes it more difficult forcaregivers to appreciate the morbidity of anxiety disor-ders, and for patients to seek help. Clinicians and advo-cacy groups have made important strides in increasingawareness, but much further work remains to be done.

On the other hand, the psychobiology of anxiety dis-orders is indisputably one of the most interesting andrewarding areas of contemporary medical research. Thespecific neuroanatomy, neurochemistry, cognitive dys-functions, and genetic and environmental contributionsto each of the anxiety disorders are gradually being out-lined. Data from disparate fields are being integratedinto powerful and sophisticated models.

Indeed, anxiety disorders provide researchers and cli-nicians a remarkable locus for integration. Animal mod-els of fear conditioning, for example, provide fascinatingparallels with clinical phenomena such as posttraumaticstress. Similarly, functional brain imaging has demon-strated how the pharmacotherapy and psychotherapy ofanxiety disorders are both able to normalize underlyingfunctional neuroanatomy, providing a unique opportu-nity for the integration of brain and mind.

In the remainder of this volume we include subsec-tions on each of the main anxiety disorders (including

xxiv TEXTBOOK OF ANXIETY DISORDERS

chapters on their phenomenology, psychobiology, phar-macotherapy, and psychotherapy). The introductoryand concluding sections also consider a number of the-oretical and clinical issues that cut across the differentanxiety disorders.

We would like to express our gratitude to the con-tributors who have updated their chapters or providedentirely new chapters for this second edition, to our col-

leagues who have helped support and guide us, to thepatients who have taught us about themselves, and toour families for their love and encouragement.

Dan J. Stein, M.D., Ph.D.Eric Hollander, M.D.

Barbara O. Rothbaum, Ph.D., ABPP

Part

I

Approaching the Anxiety Disorders

3 Chapter 1

History of Anxiety DisordersMichael H. Stone, M.D.

Anxiety goes back to our very beginnings. Perhaps be-cause of the very universality of anxiety as part of the hu-man condition, physicians in ancient times omitted itfrom their roster of mental illnesses. The Greeks of theclassical age had words for mania, melancholia, hysteria,and paranoia. (In fact, those are the Greek words that westill use today.) But they had no word for anxiety. Inmodern Greek, we confront the word anesuchia, whoseroot meaning is not quiet or not calm. The Romansin Ciceros time used the word anxietas, which indicateda lasting state of fearfulness, in contrast with angor,which signified a momentary state of intense fear, akinto our concept of panic. Angor also meant stranglingand derives from the verb angoto press something to-gether, to strangle. The idea of narrowness is anotherconnotation, as in the Latin angustia (narrowness), theFrench angoisse (anguisha more acute, paniclikestate), and the German angst (fear) and eng (narrow).The angr root in Indo-European languages also gaverise to our anger (akin to Old Norse angra: grief ) and an-gina (a term also used in Roman times to signify a crush-ing sensation in the chest and the accompanying dread).

Early Commentaries on Anxiety or Equivalent StatesIt is easy enough to understand the origins of our mod-ern word because anxiety is often accompanied by afeeling of closeness; a feeling of pressure on the chest,such that one can scarcely breathe; or a feeling of pres-sure on the abdomen (Littre and Robin 1858).

Berrios and Link (1995) pointed out that, althoughmany references to anxiety-like states are found in olderbooks such as Burtons (1621) Anatomy of Melancholy,the term anxiety was not used as such in psychiatric par-lance until later. Instead, the individual symptoms andmanifestations were considered as separate diseases orconditions. That is, the difficulty breathing while in astate of anxiety would be ascribed to some pulmonaryabnormality, what we call butterflies in the stomachwould be understood as some gastric malady, and thedizziness that may accompany intense anxiety might bedescribed as the condition of vertigo and seen as afunction of a middle-ear problem. Symptoms of thissort would be manifestations of what Berrios and Link(1995) called the objective aspects of anxiety. These in-clude what we now call the psychosomatic illnesses thatcan arise in the context of intense anxiety, such as ab-dominal pain, palpitations, hot flushes, and breathless-ness. The contrasting subjective aspects are those thatadhere more closely to modern conceptions of anxietystates or disorders, such as feelings of terror; pressingworries; phobias; stage fright; obsessive ruminationsabout dirt, disease, and death; and experiences of de-personalization or derealization. Burton (1621) hintedthat some connection probably existed between the dis-turbances of the mind and those of the body:

