APA Handbook of Psychopathology [1] 2017033373, 9781433828362, 1433828367

Volume 1: Psychopathology: Understanding, Assessing, and Treating Adult Mental Disorders

271 10 8MB

English Pages [813] Year 2018

Report DMCA / Copyright

DOWNLOAD PDF FILE

Table of contents :
I. Issues in Understanding Adult Psychopathology

Introduction to Understanding Psychopathology
James N. Butcher and Jill M. Hooley

History of Developments in Understanding Abnormal Behavior
German E. Berrios and Ivana S. Marková

Diagnosis and Classification of Psychopathology
Thomas A. Widiger and Cristina Crego

Examination of Neurological and Neuropsychological Features in Psychopathology
Colleen E. Jackson and William P. Milberg

Behavioral Genetic Insights on the Development of Psychopathology
Matt McGue, Gretchen Saunders, and Irving I. Gottesman

Sociocultural Factors in Psychopathology
Fanny M. Cheung and Winnie W. S. Mak

Understanding Psychopathology in Immigrant Populations
Giselle Hass

II. The Role of Assessment in Psychopathology

Evaluating Psychopathology With Personality Assessment Instruments
Robert E. Erard, David S. Nichols, and Alan Friedman

Neuropsychological Assessment
Carlton Gass

Understanding Functional Magnetic Resonance Imaging
Zachary P. Infantolino, Jessica I. Lake, and Gregory A. Miller

Assessing Psychopathology in High Risk Occupations
James N. Butcher, Chris M. Front, and Deniz S. Ones

Assessment of Psychopathology in Older Adults
Julie A. Lutz, Jarred V. Gallegos, and Barry A. Edelstein

Integrating Clinical Information and Developing Effective Reports
Marvin W. Acklin

III. Clinical Manifestations of Psychopathology

Neurocognitive Disorders
Maya Yutsis, Allyson C. Rosen, and Gayle K. Deutsch

Schizotypy, Schizotypic Psychopathology, and Schizophrenia: Understanding the Nature, Basis, and Manifestation of the Schizophrenia Spectrum
Mark F. Lenzenweger

Stress and its Sequelae: Depression, Suicide, Inflammation, and Physical Illness
George M. Slavich and Randy P. Auerbach

Mood Disorders
Diego A. Pizzagalli, Alexis E. Whitton, and Christian A. Webb

Anxiety Disorders
Thomas L. Rodebaugh, Jaclyn S. Weisman, and Natasha A. Tonge

Obsessive-Compulsive and Related Disorders
David F. Tolin and Kristen S. Springer

Substance-Related and Addictive Disorders
Shosuke Suzuki and Hedy Kober

Eating Disorders
Pamela K. Keel

Somatic Symptom and Related Disorders
Michael Witthöft, Maria Gropalis, and Florian Weck

Personality Disorders: Current Scientific Status and Ongoing Controversies
Scott O. Lilienfeld and Robert D. Latzman

IV. Treatment Considerations in Psychopathology

Psychopathology and Risk of Suicide
Brianna J. Turner, Evan M. Kleiman, and Matthew K. Nock

Incorporation of Therapeutic Assessment Into Treatment With Clients in Mental Health Programming
Filippo Aschieri, Francesca Fantini, and Stephen Edward Finn

Treatment of Psychopathology in Survivors of Torture
Solvig Ekblad, James M. Jaranson, and Marianne C. Kastrup

Cognitive–Behavioral Couple-Based Interventions for Relationship Distress and Psychopathology
Melanie S. Fischer and Donald H. Baucom

Families and Mental Disorders
Jill M. Hooley and David J. Miklowitz

Effectiveness of Psychotherapy
Kim de Jong and Robert J. DeRubeis

V. Ethical and Legal Issues in Psychopathology

Ethical Clinical Practice: Negotiating a Whole Lot of Gray in a Wise Way
Janet L. Sonne and Jennifer L. Weniger

Forensic Mental Health Practice
Harold J. Bursztajn and Stanley L. Brodsky
Recommend Papers

APA Handbook of Psychopathology [1]
 2017033373, 9781433828362, 1433828367

  • 0 0 0
  • Like this paper and download? You can publish your own PDF file online for free in a few minutes! Sign Up
File loading please wait...
Citation preview

Copyright American Psychological Association. Not for further distribution.

APA Handbook of

Psychopathology

APA Handbook of Psychopathology: Psychopathology: Understanding, Assessing, and Treating Adult Mental Disorders, edited by J. N. Butcher and J. M. Hooley Copyright © 2018 American Psychological Association. All rights reserved.

Copyright American Psychological Association. Not for further distribution.



APA Handbooks in Psychology® Series

APA Addiction Syndrome Handbook—two volumes Howard J. Shaffer, Editor-in-Chief APA Educational Psychology Handbook—three volumes Karen R. Harris, Steve Graham, and Tim Urdan, Editors-in-Chief APA Handbook of Behavior Analysis—two volumes Gregory J. Madden, Editor-in-Chief APA Handbook of Career Intervention—two volumes Paul J. Hartung, Mark L. Savickas, and W. Bruce Walsh, Editors-in-Chief APA Handbook of Clinical Geropsychology—two volumes Peter A. Lichtenberg and Benjamin T. Mast, Editors-in-Chief APA Handbook of Clinical Psychology—five volumes John C. Norcross, Gary R. VandenBos, and Donald K. Freedheim, Editors-in-Chief APA Handbook of Community Psychology—two volumes Meg A. Bond, Irma Serrano-García, and Christopher B. Keys, Editors-in-Chief APA Handbook of Comparative Psychology—two volumes Josep Call, Editor-in-Chief APA Handbook of Counseling Psychology—two volumes Nadya A. Fouad, Editor-in-Chief APA Handbook of Ethics in Psychology—two volumes Samuel J. Knapp, Editor-in-Chief APA Handbook of Forensic Neuropsychology—one volume Shane S. Bush, Editor-in-Chief APA Handbook of Forensic Psychology—two volumes Brian L. Cutler and Patricia A. Zapf, Editors-in-Chief APA Handbook of Giftedness and Talent—one volume Steven I. Pfeiffer, Editor-in-Chief APA Handbook of Human Systems Integration—one volume Deborah A. Boehm-Davis, Francis T. Durso, and John D. Lee, Editors-in-Chief APA Handbook of Industrial and Organizational Psychology—three volumes Sheldon Zedeck, Editor-in-Chief APA Handbook of Men and Masculinities—one volume Y. Joel Wong and Stephen R. Wester, Editors-in-Chief APA Handbook of Multicultural Psychology—two volumes Frederick T. L. Leong, Editor-in-Chief APA Handbook of Nonverbal Communication—one volume David Matsumoto, Hyisung C. Hwang, and Mark G. Frank, Editors-in-Chief APA Handbook of Personality and Social Psychology—four volumes Mario Mikulincer and Phillip R. Shaver, Editors-in-Chief APA Handbook of Psychology and Juvenile Justice—one volume Kirk Heilbrun, Editor-in-Chief APA Handbook of the Psychology of Women—two volumes Cheryl B. Travis and Jacquelyn W. White, Editors-in-Chief APA Handbook of Psychology, Religion, and Spirituality—two volumes Kenneth I. Pargament, Editor-in-Chief

Copyright American Psychological Association. Not for further distribution.

APA Handbook of Psychopathology—two volumes James N. Butcher, Editor-in-Chief APA Handbook of Research Methods in Psychology—three volumes Harris Cooper, Editor-in-Chief APA Handbook of Sexuality and Psychology—two volumes Deborah L. Tolman and Lisa M. Diamond, Editors-in-Chief APA Handbook of Testing and Assessment in Psychology—three volumes Kurt F. Geisinger, Editor-in-Chief APA Handbook of Trauma Psychology—two volumes Steven N. Gold, Editor-in-Chief

Copyright American Psychological Association. Not for further distribution.

APA Handbooks in Psychology

Copyright American Psychological Association. Not for further distribution.

APA Handbook of

Psychopathology volume 1 Psychopathology: Understanding, Assessing, and Treating Adult Mental Disorders

James N. Butcher, Editor-in-Chief Jill M. Hooley, Associate Editor

Copyright © 2018 by the American Psychological Association. All rights reserved. Except as permitted under the United States Copyright Act of 1976, no part of this publication may be reproduced or distributed in any form or by any means, including, but not limited to, the process of scanning and digitization, or stored in a database or retrieval system, without the prior written permission of the publisher. Chapter 4 was coauthored by employees of the United States government as part of official duty and is considered to be in the public domain. The opinions and statements published are the responsibility of the authors, and such opinions and statements do not necessarily represent the policies of the American Psychological Association.

Copyright American Psychological Association. Not for further distribution.

Published by American Psychological Association 750 First Street, NE Washington, DC 20002 www.apa.org APA Order Department P.O. Box 92984 Washington, DC 20090-2984 Phone: (800) 374-2721; Direct: (202) 336-5510 Fax: (202) 336-5502; TDD/TTY: (202) 336-6123 Online: http://www.apa.org/pubs/books E-mail: [email protected] In the U.K., Europe, Africa, and the Middle East, copies may be ordered from Eurospan Group c/o Turpin Distribution Pegasus Drive Stratton Business Park Biggleswade Bedfordshire SG18 8TQ United Kingdom Phone: +44 (0) 1767 604972 Fax: +44 (0) 1767 601640 Online: https://www.eurospanbookstore.com/apa E-mail: [email protected] American Psychological Association Staff Jasper Simons, Executive Publisher Brenda Carter, Publisher, APA Books Katherine Lenz, Reference Project Editor, APA Books Typeset in Berkeley by Cenveo Publisher Services, Columbia, MD Printer: Sheridan Books, Chelsea, MI Cover Designer: Naylor Design, Washington, DC Library of Congress Cataloging-in-Publication Data Names: Butcher, James Neal, 1933– editor. | American Psychological Association. Title: APA handbook of psychopathology / James N. Butcher, editor-in-chief. Other titles: Handbook of psychopathology | APA handbooks in psychology. Description: Washington, DC : American Psychological Association, [2018] |    Series: APA handbooks in psychology series | Includes bibliographical references and indexes. Identifiers: LCCN 2017033373| ISBN 9781433828362 | ISBN 1433828367 Subjects: | MESH: Mental Disorders—pathology | Psychopathology Classification: LCC RC467 | NLM WM 140 | DDC 616.89—dc23 LC record available at https://lccn.loc.gov/2017033373 British Library Cataloguing-in-Publication Data A CIP record is available from the British Library. Printed in the United States of America First Edition http://dx.doi.org/10.1037/0000064-000 10 9 8 7 6 5 4 3 2 1

Copyright American Psychological Association. Not for further distribution.

Contents

Volume 1: Psychopathology: Understanding, Assessing, and Treating Adult Mental Disorders Editorial Board ����������������������������������������������������������������������������������������������������������������������� xi About the Editor-in-Chief�����������������������������������������������������������������������������������������������������xiii Contributors�������������������������������������������������������������������������������������������������������������������������� xv A Note From the Publisher��������������������������������������������������������������������������������������������������� xix Introduction ������������������������������������������������������������������������������������������������������������������������� xxi Part I. Issues in Understanding Adult Psychopathology����������������������������������������������������� 1 Chapter 1. Introduction to Understanding Psychopathology�������������������������������������������������� 3 James N. Butcher and Jill M. Hooley Chapter 2. History of Developments in Understanding Abnormal Behavior ������������������������ 13 German E. Berrios and Ivana S. Marková Chapter 3. Diagnosis and Classification of Psychopathology������������������������������������������������ 41 Thomas A. Widiger and Cristina Crego Chapter 4. Examination of Neurological and Neuropsychological Features in Psychopathology�������������������������������������������������������������������������������������������������� 65 Colleen E. Jackson and William P. Milberg Chapter 5. Behavioral Genetic Insights on the Development of Psychopathology���������������� 91 Matt McGue, Gretchen Saunders, and Irving I. Gottesman Chapter 6. Sociocultural Factors in Psychopathology �������������������������������������������������������� 127 Fanny M. Cheung and Winnie W. S. Mak Chapter 7. Understanding Psychopathology in Immigrant Populations ���������������������������� 149 Giselle Hass Part II. The Role of Assessment in Psychopathology������������������������������������������������������� 167 Chapter 8. Evaluating Psychopathology With Personality Assessment Instruments���������� 169 Robert E. Erard, David S. Nichols, and Alan Friedman Chapter 9. Neuropsychological Assessment������������������������������������������������������������������������ 201 Carlton Gass

vii

Contents

Chapter 10. Understanding Functional Magnetic Resonance Imaging�������������������������������� 221 Zachary P. Infantolino, Jessica I. Lake, and Gregory A. Miller Chapter 11. Assessing Psychopathology in High-Risk Occupations������������������������������������ 245 James N. Butcher, Chris M. Front, and Deniz S. Ones Chapter 12. Assessment of Psychopathology in Older Adults �������������������������������������������� 273 Julie A. Lutz, Jarred V. Gallegos, and Barry A. Edelstein Chapter 13. Integrating Clinical Information and Developing Effective Reports���������������� 301 Marvin W. Acklin Part III. Clinical Manifestations of Psychopathology ����������������������������������������������������� 319

Copyright American Psychological Association. Not for further distribution.

Chapter 14. Neurocognitive Disorders�������������������������������������������������������������������������������� 321 Maya Yutsis, Allyson C. Rosen, and Gayle K. Deutsch Chapter 15. Schizotypy, Schizotypic Psychopathology, and Schizophrenia: Understanding the Nature, Basis, and Manifestation of the Schizophrenia Spectrum���������������������������������������������������������������������������������� 343 Mark F. Lenzenweger Chapter 16. Stress and Its Sequelae: Depression, Suicide, Inflammation, and Physical Illness������������������������������������������������������������������������������������������ 375 George M. Slavich and Randy P. Auerbach Chapter 17. Mood Disorders������������������������������������������������������������������������������������������������ 403 Diego A. Pizzagalli, Alexis E. Whitton, and Christian A. Webb Chapter 18. Anxiety Disorders�������������������������������������������������������������������������������������������� 429 Thomas L. Rodebaugh, Jaclyn S. Weisman, and Natasha A. Tonge Chapter 19. Obsessive-Compulsive and Related Disorders ������������������������������������������������ 455 David F. Tolin and Kristen S. Springer Chapter 20. Substance-Related and Addictive Disorders ���������������������������������������������������� 481 Shosuke Suzuki and Hedy Kober Chapter 21. Eating Disorders ���������������������������������������������������������������������������������������������� 507 Pamela K. Keel Chapter 22. Somatic Symptom and Related Disorders�������������������������������������������������������� 531 Michael Witthöft, Maria Gropalis, and Florian Weck Chapter 23. Personality Disorders: Current Scientific Status and Ongoing Controversies �������������������������������������������������������������������������������������������������� 557 Scott O. Lilienfeld and Robert D. Latzman Part IV. Treatment Considerations in Psychopathology������������������������������������������������� 607 Chapter 24. Psychopathology and Risk of Suicide�������������������������������������������������������������� 609 Brianna J. Turner, Evan M. Kleiman, and Matthew K. Nock Chapter 25. Incorporation of Therapeutic Assessment Into Treatment With Clients in Mental Health Programming������������������������������������������������������������ 631 Filippo Aschieri, Francesca Fantini, and Stephen Edward Finn Chapter 26. Treatment of Psychopathology in Survivors of Torture ���������������������������������� 643 Solvig Ekblad, James M. Jaranson, and Marianne C. Kastrup

viii

Contents

Chapter 27. Cognitive–Behavioral Couples-Based Interventions for Relationship Distress and Psychopathology�������������������������������������������������������������������������� 661 Melanie S. Fischer and Donald H. Baucom Chapter 28. Families and Mental Disorders������������������������������������������������������������������������ 687 Jill M. Hooley and David J. Miklowitz Chapter 29. Effectiveness of Psychotherapy������������������������������������������������������������������������ 705 Kim de Jong and Robert J. DeRubeis

Copyright American Psychological Association. Not for further distribution.

Part V. Ethical and Legal Issues in Psychopathology ����������������������������������������������������� 727 Chapter 30. Ethical Clinical Practice: Negotiating a Whole Lot of Gray in a Wise Way ���� 729 Janet L. Sonne and Jennifer L. Weniger Chapter 31. Forensic Mental Health Practice���������������������������������������������������������������������� 751 Harold J. Bursztajn and Stanley L. Brodsky Index������������������������������������������������������������������������������������������������������������������������������������ 767

ix

Copyright American Psychological Association. Not for further distribution.

Copyright American Psychological Association. Not for further distribution.

Editorial Board

EDITOR-IN-CHIEF James N. Butcher, PhD, Professor Emeritus, Department of Psychology, University of Minnesota, Minneapolis ASSOCIATE EDITORS Volume 1 Jill M. Hooley, DPhil, Professor of Psychology, Department of Psychology, Harvard University, Cambridge, MA Volume 2 Philip C. Kendall, PhD, Distinguished University Professor and Laura H. Carnell Professor of Psychology, Department of Psychology, Temple University, Philadelphia, PA

xi

Copyright American Psychological Association. Not for further distribution.

Copyright American Psychological Association. Not for further distribution.

About the Editor-in-Chief

James N. Butcher, PhD, is professor emeritus in the Department of Psychology at the University of Minnesota. He was awarded honorary doctorates for his international personality assessment research (Doctor Honoris Causa) from the Free University of Brussels, Brussels, Belgium, in 1990 and from the University of Florence, Florence, Italy (Laurea ad Honorem in Psychology) in 2005. He is a fellow of the Society for Personality Assessment and received the Bruno Klopfer Award from the Society for Personality Assessment in 2004 for longstanding contributions to personality assessment. He has maintained an active research program in the areas of abnormal psychology, personality assessment, cross-cultural personality factors, and computer-based personality assessment. He has conducted extensive research on the Minnesota Multiphasic Personality Inventory (MMPI) in a broad range of contexts. Dr. Butcher was born in West Virginia. He enlisted in the U.S. Army when he was 17 years old and served in the airborne infantry for 3 years, including a 1-year tour in Korea during the Korean War. After military service, he attended Guilford College, graduating in 1960 with a BA in psychology. He received his MA in experimental psychology in 1962 and a PhD in clinical psychology from the University of North Carolina at Chapel Hill. He was first associate director and then director of the clinical psychology program at the University of Minnesota for 19 years. He was a member of the University of Minnesota Press’s MMPI Consultative Committee, which undertook the revision of the MMPI in 1989. He is a former editor of Psychological Assessment, a journal of the American Psychological Association, and he serves as consulting editor or reviewer for numerous other journals in psychology and psychiatry. During his career, Dr. Butcher was actively involved in developing and organizing disaster response programs for dealing with human problems after airline disasters. He organized a model crisis intervention disaster response for the Minneapolis–St. Paul Airport and organized and supervised the psychological services offered after two major airline disasters: Northwest Flight 255 in Detroit, Michigan, and Aloha Airlines on Maui, Hawaii. Dr. Butcher has published 64 books and more than 250 articles in the fields of abnormal psychology, cross-cultural psychology, and personality assessment. His publications in psychology include basic research works in abnormal psychology, personality assessment, and the MMPI, including research methodology and computer applications of psychological tests. Dr. Butcher’s recent publications include Using the MMPI–2 in Forensic Assessment, Abnormal Psychology (17th ed.), A Beginner’s Guide to the MMPI–2, and the Oxford Handbook of Personality Assessment, as well as a memoir, Korea: Traces of a Forgotten War.

xiii

Copyright American Psychological Association. Not for further distribution.

Copyright American Psychological Association. Not for further distribution.

Contributors

Marvin W. Acklin, PhD, Department of Psychiatry, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu Filippo Aschieri, PhD, European Center for Therapeutic Assessment, Catholic University of the Sacred Heart, Milan, Italy Randy P. Auerbach, PhD, Department of Psychiatry, Harvard Medical School, Boston, MA; McLean Hospital, Belmont, MA Donald H. Baucom, PhD, Department of Psychology and Neuroscience, University of North Carolina–Chapel Hill German E. Berrios, DPhil, Department of Psychiatry, University of Cambridge, Cambridge, England Stanley L. Brodsky, PhD, Department of Psychology, University of Alabama, Tuscaloosa Harold J. Bursztajn, MD, Department of Psychiatry, Harvard Medical School, Boston, MA James N. Butcher, PhD, Department of Psychology, University of Minnesota, Minneapolis Fanny M. Cheung, PhD, Department of Psychology, Chinese University of Hong Kong, Hong Kong, China Cristina Crego, Doctoral Candidate, Department of Psychology, University of Kentucky, Lexington Kim de Jong, PhD, Institute of Psychology, Leiden University, Leiden, the Netherlands Robert J. DeRubeis, PhD, Department of Psychology, University of Pennsylvania, Philadelphia Gayle K. Deutsch, PhD, ABPP-CN, Department of Neurology and Neurosciences, Stanford Health Care, Stanford, CA Barry A. Edelstein, PhD, Department of Psychology, West Virginia University, Morgantown Solvig Ekblad, PhD, Academic Primary Healthcare Centre, and Cultural Medicine Research Group, Department of Learning, Informatics, Management and Ethics, Karolinska Institutet, Stockholm, Sweden Robert E. Erard, PhD* Francesca Fantini, PhD, European Center for Therapeutic Assessment, Catholic University of the Sacred Heart, Milan, Italy Stephen Edward Finn, PhD, Center for Therapeutic Assessment, Austin, TX Melanie S. Fischer, PhD, Department of Psychology and Neuroscience, University of North Carolina–Chapel Hill Alan Friedman, PhD, Department of Psychiatry and Behavioral Sciences, Northwestern University, Chicago, IL Chris M. Front, PsyD, Office of Aerospace Medicine, Federal Aviation Administration, Washington, DC xv

Contributors

Copyright American Psychological Association. Not for further distribution.

Jarred V. Gallegos, MA, Department of Psychology, West Virginia University, Morgantown Carlton Gass, PhD, ABN, ABPP-CP, ABAP, Neuroscience Center, Tallahassee Memorial Healthcare, Tallahassee, FL Irving I. Gottesman, PhD* Maria Gropalis, PhD, Department of Psychology, Johannes Gutenberg–University Mainz, Mainz, Germany Giselle Hass, PsyD, ABAP, independent practice, Washington, DC Jill M. Hooley, DPhil, Department of Psychology, Harvard University, Cambridge, MA Zachary P. Infantolino, PhD, Department of Psychology, Stony Brook University, Stony Brook, NY Colleen E. Jackson, PhD, ABPP-CN, Department of Psychology, VA Boston Healthcare System, and Department of Psychiatry, Boston University School of Medicine, Boston, MA James M. Jaranson, MD, MA, MPH, Department of Psychiatry, University of Minnesota, Minneapolis Marianne C. Kastrup, MD, PhD, independent practice, Copenhagen, Denmark Pamela K. Keel, PhD, Department of Psychology, Florida State University, Tallahassee Evan M. Kleiman, PhD, Department of Psychology, Harvard University, Cambridge, MA Hedy Kober, PhD, Departments of Psychiatry and Psychology, Yale University, New Haven, CT Jessica I. Lake, PhD, Department of Psychology, University of California, Los Angeles Robert D. Latzman, PhD, Department of Psychology, Georgia State University, Atlanta Mark F. Lenzenweger, PhD, Department of Psychology, State University of New York at Binghamton Scott O. Lilienfeld, PhD, Department of Psychology, Emory University, Atlanta, GA; Melbourne School of Psychological Sciences, University of Melbourne, Melbourne, Australia Julie A. Lutz, MS, Department of Psychology, West Virginia University, Morgantown Winnie W. S. Mak, PhD, Department of Psychology, Chinese University of Hong Kong, Hong Kong, China Ivana S. Marková, MD, Center for Health and Population Sciences, Hull York Medical School, University of Hull, Hull, England Matt McGue, PhD, Department of Psychology, University of Minnesota, Minneapolis David J. Miklowitz, PhD, Department of Psychiatry and Behavioral Sciences, University of California, Los Angeles William P. Milberg, PhD, Department of Psychology, Harvard Medical School, and VA Boston Healthcare System, Boston, MA Gregory A. Miller, PhD, Department of Psychology and Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles David S. Nichols, PhD, retired, Portland, OR Matthew K. Nock, PhD, Department of Psychology, Harvard University, Cambridge, MA Deniz S. Ones, PhD, Department of Psychology, University of Minnesota, Minneapolis Diego A. Pizzagalli, PhD, Department of Psychiatry, Harvard Medical School, Boston, MA; McLean Hospital, Belmont, MA Thomas L. Rodebaugh, PhD, Department of Psychological and Brain Sciences, Washington University, St. Louis, MO Allyson C. Rosen, PhD, ABPP-CN, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, and VA Palo Alto Health Care System, Palo Alto, CA

xvi

Copyright American Psychological Association. Not for further distribution.