The Minde most effectually workes upon the Body,producing by his passions and perturbations, miracu-lous alterations; as Melancholy, despaire, cruell dis-eases, and sometimes death itselfe. Inso much, that it

4 TEXTBOOK OF ANXIETY DISORDERS

is most true which Plato saith in his Charmides: omniacorpora mala ab anima procedere: all the mischiefs ofthe Body, proceede from the Soule. (p. 78)

But nowhere does Burton mention the term anxietyitself.

Anxiety, as we understand it, was often conflatedwith the concept of melancholia in medieval times andduring the Renaissance. Just as contemporary cliniciansseldom encounter seriously depressed patients who arenot also anxious to a significant degree, melancholicpersons in bygone times were simultaneously consid-ered pathologically anxious. One common form of thismixed state was (and still is) lovesickness. Presumably,there was something special about lovesickness (ordoubting-with-compulsions) that would attract the at-tention of a physician: persons with these conditionswere dysfunctional. The lovesick nephew, for example,was seen as wasting away in bed, lacking appetite andeven the will to live. Someone expressing the sameworry repeatedly and showing some repetitive behavior(such as hand washing) would strike physicians and lay-persons alike as different from an ordinary person.What was missing, and what did not become commonmedical currency until the nineteenth century, was theawareness that anxiety (of this more than normal sort)was the red thread that ran through a variety of condi-tions: lovesickness, obsessive-compulsive symptoms,fainting spells, hypochondriasis, and the like. At thesame time, these anxiety disorders, as we would callthem, usually fell short of necessitating institutionalcare. Hence, the medical literature from the first printedbooks (mid-fifteenth century) until this red threadwas discovered was very sparse in its mention of thesedisorders.

Among the descriptions of such conditions in theseventeenth century was that of the English moral-tractwriter Richard Younge. In his sketches of mental abnor-malities (Younge 1638) are some that inspired the char-acterology of Richard Flecknoes Enigmaticall Charac-ters, written a generation later (Flecknoe 1658). Bythen, as Hunter and Macalpine (1963) noted, psychiat-ric labels had come to be attached to these abnormalstates. Flecknoe wrote of anxiety states in which onetroubles herself with every thing, or the irresolute per-son (the contemporary obsessive-compulsive person),who hovers in his every choice like an empty Ballancewith no weight of Judgment to incline him to eitherscale. ..when he begins to deliberate, he never makes anend (Hunter and Macalpine 1963, p. 116).

A Cross-Cultural PerspectiveAttention by the medical community to anxiety disor-ders was not confined to the West. In many instances,however, the cultural differences that affected how anx-iety was understood, experienced, and treated were pro-found, differing substantially from conceptions familiarto those of a European or American background.

The eleventh-century Persian physician Avicenna(Ali al-Husayn ibn Sina: 9801037) wrote an encyclo-pedic treatise called the Canons of Medicine, covering allconditionsincluding mental conditions such as maniaand melancholy. As for anxiety, the story is told (Hajal1994) of how Avicenna was able to diagnose and cure acase of combined depression and anxietyknown aslovesickness (ishk)in a young nobleman who wasdeeply in love with a woman he thought was forbid-den. He had fallen into a state of intense anxiety andmelancholy. Relying on fluctuations in the mans pulseas Avicenna mentioned locales nearer and nearer towhere the woman lived, the physician diagnosed thatthe man was, much to his chagrin, in love with hiscousin. His uncle the king considered a union of cousinslegitimate, however, and with that blessing the youngman quickly recovered.

In ancient China, emphasis was placed on the sup-posed correspondence between certain emotions andthe bodily organs that were deemed especially vulnera-ble to these emotions. Excess anger, for example, wasconsidered harmful to the liver; excess happiness, to theheart. Fear was deleterious to the kidney; sadness, to thelungs (perhaps because sighing is linked with sadness).As in the case of lovesickness, anxiety and depressionoften occur together, so it is not surprising that the usualChinese term for anxiety to this day is yu-l; the firstcharacter designates grief, the second character, care oranxiety. Related words express the notion of anticipa-tion (reminiscent of Freuds concept of anticipatory anx-iety): l-huan (to take precautions against calamity) andl-chi (to anticipate). The main Japanese term for anxi-ety is the same as in Chinese, using the same characters,though pronounced a bit differently: yu-ryo, signifyinganxious-thought.

Traditional Chinese medicine aims to treat anxietythrough the kidney, just as it would treat anger throughthe liver and mania via some intervention involving theheart. Even now, one of the commonest diagnosticterms in psychiatric practice in China is neurastheniano longer used in the West. Patients so diagnosed aregenerally rediagnosed with anxiety or depression, or

History of Anxiety Disorders 5

both, when evaluated according to ICD-9 criteria(Zhang 1989). An important variant of neurasthenia incontemporary China is shenkui (literally, kidney defi-ciency), supposedly brought about by excessive mastur-bation and leading to lassitude and weakness. The anx-iety component consists of the worry that this habit maydeplete a young mans yang, or masculine force (Stone1997a, p. 419). Still another variety is called brain neur-asthenia, brought about by excessive studying (nao-shenjing shuai-ruo), and associated with dizziness, in-somnia, and poor concentration. What these examplesshow is that situations that, worldwide, typically causeanxiety are accompanied by varying somatic and psychicsymptomsshaped by the different cultures withinwhich the situations (exam-fear, love-worries) occur(see Chapter 39, Cultural and Social Aspects of Anxi-ety Disorders, in this volume).

In Korea there is an anxiety-related condition towhich middle-aged women are particularly prone whentroubled by marital unhappiness or domestic violence.They develop hwa-byung, in which anxiety, depression,and a sense of burning in the abdomen are combined(the term means fire disease). In bygone times, the con-dition was often treated by a village shaman, who in ef-fect exorcised the offending spirit (which we wouldidentify as the unexpressed anger of the patient). Now-adays, with increasing westernization, treatment is moreapt to be antianxiety medication and psychotherapy.

Eighteenth-Century Impressions About AnxietyAt some point in the early eighteenth century, the termanxiety began to be used in medical writing about men-tal illness. We can hardly speak about psychiatry yetbecause this word did not come into medical parlanceuntil Johann Reil coined it in 1808. Use of the termanxiety also meant, in effect, that a distinction was beingestablished between the normal levels average peopleexperienced after disappointments in love, financialworries, and so on, and the excessive levels noticeable inpersons who overreacted grossly to similar life events (asLePois [1618] had commented on a century earlier).

In England, Sir Richard Blackmore (16531729), ina treatise on vapours, advocated pacifick medicinesfor what today we would call anxiety states and othersignificant psychological disturbances: If Inquietudebe the Distemper, Quiet must be the Cure (Blackmore1725). The old term vapours was itself analogous insome respects to our concept of anxiety disorders: Aris-

totle had contended, for example, that the brain con-densed vapors that emanated from the heart and thatvapors were involved in various nervous (especiallyhysteric) states (Stone 1997a). Blackmore believed thatopiates in moderation were helpful in hypochondriacaland hysteric cases and did not lead to loss of appetite ormental dullness.

The first psychiatric textbook in English was writtenby William Battie (17031776), director of BethlemHospital in London, England, and later (in 1751) thefounder of St. Lukes Hospital, also in London.

Although his work concentrated on the more grave(we would say psychotic) disorders necessitating hospi-talization, he distinguished between madness andanxiety, writing of the latter in this vein:

It may not be improper to take some notice of thosetwo other disorders .. .which were excluded from ourdefinition of Madness, viz., praeternatural Anxiety orSensation too greatly excited by real objects, and itscontrary Insensibility or Sensation not sufficiently ex-cited by real objects. Madness in its proper sense[is] very often preceded by or accompanied with thefirst and often terminates in the second of these twodisorders. Whatever may be the cause of Anxiety, itchiefly discovers itself by that agonizing impatienceobservable in some men of black November days, ofeasterly winds, of heat, cold, damps, etc. (Battie 1758,p. 33)