Contributors

Gretchen Saunders, Doctoral Candidate, Department of Psychology, University of Minnesota, Minneapolis George M. Slavich, PhD, Department of Psychiatry and Biobehavioral Sciences, University of California, and Cousins Center for Psychoneuroimmunology, University of California, Los Angeles Janet L. Sonne, PhD, Loma Linda University Behavioral Medicine Center, and School of Behavioral Health, Department of Psychology, Loma Linda University, Redlands, CA Kristen S. Springer, PhD, Institute of Living, Hartford, CT Shosuke Suzuki, BS, Department of Psychiatry, Yale University, New Haven, CT David F. Tolin, PhD, Institute of Living, Hartford, CT; Department of Psychiatry, Yale School of Medicine, New Haven, CT Natasha A. Tonge, Doctoral Candidate, Department of Psychological and Brain Sciences, Washington University, St. Louis, MO Brianna J. Turner, PhD, Department of Psychology, University of Victoria, Victoria, British Columbia, Canada Christian A. Webb, PhD, Department of Psychiatry, Harvard Medical School, Boston, MA; McLean Hospital, Belmont, MA Florian Weck, PhD, Department of Psychology, University of Potsdam, Potsdam, Germany Jaclyn S. Weisman, Doctoral Candidate, Department of Psychological and Brain Sciences, Washington University, St. Louis, MO Jennifer L. Weniger, PhD, School of Behavioral Health, Loma Linda University, Loma Linda, CA Alexis E. Whitton, PhD, Department of Psychiatry, Harvard Medical School, Boston, MA; McLean Hospital, Belmont, MA Thomas A. Widiger, PhD, Department of Psychology, University of Kentucky, Lexington Michael Witthöft, PhD, Department of Psychology, Johannes Gutenberg–University Mainz, Mainz, Germany Maya Yutsis, PhD, ABPP-CN, Department of Neurology and Neurosciences, Stanford Health Care, Stanford, CA * deceased

xvii

Copyright American Psychological Association. Not for further distribution.

Copyright American Psychological Association. Not for further distribution.

A Note From the Publisher

The APA Handbook of Psychopathology is the 27th publication to be released in the American Psychological Association’s APA Handbooks in Psychology® series, instituted in 2010. The series comprises both single volumes and multivolume sets focused on core subfields or on highly focused content areas and emerging subfields. A complete listing of the series titles to date can be found on pp. ii–iii. Each publication in the series is primarily formulated to address the reference interests and needs of researchers, clinicians, and practitioners in psychology. Each also addresses the needs of graduate students for well-organized and highly detailed supplementary texts, whether to “fill in” their own specialty areas or to acquire solid familiarity with other specialties and emerging trends across the breadth of psychology. Many of the sets additionally bear strong interest for professionals in pertinent complementary fields (i.e., depending on content area), be they corporate executives and human resources personnel; psychiatrists; doctors, nurses, and other health personnel; teachers and school administrators; counselors; legal professionals; and so forth. Under the direction of small and select editorial boards consisting of top scholars in the field, with chapters authored by both senior and rising researchers and practitioners, each reference commits to a steady focus on best science and best practice. Coverage converges on what is currently known in the particular topical area (including basic historical reviews) and the identification of the most pertinent sources of information in both the core and evolving literature. Volumes and chapters alike pinpoint practical issues; probe unresolved and controversial topics; and highlight future theoretical, research, and practice trends. The editors provide guidance to the “dialogue” among chapters through internal crossreferencing that demonstrates a robust integration of topics. Readers are thus offered a clear understanding of the complex interrelationships within each field. With the imprimatur of the largest scientific and professional organization representing psychology in the United States and the largest association of psychologists in the world, and with content edited and authored by some of its most respected members, the APA Handbooks in Psychology series is an indispensable and authoritative reference resource for researchers, instructors, practitioners, and field leaders alike.

xix

Copyright American Psychological Association. Not for further distribution.

Copyright American Psychological Association. Not for further distribution.

Introduction

The study of psychopathology has a long and interesting history going back to ancient times. Over the years, much has been accomplished in explaining and understanding mental health problems, but the extent of research on and the theoretical exploration of mental illness requires considerable attention and effort to remain current. There is an important need to evaluate new developments and to integrate new information into the known and accepted facts from past contributions. How does the APA Handbook of Psychopathology address the broad and extensive research and theoretical basis of the mental health problems that are found in contemporary psychology and incorporate new information into present thinking? Although many of the ideas underlying psychopathology described in this handbook have their roots in writings of ancient civilizations, the conceptualizations and professional activities involved in this field are constantly changing. Change is a big part of life, and new research or novel theories that arise today can have an impact on the ways in which mental health professionals and researchers view problems in the future. A comprehensive and up-to-date handbook on the field of psychopathology requires a broad range of experts who have extensively studied and communicated their observations to others in an effective manner. New and current research-based viewpoints on psychological disorders are vital resources for the development of the field. One important goal of this handbook project was to bring together, in a comprehensive but unified resource, the current viewpoints of a broad range of distinguished scholars in the mental health field who have made substantial contributions to understanding psychopathology. We wanted to provide a contemporary perspective on the wide range of research and theoretical approaches to understanding, prevention, and management of mental health problems that people experience. Moreover, we wanted to provide the reader with a resource for understanding the numerous ways in which professionals and organizations deal with the problems resulting from psychopathology. This handbook was conceived with the goal of providing a state-of-the-art review of the field in order to provide effective coverage of the scope and issues therein. This handbook is divided into two separate, although obviously interconnected, volumes. Volume 1 focuses on adult psychopathology; Volume 2, on child and adolescent psychopathology. The topics chosen by the editorial team represent the most current and relevant research areas and are key factors in understanding the field of psychopathology today.

xxi

Introduction

Copyright American Psychological Association. Not for further distribution.

Our approach to understanding mental disorders involves much more than a description or categorization of the behavioral symptoms of specific disorders as defined in existing diagnostic manuals. In addition to contemporary definitions of mental disorders, we include a number of topics that provide a comprehensive perspective on psychopathology—how disorders are caused, prevented, assessed, studied, and dealt with—to enable a better understanding of them. We have attempted to provide in-depth coverage of the major diagnostic problem areas and extensive subfields in psychopathology today. Given the current expanding diagnostic areas in psychopathology manuals and resources, however, we could not include all areas of psychopathology being studied in contemporary psychology, psychiatry, forensic mental health, school psychology, and other areas in which mental health problems may be addressed. In this handbook, we focus on the most prominent and widely researched diagnostic areas in psychopathology. This handbook was developed to provide a broad perspective on new scientific developments in areas such as genetics, cognitive problems, brain imaging, behavioral observation, personality assessment, and classification, as well as changes in social and government policy and legal decisions. The handbook also addresses the issue of how these diverse areas of study can considerably influence the knowledge base and stimulate new treatments for people who experience mental disorders. The rapid progress of the field, however, presents considerable challenges. As some chapters illustrate, changing or evolving ideas are sometimes viewed with skepticism or are difficult to integrate into existing viewpoints. As the diagnostic systems defining mental disorders evolve over time and developers attempt to incorporate new research and theoretical developments into them, changes can alter diagnostic categorization in dramatic ways. For example, the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (American Psychiatric Association, 2013) eliminated entire diagnostic classification components based on previous diagnostic perspectives—such as the fourth edition’s axial system of classification—that were widely used in clinical decision making, even though they are still relied on by some institutions and practitioners and in assessment procedures. In selecting chapter topics for this handbook, we followed a biopsychosocial approach to provide comprehensive coverage of research and developments in the contexts in which behavior abnormalities occur. We have attempted to include broad coverage of many mental disorders and various aspects of professional development. We have provided material on each disorder in a logical and consistent way and focused on its significant aspects: (a) the clinical picture, describing the symptoms of the disorder and its associated features; (b) factors involved in the development of the disorder; (c) relationships or comorbidity with other disorders specific to the conditions addressed; and (d) different treatment approaches. Moreover, we have attempted to examine the biological and psychosocial evidence underlying the disorders. In addition to ensuring that cultural, social, and environmental factors are appropriately addressed, we include specific chapters dealing with the influence of such factors on psychopathology. Each volume of the APA Handbook of Psychopathology was constructed to address the research interests and educational needs of researchers, clinicians, and practitioners in psychology and allied behavioral fields. We also wanted to address the needs of graduate students in psychology who require well-organized, detailed supplementary texts to gain a sound basis of information. In addition, we wanted to address the needs of other established specialties and discuss emerging trends across the breadth of psychology. Many of the chapters will be of strong interest to professionals in related fields, such as physicians, xxii

Copyright American Psychological Association. Not for further distribution.

Introduction

psychiatrists, and other health professionals who encounter mental health problems in their practice. To provide a current and comprehensive picture of psychopathology, we invited an extensive variety of accomplished scholars across broad areas of the field to contribute topics. We considered it particularly important for the handbook to contain wide-ranging international perspectives. Thus, many efforts were made to enlist international contributors to further enhance the handbook’s diversity. Authors or coauthors from a number of countries participated in writing chapters to provide a distinctive perspective on mental health problems in other countries as well as in the United States. By inviting the leading scientists, scholars, and practitioners in the broad field of psychopathology research and practice to contribute to this reference work, we hope that the handbook will not only provide a critical and current review but will also help set the agenda for future research and future directions in practice for the next decade. We also hope that this handbook will help expand and diversify the scope of psychology to be more inclusive and less Western in orientation. The development of this handbook has, for me, been a valuable and enjoyable experience—especially working again with Philip C. Kendall and Jill M. Hooley on a psychopathology project. Jill and Phil have been enormously helpful in gathering this broad range of outstanding contributors in psychology and psychiatry, using our three independent (but overlapping) networks of researchers and practitioners who are highly experienced in the field of psychopathology. Our editorial collaboration has produced a wide-ranging professional approach to understanding psychopathology today. Each of us is an established researcher, an experienced teacher, and a practicing clinician in different areas of psychopathology. Each of us also brings a different perspective on psychopathology research. These different perspectives have come together as a comprehensive collection of viewpoints on the current status of the understanding of mental disorders. The editorial board’s diverse areas of practice and research provide readers with an inclusive perspective on the field of psychopathology. This approach emphasizes the value of basic research and the application of viable practice strategies. We have greatly enjoyed establishing this list of contributors and committing to the important task of providing information in a strong and helpful resource. DISCLOSURE STATEMENTS James N. Butcher served on the Minnesota Multiphasic Personality Inventory—2 (MMPI–2) Restandardization Committee to develop the MMPI–2 and MMPI—Adolescent (MMPI–A). The three members of the original committee, James N. Butcher, W. Grant Dahlstrom, and John R. Graham, chose not receive any royalties from sales of the MMPI–2 and MMPI–A test booklets and manuals, manual supplements, scoring materials, profile sheets, and the like. These authors wrote new items and revised original MMPI items for the MMPI–2 and MMPI–A. They collected the normative sample used in the norm development of the MMPI–2 and MMPI–A and clinical data sets used to validate the revised scales between 1982 and 1989. Butcher cocreated several scales for the MMPI–2, such as the Content Scales; the MMPI–A Content Scales; the Superlative Self-Expression, or S, scale; and the four alcohol and drug problem scales (MMPI–2 Addiction Potential Scale and Addiction Admission Scale, MMPI–A Alcohol/Drug Problem Acknowledgment and Alcohol/Drug Problem Proneness). Butcher was also the cocreator of nine translations of the MMPI or MMPI–2 and does not receive any royalties for those works. Members of the MMPI Restandardization Committee xxiii

Introduction

Copyright American Psychological Association. Not for further distribution.

agreed to forgo any royalties on the new versions of the MMPI resulting from the committee’s work during the Restandardization Project. Butcher does receive royalty payments for some of the books he has published on the MMPI and MMPI–2, although the royalties on some books were donated to the MMPI–2 Symposium and Workshop Series that he directed for 38 years. Butcher receives royalty payments for his development of the Minnesota Reports, a computer-based interpretation system for the MMPI–2 and MMPI–A. He also receives royalties from Pearson Publishing for a textbook on abnormal psychology. Jill M. Hooley receives royalties from Pearson Publishing in connection with textbook sales. She does not receive financial compensation from any pharmacology company, and she is not a member of any speakers panels. Similarly, Philip C. Kendall is not on any speakers bureaus, nor is he employed by or supported by any pharmacology company. He receives royalties from publishers (Guilford Press, Workbook Publishing, several foreign language translations) for the sales of materials related to the treatment of anxiety in youth. He has received financial support (from the National Institute of Mental Health [NIMH], National Institute of Child Health and Human Development [NICHD], and the MacArthur Foundation) for his research projects. ACKNOWLEDGMENTS We would like to acknowledge the support and contributions of all the people who made this series possible. We would like to thank Susan Reynolds of APA Books for her longstanding and pragmatic vision of what published resources are needed in the field of psychology; Ted Baroody, former Reference Director at APA, for his organizational prowess and practical strategies for making chapter drafts into effective professional resources; and Katherine Lenz, Reference Project Editor at APA, for her efforts to bring these ideas into reality in a comprehensive way. The series of handbooks the American Psychological Association has produced in the past several years have contributed substantially to the understanding of important topics in psychology. James N. Butcher would especially like to thank the former Director of APA Books, Julia Frank-McNeil, who invited him to serve as Editor-in-Chief of this handbook. James N. Butcher would also like to thank his wife, Carolyn L. Williams, for her support and advice that made his contribution to this work possible. She provided substantial content and recommended contributors to invite to write a chapter. He would also like to acknowledge his family for their continued support and tolerance of his efforts in projects such as this one. His two daughters, Sherry Butcher Wickstrom and Holly Butcher Grant, and son, Dr. Janus Dale Butcher, are always supportive of his academic pursuits, even though they might interfere at times with their interests in getting together. Jill M. Hooley is grateful to Kip Schur for his love, advice, and support during the development and production of Volume 1. She also thanks her graduate students for their ideas and insights and for their enthusiasm for research in psychopathology. Philip C. Kendall thanks his graduate students and colleagues for their contributions and support. The collaborations make for a pleasant and successful work environment. He also thanks the NIMH (MH063747, MH086438) and the NICHD (HD080097) for support of the research that has advanced the understanding and treatment of psychological disorders in youth. Finally, Phil thanks his spouse, Sue, and his sons, Mark and Reed, who have always been supportive of his academic pursuits.

xxiv

Introduction

APA’s invitation to develop a handbook of psychopathology was a great opportunity to help expand the pathway to understanding and developing further research in the field of psychopathology by bringing a highly distinguished team of researchers together in a single resource. It is hoped that the readers of this handbook will gain as much understanding and perspective on psychopathology from this reference as we have in working with the contributors involved to bring it into existence. James N. Butcher Editor-in-Chief

Reference

Copyright American Psychological Association. Not for further distribution.

American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). Washington, DC: Author.

xxv

Copyright American Psychological Association. Not for further distribution.

Copyright American Psychological Association. Not for further distribution.

Part I

Issues in Understanding Adult Psychopathology

Copyright American Psychological Association. Not for further distribution.

Chapter 1

Introduction to Understanding Psychopathology

Copyright American Psychological Association. Not for further distribution.

James N. Butcher and Jill M. Hooley

There is much more to understanding psychopathology than a mere description of symptoms can provide. Acquiring a full perspective of the meaning and impact of mental disorders requires consideration of underlying causal factors, an understanding of family history and the social context in which the disorder developed, and an exploration of the various cognitive and behavioral aspects of the person’s personality functioning obtained through careful assessment. Information about effective treatment strategies and factors pertinent to management of problem behavior in society is also required. Given the complexity of topics and speed of progress in abnormal psychology, gaining and maintaining a current and detailed perspective on various disorders presents significant challenges to mental health professionals. This is all the more important given the prevalence of psychological distress. The number of people with mental disorders or substance abuse problems is high. Data from the National Institute of Mental Health for 2014 suggest that, in the United States, an estimated 43.6 million adults age 18 years or older (or 18.1% of the population) experienced some form of mental illness in the past year. Within this population, 21.8% were female and 14.1% were male. These figures are no doubt underestimates because they do not include substance use disorders, such as drug- or alcohol-related disorders. The primary goals of this two-volume APA Handbook of Psychopathology are to provide up-to-date information on important topics in adult, child, and adolescent psychopathology along with broad

coverage of core issues in research and applications to mental health issues. The handbook approaches the study of psychopathology from several perspectives to provide the reader with an understanding of the complex and evolving nature of this field. The first volume of the handbook series, Psychopathology: Understanding, Assessing, and Treating Adult Mental Disorders, is devoted to providing a comprehensive overview of different aspects of psychopathology in adult populations. Chapters are organized into five main topic areas: issues in understanding adult psychopathology; the role of assessment in psychopathology; clinical manifestations and descriptions of mental disorders; treatment considerations; and important ethical, legal, and administrative issues. These describe some situations in which psychopathology can affect society at large. Volume 2, Child and Adolescent Psychopathology, includes chapters that address issues in psychopathology among children and adolescents and specifically deals with the mental illnesses that occur in young people. This volume is also divided into five sections to provide the reader with a comprehensive overview of several related fields that focus on the issues in abnormal psychology of children and adolescents (see Volume 2, Chapter 1, for an overview of chapters in that volume). The audience for the handbook includes psychologists teaching and conducting research in abnormal psychology, as well as trainees and graduate students in clinical and counseling psychology. It will also provide a valuable resource for current

http://dx.doi.org/10.1037/0000064-001 APA Handbook of Psychopathology: Vol. 1. Psychopathology: Understanding, Assessing, and Treating Adult Mental Disorders, J. N. Butcher (Editor-in-Chief) Copyright © 2018 by the American Psychological Association. All rights reserved.

APA Handbook of Psychopathology: Psychopathology: Understanding, Assessing, and Treating Adult Mental Disorders, edited by J. N. Butcher and J. M. Hooley Copyright © 2018 American Psychological Association. All rights reserved.

3

Butcher and Hooley

mental health practitioners and professionals from other fields, such as forensic psychology and psychiatry, who want to learn about new developments and maintain a contemporary understanding of psychopathology.

Copyright American Psychological Association. Not for further distribution.

OVERVIEW AND ORGANIZATION The organization and development of the chapters in this handbook were undertaken with the primary goal of providing a comprehensive and current research-based perspective on the field of abnormal psychology. The authors, who were invited to explore critical issues in the professional understanding and management of psychopathology, are noted experts in their fields. They describe the principles and applications pertinent to the mental health issues, highlight research evidence, and consider practical applications involved in the topic. We also sought to include international authors to obtain a broader and more comprehensive perspective. Authors from many countries including Canada, China, Costa Rica, Australia, Denmark, Germany, Italy, the Netherlands, Singapore, Sweden, and the United Kingdom have all participated in writing chapters. In addition, throughout the volumes we highlight issues that are important for anyone interested in psychopathology to appreciate and understand. These issues include ■■ ■■ ■■

■■ ■■

■■

■■ ■■ ■■ ■■

Historical paths to understanding mental illness The complex nature of symptom manifestation Awareness of past mistaken beliefs about mental disorders Causal influences in psychopathology Cultural and environmental factors in the development of mental disorders Diagnostic classification and the evolution of classification process over time Gender differences in psychopathology Prevalence of mental health problems Comorbidity of mental disorders Social impact of mental disorders.

Wherever possible we have included chapters that address and include these issues. A number of specific topics apart from the diagnostic description 4

of mental disorders are also included in this handbook series. In this way, we hope to bring into focus the influence of psychopathology in other professional areas.

Issues in Understanding Adult Psychopathology Chapters in the first section are designed to provide appropriate theoretical perspectives and background knowledge essential to understanding psychopathology. For example, it is important to recognize that interest in psychopathology has a long history. Antique religious stone tablets, currently housed in the British Museum, contain detailed behavioral descriptions of people who possessed characteristics suggestive of antisocial personality disorder. Although these tablets were originally produced in ancient Asurbanipal in Mesopotamia (what is now Iraq) in about 800 BC, they describe behavior that is remarkably similar to that what would be considered to reflect antisocial personality disorder within our current diagnostic classification systems (AbdulHamid & Stein, 2013). Chapter 2, by German E. Berrios and Ivana S. Marková, provides an overview of historical contributions to the understanding of psychopathology. This chapter provides the reader with a historical perspective that highlights the major historical influences that have shaped the field. To study psychopathology, or to treat those who suffer from it, some form of nomenclature is needed. In Chapter 3, Thomas A. Widiger and Cristina Crego provide a contemporary perspective on the diagnostic endeavor. Their chapter clarifies the issues and principles of diagnostic classification. It also illustrates how the evolving classification system both influences and reflects contemporary views. The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM–5; American Psychiatric Association, 2013) has expanded the number of diagnoses but has also altered their conceptualization by eliminating widely used previous diagnostic procedures such as the axial system of fourth edition of the DSM (DSM–IV; American Psychiatric Association, 1994). This chapter highlights the issues emerging with the DSM–5 classification system and its value in research and clinical practice (see American Psychiatric Association, 2013).

Copyright American Psychological Association. Not for further distribution.

Introduction to Understanding Psychopathology

Widiger and Crego also discuss the somewhat different system for categorizing mental health symptoms provided by the National Institute of Mental Health, referred to as the Research Domain Criteria, or RDoC (Etkin & Cuthbert, 2014). The RDoC system offers a matrix for clinical research that departs from the traditional (medical model–based) use of categories derived from clinical observation. (The RDoC system is also discussed in Chapter 10 by Infantolino, Lake, and Miller and in Chapter 23 by Lilienfeld and Latzman.) In Chapter 4, Colleen E. Jackson and William P. Milberg describe the cognitive and mental processes underlying psychopathology, with particular reference to how those processes are disrupted by brain damage. Jackson and Milberg also highlight changes in the organization of neurocognitive disorders now reflected in the DSM–5. This chapter is followed by a consideration of genetic factors in psychopathology. As newer and ever more sophisticated techniques emerge, genetic research is progressing at a rapid pace. In Chapter 5, Matt McGue, Gretchen Saunders, and Irving I. Gottesman describe the theoretical and empirical support for the genetic influence on the manifestation of some mental illnesses. Genetic concepts are explained, and efforts to specify the genetic factors that underlie heritable effects for several different clinical conditions are discussed. This chapter offers readers a basic understanding of the complexity of the human genetic processes, describing candidate gene approaches and genewide association studies. McGue et al. also highlight issues that need to be kept in mind when significant genetic associations are reported in the scientific literature. A very different tradition for studying the development of psychopathology is reflected in the cultural, learning-based approach. People who have been uprooted from their original country of development and find themselves living in a new and highly different environment often experience great personal turmoil. Other factors such as discrimination, prejudice, and barriers to integration can further compound these adjustment problems. Foster (2001) identified several areas in which traumatic experiences can lead to psychological distress; for example, people may have experienced events

before migration that forced them to relocate; experienced negative events during their transit; experienced problems during their asylum seeking and resettlement; or had to live in inadequate living conditions in the host country. It is important to consider the stress of immigration and the nature of the person’s prior adjustment in appraising their current experiences (Butcher, Hass, Greene, & Nelson, 2015; Hass, Dutton, & Orloff, 2000). Chapter 6, by Fanny M. Cheung and Winnie W. S. Mak, focuses on the influence of culture on the development of psychological disorders. They incorporate contemporary research and theoretical views to provide a current cross-cultural perspective. The need to incorporate cross-cultural training in psychology to ensure the cultural relevance of mental health practice is also addressed. This is illustrated further in Chapter 7, in which Giselle Hass considers the mental health problems that frequently occur in people who are recent immigrants to the United States. This chapter also addresses factors that influence how the problems of recent immigrants are understood.