On the theoretical plane, Battie adhered to the viewthat anxiety was to be understood mainly in terms of thebody, more so than of the mind, insofar as it representedan excess of sensation. Batties awareness that manydeluded persons (those with madness) also at timesexperienced anxiety, whereas many other personsshowed anxiety without ever experiencing madnessconfused some of his colleagues, such as James Vere(17001779). Vere (1778) was a merchant of Londonand a governor of the Bethlem Hospital. In his view,nervousness (which we can read as anxiety) could be un-derstood as the outcome of an internal war or conflictbetween the lower order of instincts and the moralinstincts. The lower order of instincts involved thepreservation and continuance of existence (which wemight read as sex and aggression). This strikes the mod-ern ear as very much in keeping with the Freudian tri-partite model of the mind, in which the ego is seen asmediating between the impulses stemming from the idand the prohibitions imposed by the superego (Freud1923/1961). In a similar prelibation of Freudian theory(here, the aspect dealing with the pleasure-pain princi-


ple), Vere also spoke of the two great principles whichactuate all animated bodies: appetite and desire [versus]aversion and dislike.

The Scottish neurologist Robert Whytt (17141766) focused, as Battie had done, on sensation and theperipheral nervous system in his writings on hysteria,hypochondriasis, and the nervous disorders (Whytt1765). He mentioned that the coats of the nerves maybe obstructed, or inflamed, compressed by hard swell-ings, or irritated by acrid humours (p. 85), and viewedabnormalities of this sort (perhaps because of his neu-rological background) as the root causes of the minor(i.e., nonpsychotic) afflictions he worked with. Whyttalso wrote of nervous exhaustionsimilar to the nine-teenth-century concept of neurasthenia. Allusions towhat we would consider anxiety are found in Whyttscomments on palpitations, in which he states, In thosewhose nervous system is easily moved, any sudden andstrong passion, but especially fear, will produce palpita-tions, and an irregular motion of the heart, by renderingit more irritable (p. 286).

The relationship between anxiety and nightmareswas touched on in a treatise on the incubus by John Bondin 1753. The idea of an incubus as a causative factor innightmares stemmed from the belief that some spirit orghostly person crept in during the night and lay uponthe sleeper, so as to constrict the chest and breathingleading to a sense of suffocation, side by side with a ter-rifying dream of being either crushed or (in the case ofa woman) sexually violated by the (male) incubus orephialtes, as many authors of this period called it. Sleep-ers thus set upon feel they are about to diebut as Bond(who was himself prone to nightmares) stated, As soonas they shake off that vast oppression, they are affectedwith a strong palpitation, great anxiety, languor, and un-easinesswhich symptoms gradually abate, and aresucceeded by the pleasing reflection of having escapedsuch imminent danger (p. 3). Further on, Bond givesexamples of women who experienced nightmares in thetwo or three days before their menses, complaining ofanxiety and oppression in the breasts for several days af-ter the menstrual flow began (p. 48). Here, there is anearly allusion to premenstrual tension. But in the morecommon form of nightmare, Bond pictured the night-mare as causing the anxietywhereas we would tend tothink that certain anxiety-engendering life events fromthe previous day were the main causative factors. An-other way to understand the concept of the incubus is toreflect once again on the root meaning of anxiety as re-ferred to above: the (distressing) mental accompani-

ment of being strangled or suffocated by a weight press-ing on the chest.

In France, intense anxiety states were mentioned inthe medical text of Boissier de Sauvages (1752), al-though not yet with the terms anxit or angoisse. Hespoke, for example, of panophobia, a generalized state ofanxiety that might express itself by turns as pavor noc-turnus, intense shaking of the body, insomnia, or feel-ings of terror arising from the working of the imagina-tion (p. 240). The concept of panophobia was echoed acentury and a half later in Ribots term pantophobia.

Thus far, as we have seen, the medical practitionersin the field of mental illness (they could be called alien-ists at this stage, but not yet psychiatrists) concentratedon patients with delusions and other severe disorders re-quiring institutional care. The less serious disorderswere seen as abnormalities of the nerves, or of the brainto which the nerves were connected. This was a verybiological view of mental illness. Although there wassome awareness of the psychological underpinnings ofsome of these afflictions, these were seldom placed inthe hierarchy of causative factors. One has the impres-sion that ordinary people themselves were less aware ofthe psychological, interpersonal stresses that underlaytheir illnesses, and that they tended to somatizepartlybecause they lacked awareness, but also because somaticconditions were the only afflictions that their physicianswere equipped to hear about and deal with. Contempo-rary conditions such hwa-byung (burning in the stom-ach) among Koreans (Stone 1997a, p. 423) seem al-together analogous to the fainting spells of anxiouswomen in the eighteenth and nineteenth centuries, whohad little opportunity to escape psychologically intoler-able situations except by developing somatic conditions.

This emphasis on the nerves is still discernible inthe writings of the celebrated Scottish physician Wil-liam Cullen (17101790), who coined the term neurosis:I propose to comprehend, under the title of Neurosis,all those praeternatural affections of sense and motion,which are without pyrexia, and all those whichdepend upon a more general affection of the nervoussystem (Cullen 1807, p. 387).

The Nineteenth Century: The Early YearsThe early years of the nineteenth century witnessed ashift within the mental health field from attention tothe somatic causes or accompaniments of mental illnessto the possible psychological causes. The German Ro-


mantic period was in full swing, having been energizedby works such as Goethes The Sorrows of Young Werther(1774). In Goethes tale of hopeless love for an unavail-able woman, the protagonist s suicide precipitated awave of suicides in Europe, earning the author the con-tumely of the English vicar Charles Moore (17431811), whose magnum opus on suicide (Moore 1790)condemned Goethe for his lovesick tale.

Nevertheless, during this time (which lasted untilabout 1840), the first lengthy biographical sketcheswere writtenin the medical literatureabout theanxieties, conflicts, and general psychological problemsof people in everyday life. Among the earliest of suchsketches were those of Christian Spiess (1796) in Ger-many, John Haslam (1809) in England, and the directorof Berlins Charity Hospital, Karl Ideler (1841).

These influences were not felt in America untilsometime later. Cullens pupil Benjamin Rush (17461813), from Philadelphia, Pennsylvania, was writing inhis psychiatric text in a still very somatic vein aboutanxiety disorders. The objects of fear are of two kinds,he remarked: the reasonable (death and surgical oper-ations) and the Unreasonable (these are, thunder, dark-ness, ghosts, speaking in public, sailing, riding, certainanimals, particularly cats, rats, insects and the like)(Rush 1812, p. 325). As for the one anxiety disorder thatis easily recognizable to us as a type of social anxiety,speaking in public, Rush did not elaborate more than tosay, The fear from speaking in public was always obvi-ated by Mr. John Hunter, by taking a dose of laudanum[an opiate] before he met his class every day (p. 332).The year after Rushs book appeared, Landre-Beauvais(1813) in France used the term angoisse to designateanxiety states, defining it as a certain malaise, restless-ness, excessive agitation that could accompany eitheracute or chronic conditions and either psychological orsomatic expressions of anxiety (Berrios and Link 1995,p. 546). This state of intense fearfulness was still seen asan element in the clinical picture of melancholia (Geor-get 1820; Pinel 1801). Another label that indicated acondition involving severe anxiety was monomaniawith fear. To show the equivalence of this term withour concepts of anxiety disorder, Alexander Morrison(1826) in his lectures on mental diseases appended etch-ings of typical patients. The caption to Plate VI reads asfollows: This plate is intended to give an idea of partialinsanity with fear, what has been termed Panaphobia.The subject is female, although, from her dress, sherather gives the idea of a male. Delusive fear of every ob-ject and person keeps her in a state of perpetual distress:

it is necessary to watch her closely, to prevent her fromcommitting suicide (p. 136).

The phrase anxiety of mind appeared shortly after-ward in a book by the English physician Charles Thack-rah (1831). Writing about the tribulations peculiar toeach of the five social classes he outlined, he com-mented that the health of doctors is impaired particu-larly by anxiety of mind. Thackrah ascribed this vul-nerability to the physicians special need for study andresearch and (worst of all) for making night calls.