The Role of Assessment in Psychopathology An important field in the understanding of psychopathology is psychological assessment. Several chapters whose authors were invited for this handbook focus on assessment strategies and methodologies for obtaining relevant information for evaluation of individuals with mental health problems and provide an overview of strategies and methods for assessing psychopathology through personality assessment instruments. In Chapter 8, Robert E. Erard, David S. Nichols, and Alan Friedman provide a substantial overview of the major and most widely used assessment techniques for understanding psychopathology. In particular, the value of the Minnesota Multiphasic Personality Inventory in providing a perspective on mental health symptoms is illustrated. In Chapter 9, Carlton Gass describes the basic issues and strategies in neuropsychological assessment and provides the core principles and applications for understanding psychopathological problems in brain damage or illness. This chapter gives a perspective on current effectiveness of methods and includes discussion 5

Copyright American Psychological Association. Not for further distribution.

Butcher and Hooley

of potential future directions for the field. Readers seeking to be informed about the newest techniques in brain imaging will also find Chapter 10 exceedingly valuable. In this chapter, Zachary P. Infantolino, Jessica I. Lake, and Gregory A. Miller provide a thoughtful and detailed overview of procedures currently in use to study brain processes. Another important contribution of this chapter is that the authors describe what commonly used techniques such as functional magnetic resonance imaging can (and cannot) tell one. They also highlight new directions for future research in this area and consider the implications of these approaches for treatment. Personality disorders or mental health problems among employees in the workplace can have a powerful negative impact on the public. This is especially true of employees in certain occupations. For example, people who are employed as airline pilots who become suicidal, police officers who use excessive force, or air traffic controllers who do not maintain vigilance in directing air traffic can adversely affect the lives of others (see Butcher, 2002; Detrick, 2012; Kay, Thurston, & Front, 2013). This highlights the importance of assessing potential problems in preemployment evaluations. In Chapter 11, James N. Butcher, Chris M. Front, and Deniz S. Ones discuss the influence of psychopathology on safety in the workplace, with a particular focus on high-risk occupations. In another area of broad contemporary concern, Julie A. Lutz, Jarred V. Gallegos, and Barry A. Edelstein, in Chapter 12, describe the assessment strategies used for understanding psychopathology in older adults. The final chapter in the psychological assessment section involves the integration of clinical information and developing effective reports. In Chapter 13, Marvin W. Acklin considers the topic of communication of assessment results to accurately and effectively report conclusions regarding the manifestation of a client’s psychopathology. Cautions and limitations of the communication strategies are also noted.

Clinical Manifestations of Psychopathology Chapters in this section provide the reader with information about some of the most important and most prevalent forms of psychopathology. Factual 6

research-based information is extremely important in any scientific field, but particularly so in the area of abnormal psychology, wherein myths and mistaken beliefs can prove harmful. In developing this handbook, we asked authors to (a) define disorders and related variants, being mindful of dimensional issues; (b) provide incidence and prevalence information, including a consideration of comorbidity; (c) include information describing how the diagnoses are identified and specified; (d) describe factors such as age and gender distributions; (e) discuss specific factors pertinent to the treatments that are effective in modifying the patient’s behavior; (f) incorporate important past research defining the clinical problem areas; and (g) include, where appropriate, potential future directions for research and development. The chapters included in this handbook meet these goals well and are substantial resources for understanding psychopathology. Maya Yutsis, Allyson C. Rosen, and Gayle K. Deutsch provide current information about neurocognitive disorders in Chapter 14. Considered here are disorders that were formerly (in the DSM–IV) referred to as dementia, delirium, amnestic, and other cognitive disorders. The authors include a discussion of the value of the new DSM–5 classification compared with previous approaches. Another disorder that is characterized by neurocognitive impairment is schizophrenia. Indeed, when the German psychiatrist Emil Kraepelin first gave a name to this severe form of mental illness in 1896, he called it dementia praecox. Kraepelin’s use of this term was meant to signify that the disorder was characterized by a premature (early-onset) form of mental decline. Kraepelin was correct on both counts, although the diagnostic term schizophrenia that is used today comes from Eugen Bleuler, a Swiss psychiatrist who was a contemporary of Kraepelin’s. It is also noteworthy that, in his monograph on the topic, Bleuler used the subtitle “The Groups of Schizophrenias” making it clear that, in his opinion, this disorder was not a single diagnostic entity (see Hooley, Butcher, Nock, & Mineka, 2017). It is therefore perhaps appropriate that, in a contemporary consideration of this topic, Mark F. Lenzenweger, in Chapter 15, focuses on schizotypy,

Copyright American Psychological Association. Not for further distribution.

Introduction to Understanding Psychopathology

schizotypic psychopathology, and schizophrenia. In this chapter, the reader is introduced to the concept of the schizophrenia spectrum and the variants of psychopathology that are thought to be reflective of an underlying vulnerability to schizophrenia, broadly defined. As such, Lenzenweger’s chapter provides a thoughtful and considered discussion of clinical conditions that extend beyond the narrow conceptualization of schizophrenia found in the DSM–5. In Chapter 16, George M. Slavich and Randy P. Auerbach consider the important topic of stress. Stress has long been an important topic in psychopathology. People with schizophrenia are highly sensitive to stress (Howes, McCutcheon, Owen, & Murray, 2017). Stress is also directly implicated in disorders such as posttraumatic stress disorder (PTSD; see Bryant, 2015; Cohen & Mannarino, 2016). Many decades ago, seminal work by Brown and Harris (1978) first drew attention to the link between life events and depression. Measuring stress, however, has created many challenges. In their highly informative chapter, Slavich and Auerbach describe self-report and interview-based approaches to life stress measurement. They also provide recommendations for how, and over what period, stress should be measured in future research studies. The chapter also considers the biological consequences of stress. By providing a current and highly informative review of immune system processes that are activated by stress, Slavich and Auerbach increase readers’ understanding of how stress may have broad and profound effects on both physical and mental health. One of the most prevalent forms of psychopathology is depression. Mood disorders are comprehensively described and discussed in Chapter 17 by Diego A. Pizzagalli, Alexis E. Whitton, and Christian A. Webb. In their chapter, the authors provide an excellent overview and description of major depression and bipolar disorder, highlighting how these diagnoses are identified and specified as well as describing how the prevalence of mood disorders is influenced by such factors as age, ethnicity, and gender. The chapter also includes a thoughtful review of biological and social and environmental factors implicated in depression, along with

valuable information on a wide range of treatment approaches. In the DSM–5, several changes were made to the disorders included in the anxiety disorders section. In Chapter 18, Thomas L. Rodebaugh, Jaclyn S. Weisman, and Natasha A. Tonge begin by raising the thought-provoking question of what, exactly, anxiety disorders are. They then provide up-to-date information on the incidence and prevalence of anxiety disorders defined in DSM–5, seeing this grouping as reflecting more of an approach of convenience rather than as a statement about the legitimacy of the current classification system. This, again, reflects the critical thinking approach that is characteristic of the handbook chapters. David F. Tolin and Kristen S. Springer, in Chapter 19, consider disorders included in the new category of obsessive-compulsive and related disorders, providing current information not only on obsessive-compulsive disorder but also on hoarding disorder, body dysmorphic disorder, and trichotillomania. This is a daunting task. However, their chapter is highly accessible and provides a wealth of information on the nature and treatment of a broad range of clinical conditions. In Chapter 20, Shosuke Suzuki and Hedy Kober provide an overview and description of ­substance-related and addictive disorders, which are common clinical conditions. A Substance Abuse and Mental Health Services Administration survey found that in 2014 approximately 21.5 ­million people ages 12 years or older had a substance use disorder in the past year, including 17.0 million people with an alcohol use ­disorder, 7.1 million with an illicit drug use ­disorder, and 2.6 million who had both an alcohol use and an illicit drug use disorder. These estimates have been similar over the past 6 years (Center for Behavioral Health Statistics and Quality, 2015). Suzuki and Kober describe how these diagnoses are identified and specified and note the relevant social factors that influence them, such as age, ethnicity, and gender. Specific factors pertinent to treatment are also addressed. Many changes to eating disorder diagnoses were included in the DSM–5. For example, binge eating disorder is now included as an official diagnosis, having been considered only as a provisional 7

Copyright American Psychological Association. Not for further distribution.

Butcher and Hooley

condition in need of further study in the DSM–IV. In Chapter 21, Pamela K. Keel provides a comprehensive and research-based summary of anorexia nervosa, bulimia nervosa, and binge eating disorder. As Keel notes, one of the greatest misconceptions about eating disorders is that they are volitional and represent a choice on the part of the afflicted individual. Her chapter provides key details about the clinical presentation and prevalence of the most common and worrisome forms of eating disorders. Sociocultural, psychological, and biological risk factors are also considered, and treatment approaches are well described. We are far from a full understanding of the causes of eating disorders. Keel’s chapter provides a valuable resource for readers seeking a contemporary perspective on this complex topic. In Chapter 22, Michael Witthöft, Maria Gropalis, and Florian Weck consider the new diagnostic category of somatic symptom and related disorders. This grouping contains clinical conditions that, in DSM–IV, were termed somatoform disorders. ­Witthöft et al. explain the changes that were made in DSM–5 and provide a thoughtful and thorough summary of how the diagnoses recognized in DSM–5 are identified and treated. Chapter 22 also reflects current thinking concerning how transient physical symptoms such as pain or fatigue can develop into somatic symptom disorders. The third section ends with a consideration of personality disorders. Many of the clinical conditions that are discussed in this handbook are frequently comorbid with personality pathology. The complex and often controversial topic of personality disorders is well described in Chapter 23 by Scott O. Lilienfeld and Robert D. Latzman. Essentially, these authors have provided us with two chapters. In the first part of Chapter 23, Lilienfeld and Latzman explore and delineate the complexity of personality disorders, outlining the history of this field and highlighting long-standing controversies. They describe how the field got to where it is today and raise many concerns about decisions that were made along the way. Having discussed personality and the notion of personality disorders as well as the various ways in which these can be conceptualized, Lilienfield and Latzman, in the second part of the chapter, describe what is currently known about the 8

personality disorders that are recognized in DSM–5. They consider the various specific disorders in turn, describing their key features and providing information on incidence and prevalence. Comorbidity, which is a major concern in the current classification system, is also described. Whenever possible, specific factors pertinent to the treatment or management of personality problems are also noted. The result is a highly informative chapter that addresses the central conceptual and methodological concerns that plague this area and yet also provides a synthesis of what is known about the currently recognized and familiar DSM categories.

Treatment Considerations in Psychopathology Several chapters that focus on treatment-related topics are included in this section. These chapters are designed to provide the reader with a broad perspective on treatment or treatment-relevant issues. Authors were invited to provide ideas and insights that might give the reader a greater understanding of problems or strategies needed to effectively manage or treat individuals with psychological disorders. Some of the chapters focus on special conditions that require careful attention in therapy (e.g., people at high risk for suicide) or treatment issues that can arise when working with special populations (such as victims of torture). Other chapters provide overviews of treatment approaches that can be used with distinct groups (e.g., couples) or that highlight the importance of family dynamics in the recovery process. The fourth section of the volume begins with a focus on suicidal behavior. Suicide ranks among the top 10 causes of death in Western countries. In Chapter 24, Brianna J. Turner, Evan M. Kleiman, and Matthew K. Nock discuss the link between psychopathology and suicidal behavior, exploring some of the terminology that is important in understanding this topic. The chapter provides an up-to-date review of the sociodemographic, psychological, and biological factors that are associated with elevated risk for suicide. Best practices with regard to assessing suicide risk are also described, and interventions designed to reduce suicidal ideation and suicide attempts are included. Other chapters in this section address more specific treatment topics. In Chapter 25, Filippo

Copyright American Psychological Association. Not for further distribution.

Introduction to Understanding Psychopathology

Aschieri, Francesca Fantini, and Stephen Edward Finn provide an overview of how providing psychometric test feedback to a client and incorporating information about the client’s psychological assessment can be a key variable in the treatment process. This approach can also be used to help therapists navigate roadblocks or impasses that may develop in the course of therapy by providing new insights and targets for intervention. The empirical research support for this treatment approach is described, and examples of how the process works are included to provide further illustration. A troubling topic is discussed in Chapter 26; Solvig Ekblad, James M. Jaranson, and Marianne C. Kastrup provide an overview of the mental health and physical problems resulting from torture. The chapter provides an understanding of how various torture techniques can be used to damage victims and describes the prevalence of mental health problems that can result from torture. The authors also include a discussion of how DSM–5 currently deals with the impact of torture and consider differences and similarities between torture-related problems and PTSD. It is important to remember that clinical disorders do not occur in a social vacuum. Moreover, disorders such as depression are closely intertwined with relationship distress, with each predicting the later development of the other (Whisman & Bruce, 1999; Whisman & Uebelacker, 2009). Wellmeaning partners can also engage in behaviors that inadvertently maintain or exacerbate a psychological disorder such as might happen when a partner accommodates the symptoms of obsessive disorder. In Chapter 27, Melanie S. Fischer and Donald H. Baucom describe couples-based interventions that can be used in the treatment of mental health problems. In addition to incorporating illustrative examples, these authors provide valuable clinical guidelines and recommendations for implementing couples-based approaches. They also offer suggestions for how partners can be included when individual treatment is the primary form of intervention. In Chapter 28, Jill M. Hooley and David J. Miklowitz provide an overview and description of the role of the family environment in major mental illness. The family factors that are associated with poorer clinical

outcomes for patients with disorders such as schizophrenia, bipolar disorder, and major depression are described. There is also a focus on understanding how and why negative family environments develop in the context of coping with mental illness in a relative. In addition, information about effective approaches and strategies that can be used for family-based interventions is presented. Chapter 29, the final chapter in this section, provides a thoughtful review of the effectiveness of psychotherapy in the treatment of psychological disorders. Kim de Jong and Robert J. DeRubeis consider the evidence supporting cognitive–behavioral therapy, psychodynamic and psychoanalytic therapy, and humanistic and experiential psychotherapies in the treatment of depression, anxiety, and personality disorders. They also consider how treatment effects should be estimated and highlight issues that should be a focus of attention in future comparative outcome research. The result is an informative and accessible chapter that provides a wealth of valuable information about the current status of psychotherapy research.

Ethical and Legal Issues in Psychopathology The final section of this handbook presents two chapters on topics that are of general importance with regard to professional practice. Mental health professionals have a responsibility to act in an ethical manner, respecting the trust and expectations of help that patients place in them (American Psychological Association, 2017; Kitchener & Kitchener, 2012). Yet clinical practice routinely brings with it situations that pose complex ethical challenges. In Chapter 30, Janet L. Sonne and Jennifer L. Weniger describe the current codes of ethical conduct. They also note how ambiguous many situations are with respect to these guidelines. Sonne and Weniger then offer a new decision-making model that outlines steps that can be worked through to resolve specific ethical issues that may arise. This chapter also underscores the importance of the development of a professional ethical identity for all mental health professionals and trainees. Another special topic of practical concern involves issues related to psychopathology and the 9

Copyright American Psychological Association. Not for further distribution.

Butcher and Hooley

law. Mental disorders are often related to or are causal factors in court cases (Brodsky & Gutheil, 2016; Butcher et al., 2015; Goldstein & Bursztajn, 2011). Chapter 31, by Harold J. Bursztajn and Stanley L. Brodsky, addresses a growing area in psychopathology today—courtroom testimony about clients’ mental health status. Factors associated with effective testimony about a client’s mental health status in a legal context are described. This chapter also includes discussion of the most prominent issues with regard to court-related mental health testimony. Taken together, the chapters in this volume provide readers with comprehensive information about a wide range of topics in adult psychopathology. The authors have worked hard to produce timely, thoughtful, and thought-provoking chapters. We hope readers of the handbook will learn much from the material presented here and incorporate this knowledge into their professional lives as researchers, clinicians, and mental health professionals.

References Abdul-Hamid, W. K., & Stein, G. (2013). The Surpu: Exorcism of antisocial personality disorder in ancient Mesopotamia. Mental Health, Religion, and Culture, 16, 671–85. http://dx.doi.org/10.1080/13674676. 2012.713337 American Psychiatric Association. (1994). Diagnostic and statistical manual of mental disorders (4th ed.). Washington, DC: Author. American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). Washington, DC: Author. American Psychological Association. (2017). Ethical principles of psychologists and code of conduct (2002, Amended June 1, 2010 and January 1, 2017). Retrieved from http://www.apa.org/ethics/code/ index.aspx Brodsky, S. L., & Gutheil, T. G. (2016). The expert witness: More maxims and guidelines for testifying in court (2nd ed.). http://dx.doi.org/10.1037/14732-000 Brown, G. W., & Harris, T. O. (1978). Social origins of depression: A study of psychiatric disorder in women. New York, NY: Free Press. Bryant, R. A. (2015). Early intervention after trauma. In U. Schnyder & M. Cloitre (Eds.), Evidence based treatments for trauma-related psychological disorders: A practical guide for clinicians (pp. 125–142). http:// dx.doi.org/10.1007/978-3-319-07109-1_7 10

Butcher, J. N. (2002). Assessing pilots with “the wrong stuff”: A call for research on emotional health factors in commercial aviators. International Journal of Selection and Assessment, 10, 1–17. Butcher, J. N., Hass, G. A., Greene, R. L., & Nelson, L. D. (2015). Using the MMPI–2 in forensic assessment. http://dx.doi.org/10.1037/14571-000 Center for Behavioral Health Statistics and Quality. (2015). Behavioral health trends in the United States: Results from the 2014 National Survey on Drug Use and Health. Rockville, MD: Substance Abuse and Mental Health Services Administration. Retrieved from https://www.samhsa.gov/data/sites/default/files/ NSDUH-FRR1-2014/NSDUH-FRR1-2014.pdf Cohen, J. A., & Mannarino, A. P. (2016). Posttraumatic stress disorder and persistent complex bereavement disorder. In M. K. Dulcan (Ed.), Dulcan’s textbook of child and adolescent psychiatry (2nd ed., pp. 345–364). http://dx.doi.org/10.1176/ appi.books.9781615370306.md16 Detrick, P. (2012). Police officer preemployment evaluations: Seeking consistency if not standardization? Professional Psychology: Research and Practice, 43, 162. http://dx.doi.org/10.1037/ a0026874 Etkin, A., & Cuthbert, B. (2014). Beyond the DSM: Development of a transdiagnostic psychiatric neuroscience course. Academic Psychiatry, 38, 145–150. http://dx.doi.org/10.1007/s40596-013-0032-4 Foster, R. P. (2001). When immigration is trauma: Guidelines for the individual and family clinician. American Journal of Orthopsychiatry, 71, 153–170. http://dx.doi.org/10.1037/0002-9432.71.2.153 Goldstein, A. M., & Bursztajn, H. J. (2011). Capital litigation: Special considerations. In E. Y. Drogin, F. M. Dattilio, R. L. Sadoff, & T. G. Gutheil (Eds.), Handbook of forensic assessment: Psychological and psychiatric perspectives (pp. 145–170). http:// dx.doi.org/10.1002/9781118093399.ch7 Hass, G. A., Dutton, M. A., & Orloff, L. E. (2000). Lifetime prevalence of domestic violence against Latina immigrants: Legal and policy implications. International Review of Victimology, 7, 93–113. http:// dx.doi.org/10.1177/026975800000700306 Hooley, J. M., Butcher, J. N., Nock, M., & Mineka, S. (2017). Abnormal psychology (17th ed.). Boston, MA: Pearson. Howes, O. D., McCutcheon, R., Owen, M. J., & Murray, R. M. (2017). The role of genes, stress, and dopamine in the development of schizophrenia. Biological Psychiatry, 81, 9–20. http://dx.doi.org/10.1016/ j.biopsych.2016.07.014 Kay, G. G., Thurston, A. J., & Front, C. M. (2013). Commercial airline pilot and air traffic controller

Introduction to Understanding Psychopathology

selection. In C. H. Kennedy & G. G. Kay (Eds.), Aeromedical psychology (pp. 37-62). Aldershot, England: Ashgate.

Whisman, M. A., & Uebelacker, L. A. (2009). Prospective associations between marital discord and depressive symptoms in middle-aged and older adults. Psychology and Aging, 24, 184–189. http:// dx.doi.org/10.1037/a0014759

Copyright American Psychological Association. Not for further distribution.

Kitchener, R. F., & Kitchener, K. S. (2012). Ethical foundations of psychology. In S. J. Knapp, M. C. Gottlieb, M. M. Handelsman, & L. D. VandeCreek (Eds.), APA handbook of ethics in psychology: Vol. 1. Moral foundations and common themes (pp. 3–42). Washington, DC: American Psychological Association.

Whisman, M. A., & Bruce, M. L. (1999). Marital dissatisfaction and incidence of major depressive episode in a community sample. Journal of Abnormal Psychology, 108, 674–678. http:// dx.doi.org/10.1037/0021-843X.108.4.674

11

Chapter 2

History of Developments in Understanding Abnormal Behavior

Copyright American Psychological Association. Not for further distribution.

German E. Berrios and Ivana S. Marková

Two types of explanation are available in Western cultures: diachronic (longitudinal, historical) and synchronic (cross-sectional, structural). According to the conventional view, the synchronic approach is adequate to explain nomothetic objects, that is, those studied by the natural sciences (Naturwissenschaften), and the diachronic approach is superior to understand idiographic objects, that is, those studied by the human, cultural, or social sciences (Geisteswissenschaften). Although many scholars are guided by this binary view, others feel that it overemphasizes the distinction between natural and social sciences (Schurz, 2014). However, earlier efforts to create a unified view of the sciences were abandoned because in choosing the natural sciences as the epistemological paragon (McGuinness, 1987), they managed to wipe out what is central to the social sciences, that is, their capacity to deal with meaning, individuality, and subjectivity. In this chapter, we take the view that, to be of any use to the understanding of human suffering, psychiatry, psychology, and psychopathology must be reconceptualized as hybrid disciplines, that is, as deep conceptual combinations of natural and social sciences. This reconceptualization dictates that the construction of these three disciplines be studied diachronically. The task of this chapter, therefore, must be the contextualized and hermeneutic analysis of the events, protagonists, and conjunctures that have so far partaken in the construction and

activities of the language of psychopathology. The choice of such historical objects has been made on the basis of the analysis of mainly German, French, Italian, and British primary sources. This chapter summarizes work undertaken and published by the authors in the past forty years (Berrios, 1996). Be that as it may, there is not space in this chapter to include accounts of madness before the 17th century. This cut-off has been chosen with care. Accounts before the scientific revolution are hard to understand, for current terms central to our narrative such as mind and body (as determined by post-Cartesian ontology and epistemology) have no equivalent counterpart in the pre-Cartesian world. It is, in fact, very difficult to conceive of or imagine what referent the ancients had in mind for terms such as spirit, soul, psyche, and body. For example, one ought to be careful to call Hippocrates a modern physician on account of his claim that epilepsy was not a sacred but a natural disease. This cannot be done because in Hippocrates’s mind, what was natural (i.e., what pertains to fy9 sις) evoked a notion combining the celestial and the terrestrial that one cannot even begin to understand. In other words, Hippocrates explained nature and body differently; they did not mean the same thing to him as they do to us. The issue is that he drew the boundaries of these concepts in a very different place, and hence they are incommensurate with what Descartes was to draw later.

http://dx.doi.org/10.1037/0000064-002 APA Handbook of Psychopathology: Vol. 1. Psychopathology: Understanding, Assessing, and Treating Adult Mental Disorders, J. N. Butcher (Editor-in-Chief) 13 Copyright © 2018 by the American Psychological Association. All rights reserved.