Although, in general, anxiety and anguish were bythen seen as manifestations of psychiatric disturbancesof a severity intermediate between psychosis (mad-ness, lunacy, or insanity) and normalcy, Prichard(1835) nevertheless claimed that care and anxiety, dis-tress, grief, and mental disturbances were the mostcommon causes of insanity.

Jules Angst (1995) mentioned a German physician,Otto Domrich, who wrote in the first half of the nine-teenth century about anxiety attacks. These consisted ofa combination of anxiety and cardiopulmonary symp-toms, such as might be induced (for example, in thepresent-day description of posttraumatic stress disor-der) by the terror of the battlefield.

Implicit in my comment above about German Ro-manticism is that advances in theory about anxiety didcome mostly from German-speaking authors through-out the first half of the nineteenth century. The Germanschool went beyond the empiricism of the British andthe French, who were still dwelling on the state of thenerves of anxious persons (and on the various ano-dynes that might soothe those nerves) rather than onthe particularities of the individual persons who experi-enced various forms of anxiety. Friedrich Beneke(17981854), for example, argued that certain ideas orattitudes of mind could be symbolized within psycho-somatic reactions (Beneke 1853). Along similar lines,Baron Ernst von Feuchtersleben (18061849) stressedthe role of conflict, as Vere had done 50 years earlier, ascentral to the understanding of mental illness (vonFeuchtersleben 1838, 1845). Again, the conflict wasseen specifically as the battle between ones irrationalimpulses and ones more reasonable wishes and expec-tations. As to his psychosomatic views, von Feuchter-sleben understood that intense anxiety and grief couldlead to organic conditions of the heart and the digestivesystem (Berrios and Link 1995, p. 548). We also mustcredit the Viennese baron with a thought that may beseen as prefiguring Freuds famous dictum about freeingthe psychoanalytic patient from neurotic misery by


making the unconscious consciousin effect, helpingthe patient to master the anxiety from hidden sources byenabling those sources to reach the level of awareness.

We should also acknowledge the contributionof Jean-Etienne Esquirol (17721840), who did notwrite on the topic of anxiety per se but did provide de-tailed clinical examples of what we now call obsessive-compulsive disorder (OCD). Esquirols (1838, p. 62)descriptions served as the inspiration for the even moredetailed descriptions of Henri Le Grand du Saulle(18301886), one of which I had translated in an earliercommunication (Stone 1997b). Here, I give only briefportions taken from the description of one of EsquirolsOCD patients:

Miss F., age 34, was raised in a merchant householdfrom her earliest days. She feared that she would dowrong to others, and later on, when she handled thepayments and receipts, feared that she would make amistake in giving too little change to a customer.Back in her parents shop, she would fear that, in re-turning change to a customer, she might have retainedin her fingers something of value. She knew heranxiety was absurd and ridiculous but could donothing to control her behavior. She ended up shak-ing her hands vigorously after touching nothing, tomake sure that nothing stuck to her fingers that didntbelong to her. (Esquirol 1838, Vol. 2, pp. 6364) (mytranslation)

The Nineteenth Century: The Later YearsBy the second half of the nineteenth century, there wasmore widespread recognition that anxiety, in its moreintense or persistent forms, deserved its own placewithin psychiatric nosology. As was typical of the Frenchschool, anxiety was seen as part of a three-stage pro-cess, which began with inquietude, progressed to anx-iety, and might end with anguish (angoisse) (Littre andRobin 1858). Feelings of closeness and difficultybreathing were noted in descriptions of both anxietyand anguish.

In Germany, Wilhelm Griesinger (18171868) sawmental disease and somatic disease as one; neuropathol-ogy and psychiatry were in essence the same field. Herealized that not all behavior was consciously deter-mined, and acknowledged the importance of tempera-ment and personality. Although he thought that mentaldisease must stem from abnormalities of the brain cells(and thus had an organic basis), he nevertheless en-dorsed the idea from his Romanticist predecessors that

strong affects could induce mental illness. Such illnessmight come about, in Griesingers (1861) view, becauseof conflicts involving the repression (Verdraengung) ofsexual urgesa Freudian concept expressed a genera-tion before Freud. Griesinger estimated that one in tenpatients who developed a psychosis (insanity) did sowith acute fear as the inciting agent.