APA Handbook of Psychopathology: Psychopathology: Understanding, Assessing, and Treating Adult Mental Disorders, edited by J. N. Butcher and J. M. Hooley Copyright © 2018 American Psychological Association. All rights reserved.

Berrios and Marková

HISTORIOGRAPHICAL PREAMBLE

Copyright American Psychological Association. Not for further distribution.

Abnormal Behavior Since the 15th century, the English term behavior has been used to refer to both the intentional and the moral aspects of action. For example, describing the relationship between Ariadne and Thaeseus, Caxton (1490/1890) wrote, “She hadde pyte of hym / and for hys honneste behauoure [emphasis added]/ Began to be taken with his loue” (p. 118). Later usages iterate this dual meaning. Thus, Hobbes (1651/1996) wrote, “By manners, I mean not here, decency of behaviour; as how one man should salute another, or how a man should wash his mouth, or pick his teeth before company, and such other points of the small morals” (Part I, Chap. 11, p. 69). In regard to the origin of the term, Hobbes’s contemporaries wrote, “Behave. . . . I rather think that it may have come from the French Behavan. To contain oneself, or keep within bounds; i.e. to be mannerly” (Anonymous, 1691). In due course, the double meaning of behavior caused a translational problem. Renderable in French as conduite or comportement, in 1908 Piéron chose the latter (Laugier, 2004). Revived at the beginning of the 20th century by behaviorism, a bowdlerized form of the concept of behavior was used to conjure away the need to deal with subjectivity. Although this usage had a measure of success within psychology, it did not work in psychiatry, where introspective acts remained necessary for the definition and capture of mental symptoms. To deal with this issue, McDougall (1912) felt forced to broaden the meaning of behavior and to add the adjective abnormal.1 Thus born, the meaning of abnormal behavior started to depend on the rather obscure definitions of behavior and of norm.2 Naming a physical or geometrical “ruler,” the term norm (norma) can already be found in 17thcentury English dictionaries (Holy-Oke, 1659).

Thus, norm meant “rule” and normal that which “is exact, according to rule or square” (Coles, 1677); anormal (the earlier version of abnormal) was in turn defined as “qui n’est pas normal, qui est contre les règles” (Larousse, 1866, p. 417). An ethical dimension was only added to norm during the late 19th century by the neo-Kantians of the Baden School (Kelsen, 1949; Windelband, 1907, pp. 278–317). Deviations from the norm were first called anormal, with the term abnormal developing only later. Since the 17th century, anatomical deviations from the norm have been called anomalies or monstrosities (Duplay, 1870, pp. 221–222). Abnormalities of function were only recognized after the discipline of physiology (based on the conceptual separation of organ and function) was constructed during the 19th century. Also during this period, the debate started about what differentiated the normal from the abnormal. Accounts for the nature of the deviation have since depended on the philosophies in vogue. Before the concept of probability came into play, deviations were considered to be qualitative. Thus, abnormality became a quantitative deviation in medicine only during the early 19th century. From a conceptual viewpoint, quantitative accounts of abnormality are easier to handle because they are defined as gradations along the same putative dimension. Qualitative accounts of abnormality are less so, because they are based on the existence of parallel ontological states. In this sense, becoming abnormal would mean to migrate from one qualitative state to another and hence from one system of norms to another. This raises important issues in regard to the mechanisms involved in the migration, to the definition of the diseased state, and to the understanding of what therapy means. One of the few writers who has accepted the option of a qualitative change is Canguilhem (1978), who has defined the pathologique as a distinct form

Abnormal psychology was concerned with “minds in definitely morbid or pathological states, and those concerned with distinctly unusual or abnormal states of mind which cannot fairly be classed as morbid. The former group consists of two sub-departments: the study of mental diseases proper and that of the psycho-neuroses. The separation of these studies is largely conventional and professional rather than scientific, and there is manifest at the present time a strong tendency to abolish it” (McDougall, 1912, p. 194).

1

Additions needed to deal with the vagueness of abnormal behavior have converted its current definition into a semantic potpourri: “behavior that is atypical or statistically uncommon within a particular culture or that is maladaptive or detrimental to an individual. Such behavior is often regarded as evidence of a mental or emotional disturbance, ranging from minor adjustment problems to severe mental disorder” (VandenBos, 2013, p. 2). In this definition abnormal is clearly parasitical upon concepts such as culture and norm and on a specification of whether the putative deviation is quantitative or qualitative.

2

14

History of Developments in Understanding Abnormal Behavior

Copyright American Psychological Association. Not for further distribution.

of being, as an ontologically different state ruled by its own norms and independent from the state of normality. He wrote, Without being absurd, the pathological state can be called normal to the extent that it expresses a relationship to life’s normativity. But without being absurd this normal could not be termed identical to the normal physiological state because we are dealing with other norms. The abnormal is not such because of the absence of normality. There is no life whatsoever without norms of life, and the morbid state is always a certain mode of living. . . . Man is healthy insofar as he is normative relative to the fluctuations of his environment. . . . The pathological state, on the other hand, expresses the reduction of the norms of life tolerated by the living being, the precariousness of the normal established by disease. (Canguilhem, 1978, p. 228) Of importance to psychiatry, madness, according to this view, becomes a state that is above and beyond the current concept of abnormal behavior.

Understanding and Explanation The English term understanding has been in use since the 12th century to refer to a cognitive power of the mind similar to intelligence (Thouard, 2004). By the end of the 19th century, Dilthey (1977) redefined it as an epistemological act whereby the subjectivity and uniqueness of human actions, as studied by history and the social sciences, could be captured. In Dilthey’s definition, Verstehen included the act of empathy (Apel, 2001) and was chosen as the specific method of research for the human sciences (Martin, 2000). In this sense, it was considered a polar opposite to explanation, the method of choice for understanding in the natural sciences. However, explanation was used until the late 18th century as a metaphorical extension of the original

Latin term for unfolding, uncoiling, removing folds, making flat, and so forth. Early in the next century, the term started to refer to the act of identifying causes by linking objects to laws of nature.3 Like society, nature was believed to be regulated by laws (Armstrong, 1983). Explanations (explanans) therefrom took the form of deductions or syllogisms in which the law of nature appeared as the covering premise and the object to be explained (explanandum) appeared as a minor premise (Glennan, 2006). In spite of the important debate that has taken place since on the concept of explanation (Ruben, 1990), the above structure has changed little. For example, in psychiatry Explanandum E has the following form: Patient P has disease D because general brain function F has been disrupted by a change C. This in spite of the fact that in regard to madness, evidence for the existence of C consists of a proxy marker M, and the relationship between C and D is based on incomplete correlational data. Now, given that, as conventional logical empiricism states, prediction is just the reverse of explanation (Barrett & Stanford, 2006), it is to be expected that psychiatry should be able to reverse E and identify undiagnosed cases of D in the community. The fact that this is not happening is explained by the fact that not enough is yet known about intermediate variables interfering with the effect of E rather than by calling into question the usefulness of the model itself. Whether explanation or understanding is the most appropriate method to capture madness needs exploration. First paired up by Droysen (1936/1977), these epistemological approaches have since overlapped (Feest, 2010). However, they can be differentiated in terms of their object of knowledge, subjective concomitances, and the nature of the relationship between subject and object that each approach entails. Explanation is considered the method of choice in the natural sciences because it explains objects in general rather than each in particular. Understanding is seen as the favorite method in the social sciences because it takes into account the individuality and uniqueness of each

“An individual fact is said to be explained, by pointing out its cause, that is, by stating the law or laws of causation, of which its production is an instance. Thus, a conflagration is explained, when it is proved to have arisen from a spark falling into the midst of a heap of combustibles. And in a similar manner, a law or uniformity in nature is said to be explained, when another law or laws are pointed out, of which that law itself is but a case, and from which it could be deduced” (Mill, 1843, Book III, Chap. 12, p. 1).

3

15

Berrios and Marková

object to be explained. Likewise, a subject accepting an explanation for natural object A, B, or C is said to experience a cognitive change alone, whereas a subject understanding the behavior of person A, B, or C experiences an emotional (empathetic) and aesthetic change. It would seem that understanding means something different from explanation.

ETIOLOGICAL ACCOUNTS: CAUSES AND REASONS Copyright American Psychological Association. Not for further distribution.

Causes The meaning of cause has changed over the centuries.4 According to the Aristotelian view, it named an ontological relationship: Cause was that without which another thing (called effect) could not be. There were four types—material, formal, efficient, and final–and each refers to an aspect of the relationship: We call a cause: (1) that from which (as immanent material) a thing comes into being, e.g. the bronze of the statue and the silver of the saucer, and the classes which include these; (2) The form or pattern, i.e. the formula of the essence, and the classes which include this (e.g. the ratio 2:1 and numbers in general are causes of the octave) and the parts of the formula; (3) That from which the change or the freedom from change first begins, e.g. the man who has deliberated is a cause, and the father a cause of the child, and in general the maker a cause of the thing made and the change-producing of the change; and (4) The end, i.e. that for the sake of which a thing is. e.g. health is the cause of walking. For why does one walk? We say “in order that one may be healthy”, and in speaking thus we think we have given the cause. The same is true of all the means that intervene before the

end, when something else has put the process in motion (as e.g. thinning or purging or drugs or instruments intervene before health is reached); for all these are for the sake of the end, though they differ from one another in that some are instruments and others are actions. (Aristotle, 1984, p. 1600) In regard to the theme of this chapter, it ought to be asked which of the four senses of Aristotelian causation was in the mind of physicians who in earlier periods claimed that mental illness was caused by X? For example, if it was claimed that madness was caused by bad spirits or demons, which of the Aristotelian types was being invoked? The anachronistic view would choose sense (3); that is, it would be claimed that earlier physicians believed that there were real objects called demons acting as efficient causes from the outside to cause madness. However, if (2) (formal cause) was chosen, then their views would seem less extravagant, because their claim would mean that the demons in question were notions connatural and internal to the individual concerned. By the late Renaissance, a debate had ensued as to whether these types were different or of equal importance, or whether they always acted in combination. By the time of the scientific revolution (Dijksterhius, 1961), efficient cause had become the most important (Ott, 2009), and by the 19th century, final causes had mostly been abandoned (Brochin, 1887; Koons, 2000). The current view of causality in medicine (etiology; Riese, 1950) emphasizes internal mechanisms and efficient causes, classified as near and remote (Moulin, 2004).

Reasons Although in common parlance, it is accepted that reasons do provide adequate accounts for human behavior, philosophers argued about whether they can be considered as causal (Anscombe, 1957;

The Latin causa (a translation of the Greek word αιτι′α, or aitía) was primarily a judicial and moral term because it related to responsibility and blame. By metaphorical derivation, the term was later used to explain changes in the natural world (Glare, 1968, pp. 289–290). In classical Greek, αιτι′α also meant both “blame, accusation and charge” (Liddell & Scott, 1996, pp. 44–45) and the act of inquiring why something had occurred. The derivative word αι′τιολογι′α (etiology; searching and providing the cause of a thing), already present in Democritus of Abdera, was transliterated into Latin as aetiologia.

4

16

Copyright American Psychological Association. Not for further distribution.

History of Developments in Understanding Abnormal Behavior

Davidson, 2001; Tanney, 2013). Part of the problem concerns the ambiguity of the word reason (Cassin, 2004). Cicero used the Latin word ratio to translate two (of the three) meanings of the Greek term λογος: “count” and “think” (the third meaning, “discourse,” was translated as dicere). This means that in later European vernaculars, reason tended to refer to the illative (inferential) rather than to the discursive (creative, imaginative) aspects of the intellect. Throughout history human beings have offered reasons for their actions. To say that one did B because of R remains an acceptable way to account for one’s behavior as long as (a) there is a cultural or semantic frame connecting R to B and (b) there is no reason to believe that one is dissembling. Now, can madness also be explained in terms of reasons, or should a neuroscientific narrative be offered instead? This seems important, because the history of madness includes many accounts based on reasons rather than on brain dysfunctions. Should those accounts be included? It has been claimed that some readjustments are required before reasons can be accepted as causes. One relates to whether reasons (as it is mostly believed in medicine, jurisprudence, and moral theory) must be accompanied by intentionality and full awareness. This constraint may be considered as excessive by the epistemology of psychoanalysis: For example, according to this view, it would be sensible to claim that “John gives so many presents to Mary because he is in love with her although he is not aware of it.” In general, it would seem as though research on whether reasons can sometimes be considered as efficient causes of mental disorder must be undertaken, and criteria developed in psychiatry to differentiate between these disorders and those caused by neurobiological change. ETIOLOGICAL ACCOUNTS OF MENTAL AFFLICTIONS SINCE THE 17TH CENTURY

17th Century Hobbes.  As an expression of his “rejection of Antiquity” (Herbert, 1989, p. 10), Thomas

Hobbes (1588–1679) challenged the Aristotelian mode of explanation. He believed that efficient and material causes could not “produce any effect but by being joined together” (Hobbes, 1989, p. 77).5 He redefined essence as a combination of Aristotelian form and finality. By redefining formal cause as “meaning” and final cause as “function,” Hobbes (1989) ­embedded essence into the object itself: For when it is said the essence of a thing is the cause thereof, as to be rational is the cause of man, it is not intelligible; for it is all one, as if it were said, to be a man is the cause of man; which is not well said. And yet the knowledge of the essence of anything, is the cause of the knowledge of the thing itself; for, if I first know that a thing is rational, I know from thence, that the same is a man; but this is no other than an efficient cause. (p. 80) In this sense, knowing the essence of madness meant also knowing how it was caused. It was a perturbation of reason caused by emotions or passions that resulted from “motions of the blood and animal spirits as they variously expand and contract; the causes of these motions are phantasms concerning good and evil excited in the mind by objects” (Hobbes, 1642/1991, p. 54). Hobbes (1651/1996) wrote, To have stronger and more vehement Passions for anything, than is ordinarily seen in others, is that which men call Madnesse. . . . In summe, all Passions that produce strange and unusuall behaviour, are called by the generall name of Madnesse. But of the severall kinds of Madnesse, he that would take the paines, might enrowle a legion. And if the Excesses be madnesse, there is no doubt but the Passions themselves, when they tend to Evill, are degrees of the same. (Chap. 8, p. 54)

“The writers of metaphysics reckon up two other causes besides the efficient and material, namely the essence, which some call formal cause, and the end, or final cause; both of which are nevertheless efficient causes” (Hobbes, 1989, p. 77).

5

17

Berrios and Marková

Copyright American Psychological Association. Not for further distribution.

However, excited or crazy behavior may not always be apparent: “Though the effect of folly, in them that are possessed of an opinion of being inspired, be not visible alwayes in one man, by any very extravagant action, that proceedeth from such passion” (Hobbes, 1651/1996, Chap. 8). Delusions, however, seemed different: If some man in Bedlam should entertaine you with sober discourse; and you desire in taking leave, to know what he were, that you might another time requite his civility; and he should tell you, he were God the father; I think you need expect no extravagant action for argument of his Madnesse. (Hobbes, 1651/1996, Chap. 8, p. 54) In regard to the etiology of madness, Hobbes (1651/1996) contrasted the old with the new: The opinions of the world, both in ­antient and later ages, concerning the cause of madnesse, have been two. Some, deriving them from the Passions; some, from Dæmons, or Spirits, either good, or bad, which they thought might enter into man, possesse him, and move his organs in such strange, and uncouth manner, as mad-men use to do. (Chap. 8, p. 55) Hobbes sided with the former explanation, that is, the view that it was emotions generated by external events that led to a perturbation and true madness (Gert, 1996; Peters, 1967). In summary, madness was a perturbation of reason caused by passions that, in turn, were triggered by external events. Although images of good and evil provided the efficient cause, the perturbed emotions themselves were to be considered the essence of madness, because they both were its internal mechanism and also shaped their expression. Bacon.  Francis Bacon’s (1561–1626) views on causality influenced Thomas Sydenham and

Thomas Willis and through them later medicine and psychiatry: I divide Natural Philosophy into the Inquiry of Causes and the production of effects. The Inquiry of causes I referred to the theoretical part of philosophy. This I subdivide into physics and metaphysics. It follows that the true difference between them must be drawn from the nature of the causes that they inquire into. And therefore to speak plain and go no further about, Physic inquiries and handles the material and efficient causes, and Metaphysics the formal and final. (Bacon, 1905a, p. 459) Bacon believed that Aristotle’s concept of final cause6 was “barren and like a virgin consecrated to God produces nothing” (Bacon, 1905a, p. 473). Bacon (1905b) proposed a definition of formal cause: But when I assign so prominent a part to Forms, I cannot too often warn and admonish men against applying what I say to those forms to which their thoughts and contemplations have hitherto been accustomed. . . . And even in the case of simple creatures I would not be understood to speak of abstract forms and ideas, either not defined in matter at all, or ill defined. For when I speak of Forms, I mean nothing more than those laws and determinations of absolute actuality, which govern and constitute any simple nature as heat, light, weight, in every kind of matter and subject that is susceptible of them. (Book 2, Aphorism 17, p. 321) Bacon is referring here to the internal structure and mechanisms of entities that are responsible for the behavior and presentation of the entity qua entity. He wrote, “The form of a thing is the very thing itself” (Bacon, 1905b, Book 2, Aphorism 18, p. 315). Cranston (1967) has suggested that what Bacon had in mind by his concept of form was what

The notion of final cause underwent a revival during the 19th century because evolutionary theory seemed to suggest that teleological accounts might be needed or possible (Janet, 1900).

6

18

History of Developments in Understanding Abnormal Behavior

Copyright American Psychological Association. Not for further distribution.

Locke later called primary qualities. It is in this sense, however, that forms can be discovered and determined by “true induction.” For example, the formal cause of heat (i.e., its internal mechanism) concerns a motion of “small particles” in bodies. It is not that “heat generates motion or that motion generates heat though both are true in certain cases, but that heat itself, its essence and quiddity, is motion and nothing else” (Bacon, 1905b, Book 2, Aphorism 20, p. 323). Sydenham and Willis.  Although earlier on, Thomas Sydenham (1624–1689; Payne, 1900) is said to have accepted the Hippocratic doctrine of the humors (Dewhurst, 1966, p. 60), his later writings show a Baconian influence on the basis of which he developed an empiricist philosophy of medicine (Yost, 1950). Bacon had suggested that medicine ought to return to the type of observational narrative developed by Hippocrates (Bacon, 1905a, p. 485). Sydenham (1676/1848, p. 148), quoting Bacon approvingly, viewed observation as the right way to read the book of nature, with diseases considered as species of plants (Berrios, 1999b; Picard, 1889). These views led Sydenham to conceive the physician’s role as that of a passive observer rather than an active inquirer into the cause of disease: “So it is with the medical man. His province is to cure diseases, and to do naught else” (Sydenham, 1848, Vol. 2, p. 83). (For Sydenham’s views on madness, see Koutouvidis, Marketos, & Beveridge, 1995). Sydenham favored an internal mechanism model of causality (all diseases had a formal cause; Taylor, 1982). Thomas Willis (1621–1675) is conventionally considered as a sponsor of the “iatro-chemical” theory of disease, the notion that “diseases were perversions of natural fermentations in which the sulphurous and spirituous particles in the sanguinous mass were set in too great a motion, and the blood therefore became overheated” (Frank, 1980, p. 167). Keen on chemistry since his college years, Willis’s first book was on fermentation, which he explained on the basis of chemistry and atomism. Disagreeing, however, with mechanical atomism (which only recognized shape and size as the attributes of final particles), he believed that differentiable identities

could be determined through their chemical composition (Conry, 1982; Vinchon & Vie, 1928). He identified five principles: “spirit, sulphur, salt, water and earth” (Frank, 1980, p. 165). Using his chemical ideas to explain the causes of disease, Willis (1685) complied with the Baconian ideal of internal mechanism: That we may deliver the formal nature and causes of melancholy, we may opine, that the liquor distilled from the blood into the brain (which filling and irrigating all the pores and passages of the brain, and its nervous appendix is both the vehicle and vinculum of the animal spirits) has degenerated from its mild, benign, and subtle nature, into an acetuos and corrosive ­disposition. (p. 462) Locke.  John Locke’s ideas on disease and madness summarize well the 17th-century views of Bacon, Hobbes, and Sydenham. Concerning cause, Locke (1690) wrote, In the notice that our senses take of the constant vicissitude of things, we cannot but observe that several particular, both qualities and substances, begin to exist; and that they receive this their existence from the due application and operation of some other being. From this o­bservation we get our ideas of cause and effect. That which produces any simple or complex idea we denote by the general name, cause, and that which is produced, effect. . . . So that whatever is considered by us to conduce or operate to the producing any particular simple idea, or collection of simple ideas, whether substance or mode, which did not before exist, hath thereby in our minds the relation of a cause, and so is denominated by us. (Book 2, Chap. 26, p. 153) The following well-known statement by Locke (1690) has supported the view that he entertained a view on madness as an intellectual aberration: 19

Copyright American Psychological Association. Not for further distribution.

Berrios and Marková

In fine, the defect in naturals seems to proceed from want of quickness, activity, and motion in the intellectual faculties, whereby they are deprived of reason; whereas madmen, on the other side, seem to suffer by the other extreme. For they do not appear to me to have lost the faculty of reasoning, but having joined together some ideas very wrongly, they mistake them for truths; and they err as men do that argue right from wrong principles. For, by the violence of their imaginations, having taken their fancies for realities, they make right deductions from them. Thus you shall find a distracted man fancying himself a king, with a right inference require suitable attendance, respect, and obedience: others who have thought themselves made of glass, have used the caution necessary to preserve such brittle bodies. (Book 2, Chap. 11, § 13, p. 71) It has been recently argued, however, that disturbances of the passions also play an important role in Locke’s view of madness (Charland, 2014).

18th Century Hume.  To understand David Hume’s contribution, his notion of cause must be explored in relation to three conceptual dichotomies: (a) relations of ideas versus matters of fact, (b) epistemology versus ontology, and (c) conceptual versus psychological analysis. Hume 1. Believed that cause was a matter of fact and not a relation of ideas (like the ideas going into the concept of triangle); 2. Was interested in how one knows about causes (epistemology) rather than in whether causes existed in some realm independent of human beings (ontology); and 3. believed that cause could be explored from a conceptual and a psychological perspective and that each of these approaches led to a different definition of cause (Beebee, 2006).

Hume (1756/2007) offered three criteria to recognize the concept of cause: (a) cause and effect should be contiguous in time and space, (b) cause should occur before effect, and (c) cause and effect (which are different events) must be conjoined: We may define a cause to be an object, followed by another, and where all the objects, similar to the first, are followed by objects similar to the second. Or in other words, where, if the first object had not been, the second never had existed. (p. 56) Subject to the constraints of the Humean analysis, the efficient cause view remained standard during the 18th century. In medical circles, however, the internal mechanism view continued gaining ground, particularly among those who replaced the old chemical explanation with new models of the nervous system (Carlson & Simpson, 1969). Foremost among the latter was the view that brain physiology was based on patterns of vibrations in the nerve (medullary) fibers. Hartley and Battie are good instances of a thinker and physician, respectively, who went on to apply these ideas to the etiology of mental disorder (Hoeldtke, 1967, pp. 47–48). Hartley and Battie.  In his main publication, Observations on Man (Hartley, 1749/1834), David Hartley (1705–1757) made use of associationistic psychology and speculative physiology7 to develop a comprehensive account of human nature that became influential through the work of Joseph Priestley (1733–1804; Warren, 1921, p. 51). Indeed, “Hartley, Priestley, and Darwin in England, and Bonnet in Geneva, made special efforts to update brain physiology in terms of 18th century physics” (Claparède, 1903, p. 15). Hartley (1749/1834) explained mental disorders through an internal mechanism model. In organic delirium, for example, incoherent speech and auditory hallucinations result from the vibrations excited by the distemper in the parts of the brain corresponding to the auditory nerves, or in parts still

“Hartley notion of vibrations . . . was explicitly taken from the Newtonian concepts of motion and ether” (Oberg, 1976, p. 442).

7

20

History of Developments in Understanding Abnormal Behavior

Copyright American Psychological Association. Not for further distribution.

more internal, and consequently the seats of ideas purely intellectual, produce by their associated influence over the organs of speech. . . . That delirious persons have such trains forced upon the eye from internal causes, appears probable. (p. 248) And in Melancholy, he said, “La causa proxima of melancholy is an irritability of the medullary substance of the brain, disposing it upon slight occasions to such vibrations as enter the limits of pain” (Hartley, 1749/1834, p.251). Hartley is using the term la causa proxima as a synonym of Baconian formal cause, that is, what in this chapter is called internal mechanism. William Battie (1703–1776; 1758), the first medical director of St. Luke’s Hospital for Lunaticks in London (founded in 1751), wrote on Humean causality (called by him “remote or external causes”): But, forasmuch as the external objects of sense however forcible their application may be, do not always and in all animal bodies create sight, etc. and moreover, as the very same perceptions do sometimes, at least in disordered subjects, arise without any external object that really affects them; it is impossible but every such external object must be merely accidental, and by no means the sufficient or the necessary cause of such its nervous effect: which sufficient and necessary cause is therefore internal, that is it inhæres in the very frame and ­contribution of the nervous substance itself. (pp. 21–22) After shifting the burden of causality from external causes to internal mechanisms, Battie (1758) resorted to Hartley’s views: Now, as no body whatever can be capable of creating sensation in consequence of its motion and impulse, without pressing upon the nerve affected by such impulse; therefore pressure of the medullary substance contained in the nervous filaments approaches nearer in order to the immediate

cause of sensation, than the motion and impulse of an external object. (p. 25) This illconditioned state of the nerve itself, whereby it is rendered liable to be too much affected with the usual action of such external objects . . . this illconditioned state of the nerve may be inhærent in the internal proper and unknown constitution of the medullary substance. (p. 34) 18th-century classificators.  Nosologists of the Enlightenment, such as Linné, Boissier de Sauvages, Cullen, Sagar, and McBride, held different views on the causes of madness. Linné (1766) defined medicine as the study of the etiology, symptomatology, diagnostic, and prognostic of disease and, following Bacon, differentiated the “essence” of disease (the origin of the symptoms) from its cause (external factors). Mental disorders (order Mentales) resulted from changes in intellect, imagination, and emotions and could be classified, respectively, as Ideales (delirium, paraphrosyne, amentia, mania, daemonia, vesania, and melancholia), Imaginarii (syringmos, phantasma, vertigo, panophobia, and hypochondriasis), and Pathetici (citta, bulimia, polydipsia, satyriasis, erotomania, nostalgia, tarantismus, rabies, hydrophobia, cacositia, antipathia, and anxietas; Linné, 1763). Cullen’s views on cause are consonant with his allegiance to neural pathology, that is, the theory that diseases result from pathological changes in the nervous system. Hence, the neuroses became the largest class in his nosology. These neuroses resulted from changes in sense and movement, which Cullen believed were the two most general functions of the nervous system, and were not accompanied by fever or local lesions: “Sensus et motus laesi, sine pyrexia idiopathica, et sine morbo locali” (Cullen, 1785, p. 182). In addition to the insanities, the neuroses included a large number of medical conditions. After his sojourn in the Americas, Cullen became interested in the effect of climate and external geographic elements on disease. Thus, in regard to external influences his etiological model included a variety of environmental factors. 21

Copyright American Psychological Association. Not for further distribution.

Berrios and Marková

Boissier de Sauvages’s ideas on disease, madness, and their causes were influenced by the views of the Montpellier school of medicine. A friend of Linné’s, with whom he frequently exchanged botanical specimens, Boissier was also a nosologist à la more botanico, that is, he believed that there were ontological similarities between diseases and plants. In contrast with the mechanistic and Cartesian views of the Paris school of medicine, during the 1750s Montpellier medicine defended a vitalistic approach, according to which disease resulted from a disharmony in the body, and hence treatments needed to be personalized and take into account the specific problems of each patient. In the event, and because of the politics of the time, the views of the metropolis became predominant (Williams, 2003). Rather cleverly, Boissier used a combined method: a vitalistic approach for analysis of individual disease and an experimental one for the understanding of disease in general. In this sense he was critical of Thomas Willis’s speculations: However, I am persuaded that it is not possible to establish a sure theory of the animal economy without a knowledge of Physics and Mathematics, and that a man who combines the knowledge of sciences such as Anatomy and Medicine will be in an infinitely better state to practise Medicine successfully. I argue that only the study of Anatomy, experimental Physics and Mathematics can provide a sure theory; and as most of the Physicians ignore these sciences, it is not surprising that Aetiology is full of errors; an erroneous Aetiology is not useful to the Physician, like music to an architect. Aetiology will be unable to direct him in practice, or enhance the study of symptoms, for observation and experience, although most Physicians pretend to the contrary. (Starkstein & Berrios, 2015, p. 485)

19th Century The important epistemological changes that occurred during the 19th century, as a result of the long-term impact of the Enlightenment, are 22

important to the development of new ways of explaining madness. Crucial to these changes was the birth of the social or human sciences as alienists (now called psychiatrists) borrowed freely from both the natural and the social sciences to construct their own discipline. Both efficient causes and internal mechanism were widely discussed in 19th-century psychiatry. However, by the 1850s the latter started to predominate, with authors showing an ever growing interest in the brain events underlying the disease. Nonetheless, efficient causes continued to play a role in the narrative and rhetorical aspects of medical case notes, although by then the section of antecedents was becoming stereotyped and repetitive, with alienists including the same list of life events that at the time were considered crucial to the precipitation of madness. Efficient causes: Hume’s legacy, historicism, and evolutionism.  The fact that alienists continued writing about efficient causes needs explanation. Three reasons for this are briefly discussed: the influence of Hume and somewhat later the impact of historicism and of evolutionary theory. As seen above, Hume’s attack on the epistemological validity of efficient causes had set the logical requirement that cause and effect were different entities and that the former should occur before the latter. This seriatim view governed the work of alienists such as Pinel, Heinroth, Bayle, Prichard, Esquirol, Georget, Feuchtersleben, Morel, and Griesinger, which will be discussed later in this chapter. It was during the 19th century, a historicist period par excellence, when the view was first conceived that time was an essential context for all events (Jacob, 1974), that is, that all things have a natural beginning, development, and end and that progress exists (Gruner, 1981; Lovejoy, 1936/1960). Coined around the middle of the 19th century, Historismus (historicism) is the collective name for ideologies whose common denominator is summarized in Dilthey’s dictum “Was der Mensch sei, erfährt er nur durch der Geschichte” (“what man is, is what he experiences through history”; Dilthey, 2000, p. 162). Vico, Herder, Ranke, Dilthey, Marx, Troeltsch,

Copyright American Psychological Association. Not for further distribution.

History of Developments in Understanding Abnormal Behavior

Croce, Heidegger, Ortega y Gasset, Collingwood, and Mannheim can all be said to have had a historicist approach. Their views are beyond the scope of this chapter. It is, however, only during this century that the dimension of time was gradually incorporated into the notion of madness, eventually leading to the important distinction between acute and chronic disorders and the idea that some types of madness may be related to certain times of life (Berrios, 1996a). Grown thus, during the 19th century, out of an acute awareness of the past, historicism searched both for continuities and for differences and the uniqueness of the past. This approach had two versions. According to anthropological historicism, historicity (Geschichtlichkeit) can only be predicated of human beings. According to cosmological or epistemological historicism, historicity characterizes nature and the cosmos itself. In their reanalysis of efficient causes alienists made use of both types as they searched for repeated triggers of madness in the history of their patients. Evolutionism and historicism were connected. For example, Mannheim (1924) stated that “Evolutionism was the first manifestation of modern historicism” (p. 1). Evolutionism, however, was not a unitary concept (Bowler, 1975). During the 18th century, biological evolution did not imply development in time, and preformationists used the term to mean “unfolding or unrolling of pre-existing parts of the embryo” (Roger, 1993, p. 325). Only during the first half of the 19th century did Lyell (1873) notice that Lamarck had “introduced the element of time into the definition of a species” (p. 436). Nevertheless, it would be historically inaccurate to postulate a neat progression of evolutionary ideas from geology to biology and then to sociology, psychology, and history. In this regard, Green (1962) has stated, “The simultaneous [emphasis added] emergence of evolutionary theories in biology and sociology in the nineteenth century presents an interesting problem in historical interpretation” (p. 419). Although not the first men to suggest that organisms could change (evolve) from generation to generation (Glass, Temkin, & Straus, 1968), Wallace and Darwin were the first to propose a mechanism

for such change (Kottler, 1985). Both Wallace and Darwin called the process whereby random heritable variations occurred in conjunction with competition for survival natural selection. Variations favoring survival were preserved, and their accumulation led to the emergence of new forms highly adapted to their environment. Lamarck (1820/1988) had been willing to accept the idea of species variation even if that meant denying special creation; he believed that such variation revolved around an idealized principle of perfection expressed in the habits and willingness of organisms (Burckhardt, 1977; Jordanova, 1984). Darwin (1874/1883) applied similar principles to the development of the mind and behavior. Writers on efficient causes.  This general emphasis on historical time and longitudinal change supported further the view that efficient causes were a good way of explaining madness, and clinicians spent time compiling lists of antecedents causes. Most tried to combine this type of Humean causality with their growing interest in internal mechanisms. Pinel.  Philippe Pinel’s (1745–1826) views on the etiology of mental illness are modern sounding and susceptible to anachronistic interpretation. He combined three incompatible frames: the Condillacean version of Locke, Cabanis’s ideas on the relationship between brain and behavior,8 and the spiritualism of Maine de Biran (Postel, 1996, p. 195). According to Bercherie (1980), Pinel was happy to accept that the mind depended on the brain and hence mental disorders resulted from brain dysfunction. To explain how diseased organs elsewhere in the body could affect the brain and cause mental disorder, however, Pinel resorted to the old mechanism of sympathy. Sympathy named the “relationship that existed, mediated by the nervous system, between the function of two different bodily organs which were duly separated from each other” (Hecht, 1884, p. 670; Berrios, 2014). The concept of sympathy thus allowed Pinel to muster a long list of putative causes for mental illness that included heredity, blows about the head,

P. J. G. Cabanis (1757–1808), French physician, philosopher, and politician, wrote one of the most influential works on philosophical psychology of the 19th century: On the Relationship Between the Physical and Moral Aspect of Man (Cabanis, 1981; see also Besançon, 1997; Chazaud, 1993; Staum, 1980).

8

23

Berrios and Marková

Copyright American Psychological Association. Not for further distribution.

sadness, and a hard life (Pinel, 1809, pp. 10–54). His etiological views were therefore a combination of traditional efficient causes with a dash of internal mechanisms. Esquirol.  One of the most complete analyses of the causes of madness from the perspective of efficient causes can be found in J. E. Esquirol (1772–1840; 1838): The causes of mental alienation are as numerous, as its forms are varied. They are general or special, physical or moral, primitive or secondary, predisposing or exciting. Not only do climates, seasons, age, sex, temperament, profession and mode of life, have an influence upon the frequency, character, duration, crises, and treatment of insanity; but this malady is still modified by laws, civilization, morals, and the political condition of people. It is, also, produced by causes, whose influence is more immediate, and easily appreciated. (Vol. 1, p. 24) Esquirol (1838) divided efficient causes into physical and moral. Among the former he listed heredity, convulsions of the mother during gestation, epilepsy, menstrual disorders, age, insolation, blows about the head, fevers, syphilis, mercury, intestinal worms, and apoplexy (p. 64), and among the latter were listed domestic trouble, disappointments in love, political events, fanaticism, fear, jealousy, anger, misery, changes in fortune, excessive study, and misanthropy (p. 62). A very similar list can be found in textbooks written by Esquirol’s disciples as well as in many others both in France and elsewhere for the rest of the century. For example, 50 years later, in a large table showing the causes of insanity, and under the headings moral and physical, Tuke (1892, p. 1205) listed pretty much the same efficient causes as had Esquirol in his 1838 textbook. Heinroth.  Psychiatric writings are just a small proportion of the 31 books that J. C. Heinroth (1773–1843) published in his lifetime (Cauwenbergh, 1991). Deeply religious (Mora, 1975), his psychiatric views reflect the ideologies of his time, particularly Hegel’s, and differ from those 24

of his medical contemporaries (who tended to follow Kant or Locke): Any natural phenomenon, anything conditional, is subject to certain conditions and exists through them, and these conditions are known as elements. Our immediate task is to understand the many elements of disturbances of the soul and to define them in all their variety. (Heinroth, 1818/1975, p. 101) In regard to causality, Heinroth (1818/1975) wrote, The word “cause” (unlike the concept “cause”, which was not even known till now), has been used wrongly to denote different moments or condition—for short, the different elements—of ­morbid states; thus as many causes were listed as one found—or believed to have found—elements. Our profound ­German language, which was created for use by philosophers, should dispense with the word “cause” (Ursache: arch object) in all scientific research, for this word is ­self-contradictory. (p. 101) And this is because an object is a thing: and there exists no primary (arch) thing [and hence no primary object] because the primary is that which is unconditional [absolute] (das Unbedingte: the “unthinged”)— the spirit. [It follows from this that no object, including madness, can be primary]. Even less permissible is to speak of causes (in the plural) of a thing or a manifestation, since a thing is produced only by the totality of its conditions; i.e. the thing or nature thereof, is the cause itself. It is only in this relative meaning that the word “cause” (Ursache) has a sense, in that it describes the thing in relation to the totality of its conditions. Thus, a single condition, a single element of a thing, of a manifestation, should

History of Developments in Understanding Abnormal Behavior

Copyright American Psychological Association. Not for further distribution.

not be referred to as cause. (Heinroth, 1818/1975, p. 101) Heinroth, however, only gives the impression of rejecting conventional efficient causes. Instead, he seems to be favoring some form of internal mechanism and is, in fact, following Hegel closely: “A thing is a totality on which converge all determi­ nations of reason and existence . . . such determinations are varied but reflect in the thing itself” (Hegel, 1817/1990, p.73); “substance is cause (Ursache) in as much, on its way to its accidentality, it is reflected upon itself, thus remaining the original thing. . . . Cause is finite and identifies with the effect: rain (cause) causes humidity (effect) but both are one the same thing: water” (Hegel, 1817/1990, pp. 82–83). During the second half of the 19th century, this complex and multidetermined view of causality, in which cause and effect blended into one, became important to internal mechanisms models and later on to psychoanalysis. Bayle.  The 1822 report by A. L. J. Bayle (1799–1858) of six patients combining chronic arachnoiditis and symptomatic phrenitis is considered as the beginning of neuropsychiatry (Coury, 1971; Imbault-Huart, 1981), that is, of the view that all psychiatric disorders have an organic etiology (Postel, 1983). Bayle did not draw this conclusion, although after the death of Antoine Royer-Collard (his mentor) he wrote, “Most of mental disorders are caused by a chronic, primitive inflammation of the brain membranes” (Bayle, 1826, p. xxiv). In 1826, Bayle had as little evidence for this statement as for the more specific claim that the “inflammation started in the membranes and from there spread (secondarily) to the cortex” (p. 401). On account of the myth grown out of his work, Bayle’s views on causality need exploration. He believed that “the chronic meningitis I have described is a primary disease totally different from acute arachnoiditis and of the chronic state of the latter. The term chronic has only been used to emphasize its duration and slow course” (Bayle, 1826, p. 401). Chronic meningitis resulted from “predisposing, occasional, and efficient (or proximal) causes” (pp. 401–402). The former included

gender (male), age (neither too young or too old), temperament (sanguine), profession (military), heredity, sunstroke, blows about the head, alcohol abuse, lifestyle (sedentary), venereal disease, leftsided cardiac hypertrophy, suppression of hemorrhoidal bleeding, history of mental illness, and disappointments and frustrations. Among efficient causes Bayle listed cerebral congestion, which he viewed as a final common pathway. Considering a pathophysiological state as an efficient cause may seem strange to a 21st-century reader, but it is a historical fact that physiology, as the conceptual mediator between anatomy and behavior, had not yet been established during the 1820s. This led Bayle (as Rostan had done before)9 to conceive of congestion as a sort of independent brain state. This redefinition contributed to the development, during the second half of the century, of the internal mechanism notion of causality. Prichard.  J. C. Prichard (1786–1848) wrote on matters anthropological (Stocking, 1973) and psychiatric (Berrios, 1999a). On the latter he wrote, There are many questions connected with the theory of mental disorders, which are yet and will perhaps always remain involved in obscurity; but two departments of inquiry are accessible to us from which we may expect to obtain resources for elucidating the subject. One of these comprehends the antecedents of insanity . . . the other includes necroscopical phenomena. (Prichard, 1835, p. 156) As an etiological account of madness, Prichard (1835) proposed both efficient causes and internal mechanisms: “Care and anxiety, distress, and mental disturbances, are by far the most productive causes of insanity” (p. 182) and it is commonly imagined that madness is much more nearly related to diseases of the abdominal viscera than to those of the thoracic but this opinion is scarcely borne out by necroscopy. . . . vestiges of diseases in the abdominal viscera have

Leon Rostan (1791–1866), French physician and neuropathologist, did important work on the pathophysiology of stroke (Rostan, 1823).

9

25

Berrios and Marková

Copyright American Psychological Association. Not for further distribution.

often been found in the bodies of lunatics. Perhaps the most frequent morbid phenomena discovered in the abdomen, in individuals who have died insane, is the appearance of inflammation in the mucous membrane of the alimentary canal. (pp. 227, 229–230) Feuchtersleben.  A philosopher, physician, and medical educator, Baron Ernst von Feuchtersleben (1806–1849), touched on the etiology of mental disorder in his books on both mental health (Feuchtersleben, 1838/1854) and psychopathology (Feuchtersleben, 1845/1847). In The Dietetics of the Soul, Feuchtersleben (1838/1854) wrote, Under the term “dietetics of the soul” I would comprehend a knowledge of those means by which the soul is preserved in a state of health. . . . my object in the present work is to explain how the spiritual portion of man may be protected from disease. . . . it is enough to know that all disease arises from an internal, or from an external influence. Under the former head are included original germs of disease; for the development of which, however, some external influence is required. Under the latter, are comprehended all external agents which act injuriously on life; yet, here again, we are compelled to admit some original susceptibility arising from weakness. . . . my object [is] to claim for the spirit of man a power whereby he may resist external influences.” (pp. 19, 35) Adopting fully the anatomoclinical model of disease, in his book The Principles of Medical Psychology, Feuchtersleben (1845/1847) wrote, “Since semeiotics10 are nothing more than a reversed etiology, we may spare ourselves all repetition, and from psychical signs infer somewhat somatic causes, and from the somatic somewhat of ­psychical” (p. 193).

Griesinger.  W. Griesinger (1817–1868) was a German physician whose work contributed to the shift in the epistemology of 19th-century alienism from concepts based on Naturphilosophie to a positivist, brain-oriented science (Wahring-Schmidt, 1985). At the time that Griesinger wrote his manual (Griesinger, 1845/1867), causal talk in medicine and psychiatry was coming under the influence of Claude Bernard (1813–1878) who believed that information about causes obtained from the statistical analysis of large groups rarely (if ever) helped with the understanding of individual cases (Brochin, 1887; Déchambre, 1883). Three chapters of Griesinger’s manual are dedicated to etiology: “Causes of Insanity” (a conceptual introduction), “Predisposing Causes” (general and special), and “Modes of Actions of Causes” (psychical, mixed, and organic). Remarkable in detail, these chapters constitute a compendium of psychiatric causality in the middle of the 19th century: Under the head causes in mental as in general pathology are understood all the different classes of circumstance to which may be ascribed an influence on the development of the disease although their mode of connection may be variously exhibited. The causes comprehend, on the one hand, the external circumstances (nationality, climate, season of the year) under the influence of which insanity is generally, with more or less frequency, observed; on the other hand they signify certain external injuries (sunstroke, wounds of the head) of which insanity is frequently a consequence; finally they comprehend certain internal states depending on the organism itself (hereditary predisposition, previous disease, or other general disturbances of the organic mechanisms, such as disease of the lungs, the genital organs, etc.) which we know by experience have an influence in the development of insanity. (Griesinger, 1845/1867, p. 127)

Semiotics is the 19th-century name for the medical discipline that studied the signs and symptoms of disease (also known as semiology). Within alienism (later psychiatry), it started to be called descriptive psychopathology after the 1870s, and during the 20th century some wanted to call it phenomenology (see Berrios, 1996; Landre-Beauvais, 1813).

10

26

History of Developments in Understanding Abnormal Behavior

Copyright American Psychological Association. Not for further distribution.

In other words, Griesinger believed that a complete etiological account of a given mental disorder included a combination of diachronic, antecedent, or efficient causality and knowledge of internal mechanisms. Griesinger (1845/1867) continued, The German psychologists claim the merit of having always understood the etiology and pathogeny of insanity more thoroughly and correctly, and of having more successfully elaborated it, than the French school. Whilst the latter, partly even in recent times (Moreau de Jonnès [sic], Brierre, Parchappe), still adhere to abstract tables of physical and moral causes, in which drunkenness, epilepsy, ambition, prostitution, politics, loss of fortune, &c. are ranged as being of equal importance, the German psychologists (Heinroth and Ideler from the psychic side—Bergman, Flemming, Jacobi, Jessen, Nasse, Zeller, &c. partly with greater regard to bodily causes) have for long insisted on investigating the causes in each individual case; and it has been more the plan with us most carefully to consider all the circumstances, in their various connections, which can influence the development of the morbid state. (pp. 129–130) Concerning the identification of causes at the individual level, the inquiry into the history of the case ought to embrace the whole of the bodily and mental antecedents of the individual. It must commence ab ovo, indeed from former generations—family predisposition—and minutely trace the bodily developments, the habitual state of health, the nature of the diseases to which the patient is subject, and of those which he has already has. (Griesinger, 1845/1867, pp. 128–129) The large amount of data generated by exhaustive case-taking needed to be organized according to

theory, but Griesinger (1845/1867) warned against using the “French way”: We must here endeavour by every means to keep the mind unbiased by this or that theory, and from one-sided preference of one or of certain series of causes; for example, the somatic or the mental. . . . An influence of causation can naturally be attributed with most certainty to those circumstances whose mode of action can be clearly traced, and whose effects therefore may be considered as physiological necessities; or, where this is not the case, to those whose influence is established by reliable statistics. A slight gastric affection, haemorrhoids, or a transient cutaneous eruption, cannot for example, be considered as causes, because no statistics warrant the opinion, no visible connection exists between these affections and insanity either as to their gravity or nature. (pp. 130–131) Morel.  Born in Vienna, B. A. Morel (1809–1873) was a French alienist known to history for coining the term démence précoce (Constant, 1970) and proposing degeneration theory—that is, the view that inherited mental illness could get worse from generation to generation until all reproductive capacity is lost (Friedlander, 1973; Morel, 1857). However, his work on the relationship between the neuroses and the autonomic nervous system, epilepsy, classification, and etiology is probably more important. A Roman Catholic, Morel’s etiological speculations started with a search for a theory that posited a substantial unity between body and mind. This he found in Aquinas: This is notably the theory of St. Thomas according to which the body would confer individuality on the mind (l’âme). Thus, the latter would be incomplete without the former and would have a natural affinity for it. Indeed, without the direct intervention of God the mind alone would even lack in clear ideas. . . . 27

Copyright American Psychological Association. Not for further distribution.