A similar theory was espoused by Heinrich WilhelmNeumann (18141884), a contemporary of Griesinger.Neumann (1859) saw mental illness as partaking of adynamic process in which under normal circumstances aperson succeeds in his or her development toward afreedom gained through self-mastery. In pathologicalcircumstances the perturbations of the drives, especiallythe sexual ones, disturb ones harmony. When the drivescannot be satisfied, anxiety appears. Furthermore, ifcertain life functions are threatened, the instinctualneeds are apt to express themselves in consciousness asperceptions (Neumann used the Greek word aistheses)or calls that make the person aware of impending dan-ger (Beauchesne 1781, p. 51). Neumanns theory antic-ipated Freuds reworking of his anxiety theory in 1923,wherein he spoke of signal anxiety.

Psychiatry in the second half of the nineteenth cen-tury remained biologically oriented, and this was evenmore true in France than in Germany. Benedict Morel(18091873), to whom we owe the concept of dmenceprcoce (Morel 1860) (which gave rise to the later con-cepts of dementia praecox and schizophrenia), believedthat both the psychological and the somatic (subjectiveand objective) expressions of anxiety could lead topathological changes in the autonomic nervous system(Berrios and Link 1995, p. 549).

Le Grand du Saulle (1878), a prominent and prolificpsychiatrist at the Bictre Hospital in Paris, France,wrote a monograph on the peur des espaces (fear ofspaces) based on Westphals (1872) article on agora-phobia. Le Grand du Saulle preferred this admittedlymore vague designation rather than the term agorapho-bia that the German school preferred because althoughone may see now and again that these patients fear openspaces, they may experience the fear at the theater, atchurch, on an elevated storey of a building, or while in-side near a window giving out to a large courtyard, or ona bus or boat or a bridge (p. 6, my translation).

In a separate monograph of 1875 entitled La folie dudoute avec dlire du toucher (doubting mania, with dreadof being touched), Le Grand du Saulle gave clinicaldescriptions of persons with what we now know as ob-sessive-compulsive disorder, as well as with related anx-


iety conditions such as generalized anxiety, or a tor-menting conviction of sinfulness (in otherwise timidand well-behaved persons) (Le Grand du Saulle 1875).One woman in her mid-20s, for example, became ob-sessed, as she walked along the streets, that someonemight hurl themselves from a window and land in frontof her. She would ponder, Would it be a man or awoman, would the person be killed or just wounded,would there be blood on the sidewalk, should I call forhelp or run away, would I be held responsible or wouldpeople believe my innocence? In another case, a 30-year-old man was obsessed with colors and numbers.He would ask why trees are green, why brides wearwhite, why soldiers have red trousers, etc., but he wouldalso find himself counting the objects in a room wherehe was visiting, telling his host, You have 44 books onyour table, and your vest has seven buttons, then apol-ogizing: Excuse me, its involuntary, but I feel I mustcount things (p. 12). He felt extremely anxious aboutthis tendency and said he would be willing to do any-thing to achieve tranquility. In still another case, an 18-year-old orphan girl adopted into a wealthy family wastormented by the memory that she had once laughed inthe church where she had her first communion, and bythe recollection that she had withheld from the priest atconfession one of her sins. As a penitence for thesepeccadilloes she decided to starve herself, losing consid-erable weight in the process. She was also afraid to sleep,lest she die unshriven. The cure that Le Grand duSaulle hit upon was to have her parents provide her witha companion who would sleep in the room with her.This seemed to work, and the girl regained her equa-nimity. But there is not a hint in any of his vignettesabout dynamics: what may, in a psychological way,have predisposed these patients to manifest the anxioussymptoms for which they sought help. Le Grand duSaulle viewed these conditions as exaggerations of con-science, as distinct from melancholic or persecutory con-ditions, in which sadness and suspiciousness are exag-gerated. His ideas about etiology were limited to hisobservations that these anxiety disorders (nvroses, inhis terminology) tended to show up first during puberty.Perhaps a morbid heredity played a role (p. 60), giventhat, in his observations, many such patients had rela-tives with various forms of mental illness. Also impli-cated were certain physical diseases: typhoid, cholera, aswell as habits, such as habitual onanism. Yet all ofthese anxiety disorder patients could give good accountof themselves and their symptomsthey were not psy-chotic. The only other clue he offered concerning eti-

ology was that women seemed more prone to doubtingfolly than men, and that those in the upper socialclasses were more vulnerable than those less well off.

Although Le Grand du Saulle (1878) mentionedthat psychological causes had been cited by other au-thors (too vivid emotions of a person sad by nature, anunexpected fright, the sudden death of a loved one, thegood luck to have escaped a great danger, excessive in-tellectual efforts, insufficient sleep, or sexual excess[p. 31]), he favored either medical (somatic) rather thanpsychological factors, or, as previously mentioned, ad-verse hereditythe latter view endorsed also by Dago-net (1894).

Earlier, Dagonet (1876), a professor of psychiatry inStrasbourg, France, had described several forms of anx-iety under the broad heading of lypemanie (Esquirolsterm for depression, stemming from the Greek lupeo,to grieve). He characterized hypochondriasis (lype-manie hypochondriaque) as beginning with mild symp-toms, which progress in the usual three stages custom-ary in all French nineteenth-century psychiatric texts.The patient is anxious [inquiet], preoccupied, and be-gins to experience fears concerning his health; he in-spects his body minutely, . ..observes scrupulously all therules of hygiene; he reads books on medicine and is mosteager to speak with physicians about his condition(p. 25, my translation). Dagonet also discussed lype-manie anxieuse (anxious depression), also known aspanophobia, angoisse morale (anguished mood, or in Ger-man, Gemtsbeklemmung, or angst). Dagonet s casedescriptions were those of a serious disorder, midwaybetween our concept of generalized anxiety disorder andOCD, bordering on delusion. The clinician encoun-tered as the patients predominant symptoms les an-goisses, les inquietudes vagues, les terreurs, des conceptionserrons, et un dlire plus ou moins systematis (p. 239)(feelings of dread, vague anxieties, terror, false ideas,and more or less systematized delusory ideas). In thelengthier example provided by Dagonet, the patient hada mentally ill grandmother, uncle, and five cousins (allby that uncle), which suggested to Dagonet that hered-ity was the principal causative agent.

Berrios and Link (1995, p. 551) gave a description ofvertigo, written by Leroux (1889) for a medical encyclo-pedia, which could serve well as a defining example ofpanic attack. In this connection, Berrios credited LeGrand du Saulle with realizing that the patient withvertigo did not have an inner-ear malady, as Benediktwas still suggesting in 1870, but was more likely trou-bled by a fear of falling.


The panophobia, or lypemanie anxieuse, of which theEuropean psychiatrists of the period were speakingsimilar to generalized anxiety disorderwas given thename neurasthenia (a weakness of the nerves) by theAmerican neurologist George Miller Beard (18391883). Beard enjoyed considerable fame during hislifetime for his application of electrical treatmentsvoltaic-galvanic stimulation or faradic stimulationto the cure of neurasthenia (Beard 1880; Beard andRockwell 1875). The popularity of Beards method inthe waning years of the century can hardly be overesti-mated.

The neurasthenia concept was so popular that manymental health practitioners placed all types of anxiety-related conditions in this broad category. SigmundFreud (18561939) objected to this tendency: It can benothing but a gain to neuropathology if we make an at-tempt to separate from neurasthenia proper all thoseneurotic disturbances in whichthe symptoms are morefirmly linked to one another than to the typical symp-toms of neurasthenia (such as intracranial pressure, spi-nal irritation, and dyspepsia with flatulence and consti-pation) (Freud 1895/1962, p. 90). Freud went on todescribe anxiety neurosis, a term first published in the1895 paper, although he had used it in letters to Wil-helm Fliess two years earlier. Freud gave credit to EwaldHecker (1893) for originating the concept (Freud was atfirst unaware of Heckers paper), but Hecker had notgone so far as to discriminate between anxiety neurosisand neurasthenia, as Freud was now about to do. Theclinical picture was composed, as Freud outlined, of thefollowing elements: 1) general irritability; 2) anxious ex-pectation (Freud gave an example of a woman who fearsthat her husband has pneumonia every time she hearshim cough), which may als

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