Berrios and Marková

1) essential links without which the substantial unity would not be possible and which underlie normality, and 2) accidental links (in the sense of occasional) which vary according to the individual and are the domain where the will and human liberty operate. Accidental links have an influence on essential ones. (Morel, 1852, pp. 211–212)

idiopathic, sympathetic, and dementia (Morel, 1860, pp. 258–272). In this proposal, Morel (1860) added to the old causal terminology the novelty of lesions (internal mechanisms). Together with Griesinger, he can then be considered a writer who by challenging the value of the probabilistic model of efficient causes prepared the terrain for the acceptance of the internal mechanisms model.

From this, Morel (1852) concluded that “madness develops in the wake of a change in the links between body and mind” and that because of all possible changes, those taking place in the body are the commonest, madness was “a brain disease, idiopathic or sympathetic, that deprives the individual from his physiological and psychological functions, the exercise of his moral freedom, his actions, tendencies and feelings and that affects totally or ­partially his intellectual function” (pp. 214–215). His views hardened later on as he perceived that such causes were based on statistics that were often too superficial to detect interactions between real events:

Internal mechanisms.  Positive and negative factors explain the predominance of internal mechanisms as causal explanations during the second half of the 19th century. The following can be included among the former: an increase in knowledge on the brain (Clarke & Jacyna, 1987; Clarke & O’Malley, 1996), the development (and acceptance) of narratives about the relationship between brain and mind (Engelhardt, 1975), and the predominance, in academic psychiatry, of disease-related concepts over person-related concepts, which started to render madness into an impersonal object of research. Important negative factors were the challenge to probabilistic causality mounted by Claude Bernard, which had the net effect of diminishing the importance of efficient causes as explanations of madness; the unavailability of multivariate statistical models to handle interactions between efficient causes; and the shift experienced by many scientific disciplines from historical to structural accounts (i.e., from diachrony to synchrony). Such change was particularly noticeable in linguistics, where historical (diachronic) accounts of the origin of language were replaced by (synchronic) analyses of the structure of language (Aarsleff, 1982; Droixhe, 1978; Koerner, 1982). These changes did not cause alienists to abandon diachronic causality altogether but drew their attention toward internal mechanisms. This is the case with Meynert, Jackson, Wernicke, and Monakow. In general, academic psychiatrists were keener on internal mechanisms than asylum psychiatrists, which provided another reason for them to feud (Lesky, 1976). In spite of the great technological advances in the neurosciences during the 21st century, there has been little advance in the philosophy of causality in medicine and psychiatry since the changes that occurred

The conventional division of the causes of mental illness between physical and moral (psychological) was no longer adequate to the current needs of science. . . . It may be said that someone’s madness was related to alcohol abuse and hence that it has a physical cause. However, alcohol abuse is a complex phenomenon that may result from habituation or emotional upset or from earlier mental disorder. (Morel, 1860, pp. 77–78) In this case, Morel (1860) argued, it cannot even be decided whether the cause of the person’s current mental illness is physical or moral. After revising both types of causes in the work of other writers, Morel proposed an etiological classification: “Three elements are needed to operate this classification: predisposition, occasional [efficient] cause, and a functional change or lesion [internal mechanism]” (Morel, 1860, p. 250). His classification included six groups of insanities: hereditary, i­ ntoxication, and the transformation of certain neuroses, 28

History of Developments in Understanding Abnormal Behavior

Copyright American Psychological Association. Not for further distribution.

in the 19th century (e.g., Humean models appear in Bolton & Hill, 1996, Chap. 7, and Wulff, Pedersen, & Rosenberg, 1986, Chap. 5). Linear cause–effect models are still the rule, and little attention has been paid to the original contributions of Jackson or Monakow. Writers on internal mechanisms: Jackson and Meynert.  During the second half of the 19th century, the concept of mechanism itself started to change, particularly in biology (Boirel, 1982) and medicine, where it was defined as “the mode in which an act or a series of acts is performed, as the mechanism of respiration or of parturition” (Power & Sedgwick, 1892). The waning of vitalism, that is, of the view that life resulted from the interaction between mechanisms catalyzed by the presence of an ineffable organizational principle, led thinkers to viewing mechanisms themselves as the final object of research: “Mechanism is the view that every biological event is a pattern of non-biological occurrences” (Beckner, 1966, p. 251). This led to the view that anatomy, physiology, and biochemistry were the fundamental purveyors of explanation in medicine and, hence, psychiatry. From then on, mechanism and process started to be used as synonyms (Auroux, 1990, p. 1582; Rosenberg, 1985, pp. 62–68). Theodor Meynert’s (1833–1892) view of mental illness was based on the assumptions that (a) all psychological processes had an organic basis (supporting a primitive form of eliminative materialism; Churchland, 1993); (b) the brain was organized on the basis of reflex arcs (both innate and acquired; Fearing, 1930); (c) because they coordinated and stored information11 association pathways12 were central to the organization of the human brain; and (d) blood flow (Whitehouse, 1985) had a crucial effect on the regulation of brain function (Meynert, 1885). These ideas also influenced Freud13 and Wernicke.

The surface similarity between Meynert’s language and current neuroscientific thinking has led some to see him as a precursor (Whitehouse, 1985). However, claims that mental disorders are disorders of the brain or that blood flow is relevant to brain function mean little unless they are anchored to a physiopathological theory. In this regard, it is sobering to remember that at the time of Meynert, the concept of neuron had not yet developed and that Lockean associationism has little to do with the current concept of neural networks. It is more interesting to think of Meynert as having been a precursor of the rhetorical language of neuroscience, which, as much in his hands then as in those of others now, deftly uses metaphors and other devices to persuade others of its ineluctable truth (Lesky, 1976, p. 338).14 More than most alienists, Meynert disregarded external (whether predisposing or efficient) causal factors of insanity in favor of internal mechanisms (synchronic causality). In this regard, it has been claimed that the explanatory system in Meynert does not really seek to establish a cause-effect relationship. . . . He simply states how psychological phenomena appear as the brain changes its structure and function. The crux of his doctrine was that, in opposition to Griesinger in whom there are two separate groups of phenomena, physical and psychological, Meynert considers all these phenomena and meaning exactly the same so that he does not have to explain at all how the psychological is born out of the physical. (LévyFriesacher, 1983, pp. 32–33) Hughlings Jackson (1835–1911) was an English neurologist (Critchley & Critchley, 1998;

The idea that “association” pathways were crucial to human mentation, and the belief that their pathology led to psychiatric disorder, was developed by Meynert’s disciple, Karl Wernicke.

11

In this context, the notion of association is central to the association psychology movement. Since John Locke, associationism has also been an important mechanism within philosophical empiricism. During the 19th century, associationism was popular among alienists (Claparède, 1903; Rapaport, 1974; Warren, 1921).

12

On the complex relationship between Meynert and Freud, see Wyss (1966, pp. 101–103) and Lévy-Friesacher (1983).

13

Meynert used his rhetorical skills to get research money and promote his career. On the strength of his anatomical discoveries but without having any clinical experience, he was appointed to the Vienna chair of clinical psychiatry. This caused much friction with the local asylum psychiatrists. Krafft-Ebing, his replacement, tellingly wrote, “The results of research in related fields will be of value to psychiatry, but true psychiatry’s progress will only result from unchangeable and unconditional observation and description of the clinical phenomena” (Lesky, 1976, p. 344).

14

29

Berrios and Marková

Copyright American Psychological Association. Not for further distribution.

Dewhurst, 1982; López Piñero, 1973) whose ideas about madness, based on speculation born out of the observation of cases with epilepsy, language deficits, and stroke, were to have great influence on late 19th-century continental psychiatry and psychology (Balan, 1989; Delay, 1957; Evans, 1972; Rouart, 1950) but very little on British psychiatry (Berrios, 1977; Stengel, 1963). Jackson (1894) did not believe in the existence of mental disorders as psychological phenomena: In every insanity there is a morbid affection of more or less of the highest cerebral centres or, synonymously, of the highest level of evolution of the cerebral subs-system, or, again, synonymously, of the highest level of evolution of the cerebral sub-system, or again, synonymously, of the anatomical substrata, or physical basis of consciousness. (as cited in Berrios, 2001, p. 360) Anatomical lesions (dissolutions) led to disappearance of function (negative symptoms) and also to the release of function in other structures (positive symptoms; Berrios, 1985). According to Jackson (1894), differences between the insanities could be explained in terms of four factors: “1) The depths of dissolution of the highest nerve centres; 2) the type of person that underwent the dissolution, 3) the rate of the dissolution, and 4) bodily state in the person undergoing the dissolution” (p. 617). Of these four factors of insanities, only the second is not a synchronic mechanism, that is, one that acting in unison with others would lead to a particular type of mental disorder. Interestingly enough, of all four factors, the one that Jackson neglected to explore was the second, that is, the one that carried historical events acting as efficient causes.

20th Century Wernicke.  Because of his originality and clinical sensitivity, Karl Wernicke (1848–1905) must be considered one of the most important psychiatrists of the early 20th century (Lanczik, 1988). Had he

not died at a young age, psychiatry would now live in a Wernickian world because his views on classification and the generation of mental symptoms were, arguably, far superior to Kraepelin’s. He offered a unitary model encompassing all brain-related diseases, whether psychiatric or neurological; an original neuropsychological model; and, based on the latter, a pathophysiological account to explain the generation of madness (an account that was absent in Kraepelin’s work; Hoff, 1995; Kraepelin, 1896). Central to Wernicke’s model was the idea that the human brain was endowed with a system of neural projection and (transcortical) association fibers that acted as the organ of both cognitive functions and consciousness. Lesions in different sites in the projection fibers would give rise to different neurological diseases. Pathology of the association system would generate mental illness. Wernicke’s organ of association is redolent of the current concept of neural network (Stein & Ludik, 1998). Monakow: Chronogenetic localization and diaschisis.  An imaginative neuropathologist and neurologist, Constantin von Monakow (1853–1930; Monakow, 1970) authored three brilliant books and founded three journals. Affected by the Great War, Monakow withdrew into philosophy, history, and religion (Monakow, 1916/1925). Together with R. Mourgue, a French psychiatrist and historian of science, he wrote one of the most important (and neglected) books on psychopathology in the 20th century (Monakow & Mourgue, 1928). They start by proposing the notion of horme, that is, the tendency of all living beings to develop all their genetic ˛ potential. From the Greek (ορµη, meaning “impulsion,” i.e., what sets something in movement), horme was a “property of the living protoplasm” (Monakow & Mourgue, 1928, p. 33). In the human, horme expressed itself in the instincts that subserved the preservation of each bodily organ, development, the species, society, and culture and religion (Monakow & Mourgue, 1928, pp. 36–37). In each individual, horme is governed by syneidesis,15 that is, by a regulating principle. Horme and syneidesis

Although their choice of the Greek term syneidesis should be considered as infelicitous on account of its associated meaning of consciousness and conscience (Balibar, 2004), Monakow and Mourgue (1928) were aware of the danger: “Is it legitimate to introduce in a scientific model something which derives from the sphere of values? . . . To us philosophical dogma does not matter . . . the important thing is whether including a value concept improves our understanding of the phenomena” (pp. 95–96).

15

30

Copyright American Psychological Association. Not for further distribution.

History of Developments in Understanding Abnormal Behavior

govern the spatiotemporal context in which all biological processes (structure and function) operate. Hence, they are subjected to c­ hronogenetic ­localization and to diaschisis. Based on Semon’s (1908; Schacter, 1982) concept of engram, chronogenetic localization introduces time as a dimension in neuropsychiatry. Functions (e.g., movement) should be considered as processes unfold in time according to a specific kinetic melody. Hence, processes (i.e., brain functions) are not localized in specific sites (i.e., in space alone) but also in time. It would be equally erroneous to try to localize mental symptoms in specific brain addresses. Monakow and Mourgue (1928) believed that chronogenetic localization was a late acquisition in evolutionary time and thus regarded it as a complex but unstable mechanism. One of the practical implications of this important concept is that cross-sectional studies are utterly inadequate to study mental symptoms. These have to be studied as they unfold longitudinally according to their own kinetic melody. For example, a hallucination will only be understood when an entire series, lasting hours or days, has been studied. Studies seriatim provide clinical information that may be more important than the phenomenological features of one episode alone, such as modulations in intensity, changes in imagery, accompanying emotions, and so forth. From an etiological viewpoint, knowledge of longitudinal variation should provide more information about the brain concomitants of mental symptoms than the static snapshots of neuroimaging or other devices. The concept of diaschisis (διασχι′ζω, meaning “I separate at the distance”) refers to sudden and reversible clinical phenomena seen in the wake of the shock caused by trauma to the central nervous system. The defining element of the symptoms caused by diaschisis is that they cannot be explained in terms of focalized lesions. This is why, for example, in hemiplegia, some of the functional deficits are not explained by the focal lesion itself. The mechanism of inhibition differs from diaschisis in that the former results from the activity of known nervous connections. When applied to psychiatry, the concept of diaschisis raises the question of

whether all mental symptoms need to have a specific and direct brain localization. Other narratives.  The changes in the views on the epistemology of madness that started during the 19th century came to fruition during the 20th century. Mental disorders (so-called by then) were to be considered as (a) natural kinds sited in the brain, (b) existing within a temporal–spatial framework, and (c) susceptible to being classified according to external features, etiology, or both. However, inspired by the new philosophies developing during the early 20th century in continental Europe, particularly Jacksonism, hermeneutics, and phenomenology, many challenged the conventional neurobiological narrative of madness. Among its critics were the new French clinical psychologists represented by writers such as Janet, Ribot, and Dumas (Berrios, 1988); Freud and his followers; and clinical phenomenologists (Halling & Nill, 1995). Freudian ideas posed an important challenge to conventional psychiatry. Although Freud did not call into question the old linear causal models, nor the relevance of the brain in many cases of madness, from an epistemological viewpoint his contribution is to be found in his views on the nature and meaning of the mental symptom itself. Until his time, the sign–signifier structure of symptoms had been predominant. Part of this model was the belief that experiential content of the symptom reflected the functionality of the neural substratum (i.e., lesions of occipital cortex gave rise to perceptual disorders). For Freud, the experiential content of the symptom was allegorical or symbolic and did not reflect the functionality of its putative anatomical substratum. To understand and manage the symptoms in question, Freud proposed a system of structures and relationships whose emotional valences were determined by the past of each sufferer. The phenomenologies are a family of philosophies that developed out of the work of Brentano, Husserl, and others. In historical terms, they offered new ways of conceiving the ontology and epistemology of reality in general and of mental complaints in particular. In some cases (such as Binswanger’s), 31

Copyright American Psychological Association. Not for further distribution.

Berrios and Marková

alliances were formed between phenomenology and psychoanalysis (Halling & Nill, 1995). The specific contribution of phenomenology to psychiatry remains unclear. The conventional claim is that it gave psychiatry a special form of empathetic descriptivism (Berrios, 1992). However, since the 19th century, psychiatry had to develop a descriptive method to gain enough subjective information to construct clinical psychopathology. Indeed, before Jaspers there was already a rich descriptive tradition in European psychopathology, as illustrated by the work of Emminghaus, Morselli, Störring, Chaslin, Séglas, and so forth, whose influence can actually be detected in Jaspers’s 1913 book (Berrios, 1992). A similar descriptivist tradition can be found in the work of Dilthey (1977; Caparrós, 1986), who was not a phenomenologist (Makkreel & Scanlon, 1987) and whose ideas also had an influence on Jaspers. Later writers have suggested that phenomenology opens an intermediate space between neuropsychological narratives, occupied in describing changes occurring in the brain, and the molar level of diagnosis, that is, the complaints themselves (Fuchs, 2010). Such a mediating role would be discharged by phenomenology with the help of putative conceptual structures such as temporality, self, embodiment, and so forth. This interesting suggestion needs further clarification.

21st Century The first two decades of the 21st century have added little to the epistemology (and thereby to the etiology) of madness. Neuroscientific narratives predominate, and through an interesting alliance with the new scientific journalism, they control public opinion. This leads to regular announcements of imminent breakthroughs, both causal and therapeutic. Increased public expectations put additional pressure on funding bodies to continue research along the same lines. Related industries, pharmaceutical, neuroimaging, and medical devices (now popular in the field of brain stimulation), lobby in the same direction. The more cautious approach followed by seasoned geneticists and neuroimagers is rarely, if ever, taken into account (Marková & Berrios, 2015). In this neuroscientific 32

frenzy, alternative ways of conceptualizing madness and psychological treatments have little chance of being heard. Even the predominant analytical philosophy of psychiatry (e.g., Fulford, Thornton, & Graham, 2006) acts as a champion and justifier of the neuroscientific narrative, rather than trying to audit some of its wilder claims. With minor success, other groups have been doing this auditing job for some time, and alternative epistemological approaches have developed that take concepts such as subjectivity, empathy, and cultural context more seriously (e.g., Berrios, 2000; Berrios & Marková, 2002, 2017; Blanc, 1998; Hundert, 1989; Natanson, 1969; Palem, 1997). Concerning causal models of madness, there has also been very little growth. Current advances in the philosophy of causality (Tanney, 2013) do not seem to have percolated down to medicine or psychiatry. A mixture of inner mechanisms and efficient causes remains the official way in which 21st-century psychiatrists understand madness. The internal mechanisms model fits well with the neuroscientific narrative, and they support each other. The development of new ways of explaining and understanding madness, including the possibility that moral efficient causes are crucial to the formation of madness, could force the issue and stimulate the search for more successful alternative therapies. There is little interest in this field, however, as shown by the fact that (apart from psychoanalysis), official psychiatry does not seem to be interested in the possibility that reasons (as efficient causes) may be a cause of madness. Given that psychiatry is dedicated to helping people with mental affliction, the fact that one (not very successful) narrative predominates to the detriment of all others could be construed as a breach in the ethics of epistemology. CONCLUSION It is evident from this brief exploration into the history of developments in understanding abnormal behavior that a straightforward account is not possible. Simply unpacking the terms presented here yields difficulties because their individual meanings have evolved at different rates and in relation to

Copyright American Psychological Association. Not for further distribution.

History of Developments in Understanding Abnormal Behavior

different contexts. For example, because of changes in the epistemology of statistics and psychology, the words abnormal and behavior only gained their current meaning during the early 20th century. Hence the phrase abnormal behavior would have had an entirely different meaning before 1900. This raises questions as to whether the phrase abnormal behavior should be used to capture accounts of madness before that date. Should one be prepared to accept the historiographical cost involved in anachronistically applying current concepts such as norm, quantitative deviance, objective deportment, and so forth to earlier accounts of madness? Likewise, there is the concept of understanding, whose meaning changed during the late 19th century after the work of Dilthey, Windelband, Rickert, and others. Should the term be used in its pre- or post-Diltheyian sense? Should perhaps a neutral sense of understanding be sought specially for this chapter? The problem is that such a neutral sense is likely to be unavailable, for all current usages have been touched by Dilthey’s influence and evoke epistemological acts such as accounting, explaining, and so forth. Regardless of these changes, should the new meaning of understanding be used to deal with accounts of madness before 1800? Finally, currently, the term developments is journalistic parlance for “discoveries,” that is, scientific findings believed to have great impact. Within science itself, and in keeping with the old biological metaphor from which it originates, development has a narrower sense and refers to knowledge claims not yet ascertained. If this is the case, what accounts should qualify as developments: Only those that are in keeping with the present such as neuroscientific developments? What about religious or demoniacal accounts of madness? Raising such questions in the conclusion serves to emphasize two main issues in the writing of this chapter. First, as already alluded to earlier, they highlight some of the complexities involved in tracing the origins and changes in meanings that underlie the concepts under exploration. In this way, they help to clarify the constraints under which such accounts can be understood—in the context of changing assumptions and the inevitable discontinuities. Second, they also draw attention to the

necessary selective process that is inherent to the creation of a historical narrative.

References Aarsleff, H. (1982). From Locke to Saussure. London, England: Athlone Press. Anonymous. (1691). A New English dictionary shewing the etymological derivation of the English tongue. London, England: Timothy Childe. Anscombe, G. E. M. (1957). Intention. Oxford, England: Blackwell. Apel, K. O. (2001). Verstehen [Understanding]. In J. Ritter J (Ed.), Historisches Wörterbuch der Philosophie (Vol. 11, pp. 918–938). Basel, Switzerland: Schwabe. Aristotle. (1984). The complete works of Aristotle (J. Barnes, Ed.; Vol. 2). Princeton, NJ: Princeton University Press. Armstrong, D. M. (1983). What is a law of nature? Cambridge, England: Cambridge University Press. Auroux, S. (Ed.). (1990). Les notions philosophiques [Philosophical notions] (Vol. 2). Paris, France: Presses Universitaires de France. Bacon, F. (1905a). De augmentis scientiarum [On the advancement of learning]. In J. M. Robertson (Ed.), The philosophical works of Francis Bacon (pp. 413–638). London, England: Routledge. Bacon, F. (1905b). Novum organum [New instrument of science]. In J. M. Robertson (Ed.), The philosophical works of Francis Bacon (pp. 232–301). London, England: Routledge. Balan, B. (1989). Les Fondements psychologiques de la notion d’automatisme mental chez John Hughlings Jackson [The psychological foundations of the notion of mental automatism in John Huglings Jackson]. L’Information Psychiatrique, 69, 610–619. Balibar, E. (2004). Conscience. In B. Cassin B (Ed.), Vocabulaire Européen des philosophies (pp. 260–273). Paris, France: Seuil. Barrett, J. A., & Stanford, P. K. (2006). Prediction. In S. Sarkar & J. Pfeiffer (Eds.), Philosophy of science: An encyclopaedia (pp. 585–598). London, England: Routledge. Battie, W. (1758). A treatise on madness. London, England: J. Whiston & B. White. Bayle, A. L. J. (1826). Traité des maladies du cerveau et de ses membranes [Treatise of diseases of the brain and its membranes]. Paris, France: Gabon. Beckner, M. O. (1966). Mechanisms in biology. In P. Edwards (Ed.), The encyclopaedia of philosophy (Vol. 5, pp. 250–252). New York, NY: Macmillan. 33

Berrios and Marková

Beebee, H. (2006). Hume on causation. Oxford, England: Oxford University Press. Bercherie, P. (1980). Les Fondements de la clinique: Histoire et structure du savoir psychiatrique [The foundations of the clinic: History and structure of psychiatric knowledge]. Paris, France: La Bibliothèque d’Ornicar. Berrios, G. E. (1977). Henri Ey, Jackson, et les idées obsédantes [Henri Ey, Jackson, and obsessive ideas]. L’Évolution Psychiatrique, 42, 685–699.

Copyright American Psychological Association. Not for further distribution.

Berrios, G. E. (1985). Positive and negative symptoms and Jackson. A conceptual history. Archives of General Psychiatry, 42, 95–97. http://dx.doi.org/ 10.1001/archpsyc.1985.01790240097011 Berrios, G. E. (1988). Historical background to abnormal psychology. In E. Miller & P. J. Cooper (Eds.), Adult abnormal psychology (pp. 26–51). Edinburgh, Scotland: Churchill Livingstone. Berrios, G. E. (1992). Phenomenology, psychopathology and Jaspers: A conceptual history. History of Psychiatry, 3, 303–327. http://dx.doi.org/10.1177/ 0957154X9200301103 Berrios, G. E. (1996). The history of mental symptoms: Descriptive psychopathology since the 19th century. http://dx.doi.org/10.1017/CBO9780511526725 Berrios, G. E. (1999a). Classic text no. 37: J. C. Prichard and the concept of “moral insanity.” History of Psychiatry, 10, 111–126. http://dx.doi.org/10.1177/ 0957154X9901003706 Berrios, G. E. (1999b). Classifications in psychiatry: A conceptual history. Australian and New Zealand Journal of Psychiatry, 33, 145–160. http://dx.doi.org/ 10.1046/j.1440-1614.1999.00555.x Berrios, G. E. (2000). Historical development of ideas about psychiatric aetiology. In M. G. Gelder, J. J. López-Ibor, & N. Andreasen (Eds.), New Oxford textbook of psychiatry (pp. 147–153). Oxford, England: Oxford University Press. Berrios, G. E. (2014). J. H. Pons on “Sympathetic insanity.” History of Psychiatry, 25, 364–376. http:// dx.doi.org/10.1177/0957154X14541919 Berrios, G. E., & Marková, I. S. (2002). Biological psychiatry: Conceptual issues. In H. D’Haenen, J. A. den Boer, & P. Willner (Eds.), Biological psychiatry (pp. 3–24). http://dx.doi.org/10.1002/0470854871.chi Berrios, G. E., & Marková, I. S. (2017). The epistemology and classification of “madness” since the 18th century. In G. Eghigian (Ed.), Routledge history of madness and mental health (pp. 115–134). London, England: Routledge. Besançon, S. (1997). La Philosophie de Cabanis: Une réforme de la psychiatrie [The philosophy of Cabanis: A reform of psychiatry]. Paris, France: Les Empêcheurs de Penser en Rond.

34

Blanc, C. J. (1998). Psychiatrie et penseé philosophique [Psychiatry and philosophical thought]. Paris, France: L’Harmattan. Boirel, R. (1982). Le Mécanisme [Mechanism]. Paris, France: Presses Universitaires de France. Bolton, D., & Hill, J. (1996). Mind, meaning and mental disorder: The nature of causal explanation in psychology and psychiatry. Oxford, England: Oxford University Press. Bowler, P. J. (1975). The changing meaning of “evolution.” Journal of the History of Ideas, 36, 95–114. http://dx.doi.org/10.2307/2709013 Brochin, L. (1887). Étiologie médicale [Medical etiology]. In A. Dechambre & L. Lereboullet L. (Eds.) Dictionnaire encyclopédique des sciences médicales (Vol 36, pp. 340–353). Paris, France: Masson. Burckhardt, R. W. (1977). The spirit of system: Lamarck and evolutionary biology. Cambridge, MA: MIT Press. Cabanis, P. J. G. (1981). On the relationship between the physical and moral aspect of man (G. Mora, Ed., & M. D. Saidi, Trans.; Vols. 1–2). Baltimore, MD: Johns Hopkins University Press. Canguilhem, G. (1978). The normal and the pathological. http://dx.doi.org/10.1007/978-94-009-9853-7 Caparrós, A. H. (1986). Ebbinghaus: Un funcionalista investigador tipo dominio [Ebbinghaus: A functional domain type researcher]. Barcelona, Spain: Publicacions Universitat de Barcelona. Carlson, E. T., & Simpson, M. M. (1969). Models of the nervous system in eighteenth century psychiatry. Bulletin of the History of Medicine, 43, 101–115. Cassin, B. (2004). Raison [Reason]. In B. Cassin (Ed.), Vocabulaire Européen des philosophies (pp. 1059–1060). Paris, France: Seuil. Cauwenbergh, L. (1991). J. Chr. A. Heinroth (1773–1843): A psychiatrist of the German romantic era. History of Psychiatry, 2, 365–383. http://dx.doi.org/10.1177/ 0957154X9100200802 Caxton, W. (1890). Eneydos (M. T. Culley, Ed.). London, England: Kegan & Paul. (Original work published 1490) Charland, L. C. (2014). John Locke on madness: Redressing the intellectualist bias. History of Psychiatry, 25, 137–153. http://dx.doi.org/10.1177/ 0957154X13518719 Chazaud, J. (1993). Cabanis et la production de la pensée [Cabanis and the production of thought]. L’Information Psychiatrique, 69, 539–544. Churchland, P. M. (1993). Eliminative materialism and propositional attitudes. In S. M. Christensen & D. R. Turner (Eds.), Folk psychology and the philosophy of mind (pp. 42–62). Hillsdale, NJ: Erlbaum.

History of Developments in Understanding Abnormal Behavior

Claparède, É. (1903). L’association des idées [The association of ideas]. Paris, France: Doin. Clarke, E., & Jacyna, L. S. (1987). Nineteenth-century origins of neuroscientific concepts. Berkeley: University of California Press. Clarke, E., & O’Malley, C. D. (1996). The human brain and spinal cord (2nd ed.). San Francisco, CA: Norman.

Copyright American Psychological Association. Not for further distribution.

Coles, E. (1677). An English dictionary. London, England: Peter Parker. Conry, Y. (1982). Thomas Willis où le premier discours rationaliste en pathologie mentale [Thomas Willis or the first rationalist discourse in mental pathology]. L’Information Psychiatrique, 58, 313–323. Constant, F. M. C. (1970). Introduction à la vie et à l’œuvre de Bénédict-Augustin Morel [Introduction to the life and work of Bénédict-Augustin Morel]. Paris, France: Thèse de Paris. Coury, C. (1971). La méthode anatomo-clinique et ses promoteurs en France: Corvisart, Bayle, Laennec [The anatomo-clinical method and its promoters in France: Corvisart, Bayle, Laennec]. La Medecine en France, 1, 13–22. Cranston, M. (1967). Francis Bacon. In P. Edwards (Ed.), The encyclopedia of philosophy (Vol. 1, pp. 235–240). London, England: Macmillan. Critchley, M., & Critchley, E. A. (1998). John Hughlings Jackson: Father of English neurology. Oxford, England: Oxford University Press. Cullen, W. (1785). Synopsis nosologiæ methodicæ [Nosology of diseases] (4th ed., Vol. 1). Edinburgh, Scotland: William Creech. Darwin, C. (1883). The descent of man (2nd ed.). London, England: John Murray. (Original work published 1874) Davidson, D. (2001). Essays on actions and events (2nd ed.). http://dx.doi.org/10.1093/0199246270.001.0001 Déchambre, E. (1883). Déterminisme [Determinism]. In E. Dechambre & L. Lereboullet (Eds.), Dictionnaire Encyclopédique des Sciences Médicales (Vol. 28, pp. 435–449). Paris, France: Masson. Delay, J. (1957). Jacksonism and the works of Ribot. Archives of Neurology and Psychiatry, 78, 505–515. http://dx.doi.org/10.1001/ archneurpsyc.1957.02330410069011 Dewhurst, K. (1966). Dr. Thomas Sydenham (1624–1689): His life and original writings. Berkeley: University of California Press. Dewhurst, K. (1982). Hughlings Jackson on psychiatry. Oxford, England: Sandford. Dijksterhius, E. J. (1961). The mechanization of the world picture. Oxford, England: Oxford University Press.

Dilthey, W. (1977). Descriptive psychology and historical understanding (R. M. Zaner & K. L. Helges, Trans.). The Hague, the Netherlands: Nijhoff. Dilthey, W. (2000). Allgemeine Geschichte der Philosophie: Vorlesungen, 1900–1905 [General history of philosophy: Lectures, 1900–1905] (G. Gebhardt & H. U. Lessing, Eds.). Göttingen, Germany: Vandenhoeck & Ruprecht. Droixhe, D. (1978). La Linguistic et l’appel de l’histoire (1600–1800) [Linguistics and the call of history (1600–1800)]. Geneva, Switzerland: Droz. Droysen, J. G. (1977). Historik: Vorlesungen über Enzyklopädie und Methodologie der Geschichte [History: Lectures on encyclopedia and methodology of history]. Munich, Germany: R. Oldenbourg. (Original work published 1936) Duplay, S. (1870). Anomalie [Anomaly]. In A. Dechambre (Ed.), Dictionnaire encyclopédique des sciences médicales (Vol. 5, pp. 221–222). Paris, France: Masson. Engelhardt, H. T., Jr. (1975). John Hughlings Jackson and the mind-body relation. Bulletin of the History of Medicine, 49, 137–151. Esquirol, E. (1838). Des maladies mentales [Mental illness] (Vol. 1). Paris, France: Baillière. Evans, P. (1972). Henri Ey’s concepts of the organization of consciousness and its disorganization: An extension of Jacksonian theory. Brain: A Journal of Neurology, 95, 413–440. http://dx.doi.org/10.1093/ brain/95.2.413 Fearing, F. (1930). Reflex action: A study in the history of physiological psychology. Baltimore, MD: Williams & Wilkins. Feest, U. (Ed.). (2010). Historical perspectives on erklären and verstehen. http://dx.doi.org/10.1007/ 978-90-481-3540-0 Feuchtersleben, E. von (1847). The principles of medical psychology (H. E. Lloyd & B. G. Babington, Trans.). London, England: Sydenham Society. (Original work published 1845) Feuchtersleben, E. von (1854). The dietetics of the soul (7th ed.). New York, NY: C. S. Francis. (Original work published 1838) Frank, R. G. (1980). Harvey and the Oxford physiologists. Berkeley: University of California Press. Friedlander, R. (1973). B. A. Morel and the development of the theory of Dégénérescence (Unpublished doctoral dissertation). San Francisco: University of California. Fuchs, T. (2010). Phenomenology and psychopathology. In S. Gallagher & D. Schmicking (Eds.), Handbook of phenomenology and cognitive science (pp. 546–573). http://dx.doi.org/10.1007/978-90-481-2646-0_28

35

Berrios and Marková

Fulford, K. W. M., Thornton, T., & Graham, G. (2006). Oxford textbook of philosophy and psychiatry. Oxford, England: Oxford University Press.

Hobbes, T. (1996). Leviathan (R. Tuck, Ed.). Cambridge, England: Cambridge University Press. (Original work published 1651)

Gert, B. (1996). Hobbes’s psychology. In T. Sorell (Ed.), The Cambridge companion to Hobbes (pp. 157–174). http://dx.doi.org/10.1017/CCOL0521410193.008

Hoeldtke, R. (1967). The history of associationism and British medical psychology. Medical History, 11, 46–65. http://dx.doi.org/10.1017/S002572730001173X

Glare, P. G. W. (1968). Oxford Latin dictionary. Oxford, England: Clarendon Press.

Hoff, P. (1995). Kraepelin. In G. E. Berrios & R. Porter R (Eds.), A history of clinical psychiatry (pp. 261–279). London, England: Athlone Press.

Copyright American Psychological Association. Not for further distribution.

Glass, B., Temkin, O., & Straus, W. L. (1968). Forerunners of Darwin: 1745–1859. Baltimore, MD: Johns Hopkins University Press.

Holy-Oke, F. (1659). John Riders dictionary corrected and augmented. London, England: Andrew Crooke.

Glennan, S. (2006). Explanation. In S. Sarkar & J. Pfeiffer (Eds.), Philosophy of science: An encyclopaedia (pp. 275–287). London, England: Routledge.

Hume, D. (2007). An enquiry concerning human understanding. Oxford, England: Oxford University Press. (Original work published 1756)

Greene, J. C. (1962). Biology and social theory in the nineteenth century: Auguste Comte and Herbert Spencer. In M. Claggett (Ed.), Critical problems in the history of science (pp. 419–446). Madison: University of Wisconsin Press.

Hundert, E. M. (1989). Philosophy, psychiatry and neuroscience. Oxford, England: Clarendon Press.

Griesinger, W. (1867). Mental pathology and therapeutics (C. L. Robertson & J. Rutherford, Trans.). London, England: New Sydenham Society. (Original work published 1845) Gruner, R. (1981). Progressivism and historicism. Clio, 10, 279–290. Halling, S., & Nill, J. D. (1995). A brief history of existentialphenomenological psychiatry and psychotherapy. Journal of Phenomenological Psychology, 26, 1–45. http:// dx.doi.org/10.1163/156916295X00024 Hartley, D. (1834). Observations on man, his frame, his duty, and his expectations (6th ed.). London, England: Thomas Tegg. (Original work published 1749)

Imbault-Huart, M. J. (1981). Bayle, Laennec et la méthode anatomo-clinique [Bayle, Laennec and the anatomo-clinical method]. Revue de Palais de la Découverte, 22, 79–90. Jackson, J. H. (1894). The factors of insanities. Medical Press and Circular, ii, 615–623. Jackson, J. H., & Berrios, G. E. (2001). The factors of insanities. History of Psychiatry, 12, 353–359. http:// dx.doi.org/10.1177/0957154X0101204705 Jacob, F. (1974). The logic of living systems: A history of heredity. London, England: Allen Lane. Janet, P. (1900). Final causes (2nd ed.; W. Affleck, Trans.). New York, NY: Scribner. Jordanova, L. J. (1984). Lamarck. Oxford, England: Oxford University Press.

Hecht, L. (1884). Sympathie [Sympathy]. In A. Dechambre (Ed.), Dictionnaire encyclopédique des sciences médicales (Vol. 13, 3rd Series, pp. 670–684). Paris, France: Asselin & Masson.

Kahlbaum, K. L., & Berrios, G. E. (1996). Die Gruppiring der psychischen Krankheiten . . . Part III [The classification of mental disorders . . . Part III]. History of Psychiatry, 7, 167–181.

Hegel, G. W. F. (1990). Enciclopedia de las ciencias filosóficas [Encyclopedia of philosophical sciences] (6th ed.; trans. unknown). México City, Mexico: Editorial Porrúa. (Original work published 1817)

Kelsen, I. (1949). General theory of the law and state. Cambridge, MA: Harvard University Press.

Heinroth, J. C. (1975). Textbook of disturbances of mental life (J. Schmorak, Trans.; Vols. 1–2). Baltimore, MD: Johns Hopkins University Press. (Original work published 1818)

Koons, R. C. (2000). Realism regained: An exact theory of causation, teleology, and the mind. Oxford, England: Oxford University Press.

Herbert, G. B. (1989). Thomas Hobbes. Vancouver, British Columbia, Canada: University of British Columbia Press. Hobbes, T. (1989). Metaphysical writings: Elements of philosophy concerning the body (M. W. Calkins, Ed.). La Salle, IL: Open Court. Hobbes, T. (1991). Man and citizen: De Homine and De Cive. In B. Gert (Ed.). Indianapolis, IN: Hackett. (Original work published 1642) 36

Koerner, E. F. K. (1982). Ferdinand de Saussure. Madrid, Spain: Gredos.

Kottler, M. J. (1985). Charles Darwin and Alfred Russel Wallace: Two decades of debate over natural selection. In D. Kohn (Ed.), The Darwinian heritage (pp. 367–432). Princeton, NJ: Princeton University Press. Koutouvidis, N., Marketos, S. G., & Beveridge, A. (1995). The contribution of Thomas Sydenham (1624–1689) to the evolution of psychiatry. History of Psychiatry, 6, 513–520. http://dx.doi.org/10.1177/ 0957154X9500602408

History of Developments in Understanding Abnormal Behavior

Kraepelin, E. (1896). Der psychologische Versuch in der Psychiatrie [The psychological experiment in psychiatry]. Psychologische Arbeiten, 1, 1–91. Lamarck, J. B. (1988). Système analytique des connaissances positives de l’homme [Analytical system of positive human knowledge]. Paris, France: Presses Universitaires de France. (Original work published 1820) Lanczik, M. (1988). Der Breslauer Psychiater Carl Wernicke [The Breslau psychiatrist Carl Wernicke]. Sigmaringen, Germany: Jan Thorbecke.

Copyright American Psychological Association. Not for further distribution.

Landre-Beauvais, A. J. (1813). Sémiotique, ou traité des signes de maladies [Semiotics, or treatise of signs of diseases]. Paris, France: Brosson. Larousse, P. (1866). Grand dictionnaire universel du XIXe siècle [Great universal dictionary of the 19th century] (Vol. 1). Paris, France: Administration du Grand Dictionnaire Universel. Laugier, S. (2004). Behaviour. In B. Cassin (Ed.), Vocabulaire Européen des philosophies [European vocabulary of philosophies] (pp. 175–179). Paris, France: Seuil. Lesky, E. (1976). The Vienna Medical School of the 19th century. Baltimore, MD: Johns Hopkins University Press. Lévy-Friesacher, C. (Ed.). (1983). Meynert-Freud “L’Amentia.” Paris, France: Presses Universitaires de France. Liddell, H. G., & Scott, R. (1996). Greek-English lexicon. Oxford, England: Clarendon Press. Linné, C. (1763). Genera morborum in auditorum usum [Classes of diseases]. Uppsala, Sweden: Christ. Erh. Steinert. Linné, C. (1766). Clavis medicinæ duplex, exterior et interior [Two keys to medicine]. Stockholm, Sweden: Laurentiii Salvii. Locke, J. (1690). An essay concerning humane understanding: In four books. London, England: Thomas Basset. López Piñero, J. M. (1973). John Hughlings Jackson (1835–1911): Evolucionismo y neurología [John Hughlings Jackson (1835–1911): Evolutionism and neurology]. Madrid, Spain: Editorial Moneda. Lovejoy, A. O. (1960). The great chain of being. New York, NY: Harper. (Original work published 1936) Lyell, C. (1873). The antiquity of man (4th ed.). London, England: Murray. Makkreel, R. A., & Scanlon, J. (1987). Dilthey and phenomenology. Washington, DC: University Press of America.

P. Zachar, D. S. Stoyanov, M. Aragona, & A. Jablensky (Eds.), Alternative perspectives on psychiatric validation (pp. 112–127). Oxford, England: Oxford University Press. Martin, M. (2000). The uses of understanding in the social sciences. Piscataway, NJ: Transaction. McDougall, W. (1912). Psychology: The study of behaviour. http://dx.doi.org/10.1037/10542-000 McGuinness, B. (Ed.). (1987). Unified science (Vienna Circle monograph series). Dordrecht, The Netherlands: Reidel. Meynert, T. (1885). Psychiatry: A clinical treatise on diseases of the fore-brain (B. Sachs, Trans.). New York, NY: Putnam. Mill, J. S. (1843). A system of logic (Vol. 1). London, England: John Parker. Monakow, C. von (1925). The emotions, morality, and the brain (G. Barnes & S. E. Jelliffe, Trans.). Washington, DC: Nervous and Mental Disease Publishing. (Original work published 1916) Monakow, C. von (1970). Vita mea: Mein Leben [My life] (A. W. Gubser & W. H. Ackerknecht, Eds.). Bern, Switzerland: Hans Huber. Monakow, C. von, & Mourgue, R. (1928). Introduction biologique à l’étude de la neurologie et de la psychopathologie [Biological introduction to the study of neurology and psychopathology]. Paris, France: Alcan. Mora, G. (1975). Introduction: Heinroth’s contribution to psychiatry. In J. C. Heinroth (Ed.), Textbook of disturbances of mental life (J. Schmorak, Trans.; Vols. 1–2, pp. ix–lxxv). Baltimore, MD: Johns Hopkins University Press. Morel, B. A. (1852). Études cliniques: Traité théorique et pratique des maladies mentales [Clinical studies: Theoretical and practical treatment of mental illnesses] (Vols. 1–2). Paris, France: Masson. Morel, B. A. (1857). Traité des dégénérescences physiques, intellectuelles, et morales de l’espèce humaine [Treatise of the physical, intellectual, and moral degenerations of the human species]. Paris, France: Baillière. Morel, B. A. (1860). Traité de maladies mentales. Paris, France: Masson. Moulin, A. M. (2004). Étiologie [Etiology]. In D. Lecourt (Ed.), Dictionnaire de la pensée médicale (pp. 446–450). Paris, France: Presses Universitaires de France.

Mannheim, K. (1924). Historismus [Historicism]. Archiv für Socialwissenschaft und Socialpolitik, 52, 1–60.

Mourgue, R. (1931). L’Œvre et la personnalité du Professeur Constantin von Monakow (1853–1930) [The work and personality of Professor Constantin von Monakow (1853–1930)]. L’Encéphale, 26, 417–428.

Marková, I. S., & Berrios, G. E. (2015). Neuroimaging in psychiatry: Epistemological considerations. In

Natanson, M. (Ed.). (1969). Psychiatry and philosophy. http://dx.doi.org/10.1007/978-3-642-87984-5_2 37

Berrios and Marková

Oberg, B. B. (1976). David Hartley and the association of ideas. Journal of the History of Ideas, 37, 441–454. http://dx.doi.org/10.2307/2708808 Ott, W. (2009). Causation and laws of nature in early modern philosophy. http://dx.doi.org/10.1093/ acprof:oso/9780199570430.001.0001 Palem, R. M. (1997). Henri Ey: Psychiatrie et philosophie [Henri Ey: Psychiatry and philosophy]. Paris, France: Rive Droite. Payne, J. F. (1900). Thomas Sydenham. London, England: Fisher Unwin.

Copyright American Psychological Association. Not for further distribution.

Peters, R. (1967). Hobbes. London, England: Peregrine Books. Picard, L. M. F. (1889). Thomas Sydenham, sa vie et ses oeuvres [Thomas Sydenham, his life and works] (Doctoral thesis). Dijon, France: Imprimerie Darantiere. Pinel, P. (1809). Traité médico-philosophique sur l’aliénation mentale [Medical-philosophical treatise on mental alienation] (2nd ed.). Paris, France: Brosson. Postel, J. (1983). La paralysie générale [General paralysis]. In J. Postel & C. Quétel (Eds.), Nouvelle histoire de la psychiatrie (pp. 322–333). Paris, France: Privat. Postel, J. (1996). Pinel. In P. Morel (Ed.), Dictionnaire biographique de la psychiatrie (pp. 195–196). Paris, France: Collection Les Empêcheurs de Penser en Rond. Power, H., & Sedgwick, L. W. (Eds.). (1892). The New Sydenham Society’s lexicon of medicine and the allied sciences (Vol. 4). London, England: New Sydenham Society. Prichard, J. C. (1835). A treatise on insanity and other disorders affecting the mind. http://dx.doi.org/ 10.1037/10551-000 Rapaport, D. (1974). The history of the concept of association of ideas. New York, NY: International Universities Press. Riese, W. (1950). La pensée causal en médecine [Causal thinking in medicine]. Paris, France: Presses Universitaires de France. Roger, J. (1993). Les Sciences de la vie dans la pensée Française du XVIII siècle [Life sciences in French thought of the 18th century] (New ed.). Paris, France: Albin Michel. Rosenberg, A. (1985). The structure of biological science. http://dx.doi.org/10.1017/CBO9781139171724 Rostan, L. (1823). Recherches sur le ramollissement du cerveau [Research on softening of the brain]. Paris, France: Rechet. Rouart, J. (1950). Janet et Jackson [Janet and Jackson]. L’Évolution Psychiatrique, 25, 485–501. 38

Ruben, D. H. (1990). Explaining explanation. http:// dx.doi.org/10.4324/9780203169308 Schacter, D. L. (1982). Stranger behind the engram: Theories of memory and the psychology of science. London, England: Erlbaum. Schurz, G. (2014). Philosophy of science: A unified approach. London, England: Routledge. Semon, R. (1908). Die Mneme als erhaltendes Prinzip im Wechsel des organischen Geschehens [The mneme as a preserving principle in the alternation of organic happenings] (2nd ed.). Leipzig, Germany: Wilhelm Engelman. Starkstein, S. E., & Berrios, G. E. (2015). The “preliminary discourse” to Methodological Nosology, by François Boissier de Sauvages (1772). History of Psychiatry, 26, 477–491. http://dx.doi.org/10.1177/0957154X15602361 Staum, M. S. (1980). Cabanis. http://dx.doi.org/ 10.1515/9781400857029 Stein, D. J., & Ludik, J. (Eds.). (1998). Neural networks and psychopathology. http://dx.doi.org/10.1017/ CBO9780511547195 Stengel, E. (1963). Hughlings Jackson’s influence in psychiatry. British Journal of Psychiatry, 109, 348–355. http://dx.doi.org/10.1192/bjp.109.460.348 Stocking, G. W. (1973). From chronology to ethnology: James Cowles Prichard and British anthropology, 1800–1850. In J. C. Prichard (Ed.), Researches into the physical history of man (pp. ix–cxliv). Chicago, IL: University of Chicago Press. Sydenham, T. (1848). The works of Thomas Sydenham (D. Greenhill, Trans.; Vol. 2). London, England: Sydenham Society. (Original work published 1676) Tanney, J. (2013). Rules, reason and self-knowledge. Cambridge, MA: Harvard University Press. Taylor, F. K. (1982). Sydenham’s disease entities. Psychological Medicine, 12, 243–250. http:// dx.doi.org/10.1017/S0033291700046572 Thouard, D. (2004). Entendement [Understanding]. In B. Cassin (Ed.), Vocabulaire Européen des philosophies (pp. 349–353). Paris, France: Seuil. Tuke, D. H. (Ed.). (1892). A dictionary of psychological medicine (Vol. 2). London, England: Churchill. VandenBos, G. R. (Ed.-in-Chief). (2013). APA dictionary of clinical psychology. Washington, DC: American Psychological Association. Vinchon, J., & Vie, J. (1928). Un Maitre de la neuropsychiatrie au XVII siècle: Thomas Willis (1662–1675) [A master of neuropsychiatry in the 17th century: Thomas Willis (1662–1675)]. Annales Médico-Psychologiques, 86, 109–144. Wahring-Schmidt, B. (1985). Der Junge Wilhelm Griesinger im Spannungsfeld zwischen Philosophie und Physiologie [The young Wilhelm Griesinger in

History of Developments in Understanding Abnormal Behavior

the tension between philosophy and physiology]. Tübingen, Germany: Gunter Narr.

Windelband, W. (1907). Präludien [Preludes] (3rd ed.). Tübingen, Germany: Mohr. Wulff, H. R., Pedersen, S. A., & Rosenberg, R. (1986). Philosophy of medicine. Oxford, England: Blackwell. Wyss, D. (1966). Depth psychology (G. Onn, Trans.). London, England: Allen & Unwin. Yost, R. M., Jr. (1950). Sydenham’s philosophy of science. Osiris, 9, 84–105. http://dx.doi.org/10.1086/368525

Copyright American Psychological Association. Not for further distribution.

Warren, H. C. (1921). A history of association psychology. http://dx.doi.org/10.1037/11522-000 Whitehouse, P. J. (1985). Theodor Meynert: Foreshadowing modern concepts of neuropsychiatric pathophysiology. Neurology, 35, 389–391. http://dx.doi.org/10.1212/ WNL.35.3.389 Williams, E. (2003). A cultural history of medical vitalism in enlightenment Montpellier. London, England: Routledge.

Willis, T. (1685). The London practice of physick. London, England: Thomas Basset.

39

Chapter 3

Diagnosis and Classification of Psychopathology

Copyright American Psychological Association. Not for further distribution.

Thomas A. Widiger and Cristina Crego

Maladaptive and dysfunctional thoughts, emotions, and behaviors are of substantial concern to many different professions (e.g., clinical psychology, psychiatry, nursing, and social work) and agencies (e.g., insurance companies, funding agencies, disability services, the judicial system, and the educational system), the members of which hold a diverse array of beliefs regarding the nature of psychopathology. Yet, the persons within and across these diverse professions and agencies must all work together, communicating in a consistent and meaningful fashion. The primary purpose of an official diagnostic nomenclature is to provide a common language of communication (Kendell, 1975; ­Sartorius et al., 1993). Official diagnostic nomenclatures, however, can be exceedingly powerful, substantially affecting many important social, forensic, clinical, and other professional decisions (Frances, 2013; Hyman, 2010; Kirk, 2005; Wakefield, 2016). An official diagnostic system can govern what constitutes a mental disorder that would qualify for coverage from an insurance company, receive funding for research, justify support within the educational system, or warrant mitigation of criminal responsibility. An official diagnostic manual can also have the appearance of scientific authority, as though everything in the manual has been proven to be correct, accurate, and true. At a more fundamental level, people think in terms of their language. How one thinks about oneself and others is governed by the language that one

uses. The predominant languages of psychopathology for the mental health professions are the fifth edition of the American Psychiatric Association’s (2013) Diagnostic and Statistical Manual of Mental Disorders (DSM–5) and the 10th revision of the World Health Organization’s (WHO; 1992) ICD–10 Classification of Mental and Behavioural Disorders (ICD–10). The 11th revision of the ICD is currently under way and scheduled to be published in 2018 (International Advisory Group for the Revision of ICD–10 Mental and Behavioural Disorders, 2011). Every mental health agency in the United States uses the DSM–5. Every mental health agency in much of the rest of the world uses the ICD–10, or a local version of the ICD–10 that has been modified for use within the respective country. DSM–5 is indeed the U.S. version of the ICD–10. The DSM–5 and ICD–10 are closely aligned and congruent nomenclatures. As one of the 194 member countries of the WHO, the United States is required to use the ICD–10 in its hospitals. The code numbers used in all clinics within the United States (and provided in DSM–5) are ICD–10 code numbers. Each WHO member country is permitted to make adjustments to the ICD to maximize its congruency with the perspective of that country ­(Frances, First, & Pincus, 1995). A country can modify the diagnostic criteria for a respective disorder as long as this modification does not result in an essentially different disorder. Any country can also decline to include a particular disorder within its version of the ICD. Finally, any country can also add

http://dx.doi.org/10.1037/0000064-003 APA Handbook of Psychopathology: Vol. 1. Psychopathology: Understanding, Assessing, and Treating Adult Mental Disorders, J. N. Butcher (Editor-in-Chief) Copyright © 2018 by the American Psychological Association. All rights reserved.

APA Handbook of Psychopathology: Psychopathology: Understanding, Assessing, and Treating Adult Mental Disorders, edited by J. N. Butcher and J. M. Hooley Copyright © 2018 American Psychological Association. All rights reserved.

41

Copyright American Psychological Association. Not for further distribution.

Widiger and Crego

a disorder to its own version of the ICD that is not included in the WHO’s ICD, as long as that country does not use a code number that is already in use in the WHO’s ICD. For example, the ninth-revision ICD code number in the fourth edition and fourth edition, text revision, of the DSM (DSM–IV and DSM–IV–TR, respectively; American Psychiatric Association, 1994, 2000) for hypochondriasis and body dysmorphic disorder was precisely the same (i.e., 300.7), yet in the United States these are considered to be very different disorders. The same code number had to be used because the ICD’s ninth revision did not recognize any distinction between these syndromes, considering body dysmorphia to be a variant of hypochondriasis (WHO, 1992). Little has changed in DSM–5. In DSM–IV, hypochondriasis and body dysmorphic disorder were at least included in the same section of the manual (for somatoform disorders). However, for DSM–5, the American Psychiatric Association shifted body dysmorphic disorder out of the somatoform section and into an obsessive-compulsive disorders section, and hypochondriasis was folded into a broader condition of illness anxiety disorder (remaining, though, within the somatic symptom disorders). Nevertheless, although again clearly different disorders, at least from the perspective of American psychiatry, their ICD–10 code numbers remain largely the same (i.e., F45.21 and F45.22, respectively), because from the perspective of the ICD–10, both continue to be variants of hypochondriasis. In fact, it has been proposed for ICD–11 that hypochondriasis (rather than body dysmorphia) leave the somatoform section to join the anxiety and obsessive-compulsive disorders (Gureje, 2015), although body dysmorphia would follow suit (remaining a variant of hypochondriasis). People have decried the impact and influence of the DSM and ICD diagnostic systems (e.g., Hyman, 2010; Lilienfeld & Treadway, 2016). Some have even suggested that clinical psychology would be better off without any official nomenclature (e.g., Markon, 2013). It is certainly the case that the diagnostic categories included within the DSM–5 do not necessarily provide the most clinically useful or valid nomenclature (Greenberg, 2013; Wakefield, 42

2016). This is in fact acknowledged explicitly within the DSM–5 itself: “It is well recognized that this set of categorical diagnoses does not fully describe the full range of mental disorders that individuals experience and present to clinicians on a daily basis” (American Psychiatric Association, 2013, p. 19). DSM–5 is not the final word. The manual has been and continues to be an ongoing work in progress (Frances et al., 1995). Nevertheless, there is considerable benefit, if not an absolute need, in having an official, authoritative nomenclature that is used by almost everyone (Blashfield, Keeley, Flanagan, & Miles, 2014; ­Kendell, 1975; Widiger, 2016; Zilboorg, 1941). This has long been recognized in the history of general medicine (Farr, 1839), as well as in psychiatry (Salmon, Copp, May, Abbot, & Cotton, 1917; Stengel, 1959). It would seem self-evident that a common nomenclature is necessary for clinical practice. Imagine the chaos if clinicians were free to use whatever classification of psychopathology they preferred. Even if they used the same diagnostic terms (which would be unlikely), they would probably use very different indicators for determining the presence of the purportedly same condition. The existence of DSM–5 and ICD–10 substantially facilitates the obtainment of reliable (and valid) diagnostic practice for clinicians and various mental health agencies. A common language is also advantageous to scientific research (Widiger, 2016). It would be quite difficult to accumulate a body of knowledge regarding psychopathology if each researcher used his or her own idiosyncratic nomenclature and his or own diagnostic criteria for a respective condition. Researchers can be highly opinionated and self-­ confident with respect to their own views regarding the nature of psychopathology. Of course, an authoritative nomenclature, such as the American Psychiatric Association’s DSM–5, might in principle hinder creativity, innovation, and progress if it stifled alternative conceptualizations (Hyman, 2010; Lilienfeld & Treadway, 2016). However, the extent to which this has ever really occurred is debatable. The American Psychiatric Association’s nomenclature has served as a useful foil, a common point of comparison, even while it has been heavily criticized. Without this consistent nexus of discussion,

Copyright American Psychological Association. Not for further distribution.

Diagnosis and Classification of Psychopathology

it would have been difficult for researchers to compare, contrast, and integrate findings with respect to alternative perspectives and proposals. Researchers have been free to assert through argument and research their own version of a diagnostic construct, and they have even asserted paradigm shifts, making the case, for example, for a shift to a dimensional model of classification (Widiger & Clark, 2000) or for a theoretically specific nomenclature (Psychodynamic Diagnostic Manual Task Force, 2006). However, given the substantial importance, authority, and impact an authoritative diagnostic manual can have, its development carries with it considerable responsibility, concern, and care. The development of the DSM–5 generated a substantial body of controversy (Decker, 2010; Frances, 2013; Greenberg, 2013; Lilienfeld & Treadway, 2016; Wakefield, 2016). A contributing factor to the magnitude of the controversies swirling around DSM–5 was the existence of the Internet and social media, the means whereby critics could quickly generate a substantial body of vocal opposition and negative publicity (Widiger & Crego, 2015). There was never a “Twitter revolution,” but the Internet was very active with agitating blogs. One of the more prominent blogs was provided by Allen Frances, chair of DSM–IV, for both Psychology Today and the Huffington Post, strongly criticizing DSM–5 proposals and announcements at nearly every turn. The authors of third edition of the DSM (DSM–III), third revised edition of the DSM (DSM–III–R), and DSM–IV were perhaps fortunate that the Internet was not yet ­available for such immediate vocal protest and opposition. The controversies besetting DSM–5, however, were not simply the result of the existence of the Internet. The controversies reflected the difficulties the authors of the DSM–5 had in handling the fundamental issues and problems that are inherent to the development of an authoritative diagnostic nomenclature. These concerns and issues will bedevil the authors of the next edition. In the sections below, we consider seven issues of central importance: (a) transparency, (b) empirical support for proposed revisions, (c) clinical utility, (d) the definition of mental disorder, (e) the impact of culture and values, (f) the shift to a dimensional model;

and (g) the shift to a neurobiological model. Each is discussed in turn. TRANSPARENCY The development of DSM–5 began with a requirement that work group and task force members sign confidentiality agreements (Greenberg, 2013; Wakefield, 2016). No such requirement had been imposed on the authors of DSM–IV or any prior edition, nor is it entirely clear why there should be any constraint on work group members sharing their experiences, views, observations, and opinions with persons outside of the official process. The stated purpose of the confidentiality contracts was in part “to prevent the premature dissemination of internal deliberations about final decisions” (American Psychiatric Association, 2012a); they were “not intended to prohibit timely discussion or public dissemination” (American Psychiatric ­Association, 2012a). It is understandable for a work group not to want to have preliminary ideas disseminated prematurely. Work group members will float ideas that might be outrageously flawed and rejected fairly quickly. Their dissemination in the early stages of a work group effort might be inaccurately interpreted as serious proposals that have a strong possibility of receiving final approval, thereby generating unnecessary drama and controversy. Nevertheless, any effort to restrain the dissemination of work group deliberations comes at the cost of conveying an impression of secrecy, concealment, and censorship. The distinction between a premature and a timely dissemination of proposed revisions is not at all clear, and the inclusion of a confidentiality clause does not convey a spirit of free and open expression of ideas and opinions. The authors of DSM–5 boldly stated that “the process for developing DSM–V has been the most open and inclusive ever” (Schatzberg, Scully, Kupfer, & Regier, 2009, p. 1; early articles on DSM–5 often used Roman numerals rather than Arabic). Yet never in the development of any previous edition of the diagnostic manual had work group and task force members been required to sign confidentiality contracts to prevent the dissemination of work group discussion and deliberation. 43

Copyright American Psychological Association. Not for further distribution.

Widiger and Crego

Significant concerns with respect to the process with which DSM–5 was being constructed were perhaps first raised by Robert Spitzer, chair of DSM–III and DSM–III–R. He had been denied minutes of DSM–5 Work Group meetings and registered a formal complaint with the DSM–5 Task Force (Greenberg, 2013). Drs. Frances and Spitzer (chairs of DSM–IV and DSM–III, respectively) eventually submitted a joint letter to the Board of Trustees of the American Psychiatric Association on July 7, 2009, expressing concerns with respect to the process with which DSM–5 was being constructed, including the confidentiality agreements (Greenberg, 2013). The letter by Frances and Spitzer was initiated by the fact that the field trial for DSM–5 was about to begin before the proposals had received any critical review or even been revealed. Frances followed this joint letter with additional letters of his own and a series of articles and blogs, which eventually led to the decision of the DSM–5 Task Force to postpone the field trial until after all of the proposals had been posted on a website in February 2010, thereby allowing for public awareness and external review (Decker, 2010). The website posting resulted in a considerable amount of objection and opposition to many of the proposals, perhaps vindicating the concerns raised by Spitzer and Frances. EMPIRICAL SUPPORT All of the mental disorder diagnoses in DSM–5 have some degree of empirical support (Frances et al., 1995). It would be far from accurate or fair to suggest that the conditions included therein are illusory constructs with no empirical support (Lilienfeld & Treadway, 2016). A fundamental difficulty for the authors of a diagnostic manual, however, is that there is no objective, independent laboratory assay to document the existence of a mental disorder (Kapur, Phillips, & Insel, 2012). The decision to consider a condition or behavior pattern a mental disorder is a matter of opinion (Frances & Widiger, 2012), supported by research that is presumably sufficiently compelling (Kendler, 1990; Meehl, 1986). One infers the presence of a mental disorder on the basis of impairment, dysfunction, distress, pathology, or dyscontrol (Spitzer & Williams, 1982; 44

Widiger & Sankis, 2000), but there is a wide array of behavior patterns that are associated with these indicators. There have been influential guidelines for what should be required for the validation of a mental disorder diagnosis, such as discriminant validity (delimitation from other disorders), family history (heritability), antecedents, risk factors, course, biological markers, follow-up (outcome), and treatment implications (e.g., Kendler, 1990; Robins & Guze, 1970). However, these guidelines are themselves opinions, and even if everyone agreed to use a particular set of guidelines, there would be no objective or consensus algorithm for how to consider the findings with respect to these guidelines (i.e., whether there is indeed sufficient empirical support). As in the case of any construct validation (Strauss & Smith, 2009), empirical research must be interpreted, and there will be differences of opinion as to the correct interpretation. There is research to support the validity of such diagnostic constructs as hypersexual disorder (Kafka, 2010) and depressive personality disorder (Bagby, Watson, & Ryder, 2012). There is a good deal of research to support considering bereavement to be a mental disorder (Kendler, 2010; Zisook, Shear, & Kendler, 2007). At what point, though, this empirical support becomes sufficiently compelling to include in the diagnostic manual is never certain and may always be debatable (Widiger & Mullins-Sweatt, 2008). Reasonable persons will disagree as to whether there is in fact sufficient empirical support, and unreasonable persons can and will disagree vehemently. It is in this context that proposals for a new diagnosis are generated, and it is then not terribly surprising that there will be disagreement, at times contentious. What constitutes a mental disorder is not a trivial decision because it can have quite an important impact on significant social and political issues (e.g., see Bayer & Spitzer, 1982, for a discussion of the controversy surrounding the inclusion of homosexuality in previous editions of the diagnostic manual). For example, proposed for DSM–5 was a revision to the criterion set for autism disorder that arguably increased the threshold for diagnosis, leaving many persons diagnosed with DSM–IV Asperger’s disorder

Copyright American Psychological Association. Not for further distribution.

Diagnosis and Classification of Psychopathology

no longer qualifying for the special benefits, services, and support that had been available to them before DSM–5 (Volkmar & McPartland, 2014). The authors of DSM–5 therefore made an essentially sociopolitical decision to allow persons who had been diagnosed with autism using DSM–IV to continue to receive the diagnosis (American Psychiatric Association, 2013, p. 51), even though they had concluded that the DSM–IV threshold was wrong. At some point, this grandfather clause will expire, but presumably, the parents of the children who no longer qualify for special services will not protest in large part because they had never experienced the benefits of receiving the DSM–IV diagnosis. In DSM–IV, major depressive disorder was not diagnosed in response to the loss of a loved one. The authors of DSM–5, however, proposed to eliminate the bereavement exclusion criterion for major depressive disorder because they did not consider it to be valid (Kendler, 2010). The rationale for this decision is discussed later in this chapter. Facing substantial public opposition because of the implication that grieving for the death of one’s loved one would now be considered a mental illness (Wakefield, 2011, 2016), the DSM–5 Task Force again decided to leave the decision largely up to the clinician, who can choose to consider it to be a mental disorder or not (American Psychiatric Association, 2013, pp. 125–126). In sum, in the absence of a gold standard or perhaps even confidence regarding the decision, the authors of DSM–5 allowed clinicians to simply decide for themselves for two proposals that were particularly controversial or sociopolitically heated. The chair and vice-chair of DSM–5 (i.e., Drs. Kupfer and Regier) stated that the development of DSM–5 followed the procedure used for DSM–IV, including literature reviews, data reanalyses, and field trials (Regier, Narrow, Kuhl, & Kupfer, 2009). Frances, Widiger, and Pincus (1989) had suggested that “the major innovation of DSM–IV [was not] having surprising new content but rather will reside in the systematic and explicit method by which DSM–IV will be constructed and documented” (p. 375). Frances (2013) felt that the authors of DSM–5 flipped this priority on its head, with emphasis being given to new content and inadequate

attention given to first conducting systematic, thorough, and balanced reviews. Kendler, Kupfer, Narrow, Phillips, and Fawcett (2009) did develop explicit guidelines for proposed revisions to and inclusion of new diagnoses in DSM–5. These guidelines indicated that any change to the diagnostic manual should be accompanied by “a discussion of possible unintended negative effects of this proposed change, if it is made, and a consideration of arguments against making this change should also be included” (p. 2). Kendler et al. further stated that “the larger and more significant the change, the stronger should be the required level of support” (p. 2). This was a very commendable and demanding set of guidelines, but it did not appear that work group members were actually required to adhere to them (Frances & Widiger, 2012; Wakefield, 2016; Widiger & Crego, 2015). Adherence to the guidelines would seem to be required by the presence of the DSM–5 Scientific Review Committee, whose purpose was to review the adequacy of empirical support for every proposal (Kendler, 2013). The chair of this committee was the lead author of the guidelines for revision (i.e., Kendler et al., 2009). The initial literature reviews that provided the empirical support for DSM–5 proposals were first posted on the DSM–5 website in February 2010. Revisions to these literature reviews continued to be posted through 2012. Most are no longer available (Wakefield, 2016), although there are search engines that can retrieve documents that have been removed from websites (Widiger & Crego, 2015). Many of the DSM–5 literature reviews did appear to meet the spirit of the Kendler et al. (2009) guidelines, such as the reviews for hypersexual disorder (Kafka, 2010), dissociative disorders (Spiegel et al., 2013), and a callous–unemotional specifier for conduct disorder (Frick, Ray, Thornton, & Kahn, 2014). However, others did not.

Behavioral Addiction The authors of DSM–5 created a new class of behavioral addiction disorders, subsuming substance use disorders and pathological gambling. The literature review that provided the rationale and empirical support for this major revision consisted of just two sentences: “Pathological 45

Copyright American Psychological Association. Not for further distribution.

Widiger and Crego

(disordered) gambling has commonalities in clinical expression, etiology, comorbidity, physiology and treatment with Substance Use Disorders. These commonalities are addressed in the following selected papers from a relatively large literature” (American Psychiatric Association, 2010c). There was no discussion of the potential costs or risks of developing a new diagnosis of behavioral addiction that could expand the manual to include such debatable conditions as Internet addiction and shopping addiction (Petry, 2006). It is readily conceivable that a thorough and compelling literature review could have been generated that would have supported the proposal (e.g., Shaffer, LaPlante, & Nelson, 2012), but none was posted on the DSM–5 website. The proposed revision was approved despite the absence of a credible review.

Somatic Symptom Disorder One of the significant changes made in DSM–5 was to collapse the diagnoses of hypochondriasis, pain disorder, and somatization disorder into one common disorder, titled somatic symptom disorder (American Psychiatric Association, 2013; see also Chapter 22, this volume), despite quite a bit of research documenting important differences between them (Bouman & Eifert, 2009). The literature review in support of the DSM–5 proposal indicated that “the proposal is to group together these heretofore separately recognized disorders because in fact, there are 3 diverse sources suggesting considerable overlap among them” (American Psychiatric Association, 2010b). One of the three sources was an unpublished survey of physicians, 52% of whom felt there was a lot of overlap. This is barely a majority, nor is it at all clear what a physician’s subjective impression of “a lot of overlap” really means. Does the impression of a lot of overlap mean considerable overlap, or enough overlap to indicate that the distinctions between them should be removed? The second source was the rate of actual diagnostic co-occurrence in clinical settings, but it was acknowledged that there was in fact only “limited data regarding overlap,” consisting of just three studies. The first study indicated a problematic overlap that concerned the DSM–III–R criteria for hypochondriasis (i.e., Barsky, Wyshak, & Klerman, 46

1992). The second study addressed the findings of the first study and concluded that they had in fact “identified a distinct hypochondriasis symptom cluster” (Fink et al., 2004, p. 161). The third study with regard to overlap reported that 20% of persons with somatization disorder also had hypochondriasis (Escobar et al., 1998), which is hardly a problematic overlap. Finally, the last source for the “considerable overlap” was similarities in the treatment for hypochondriasis, pain disorder, and somatization disorder, which simply meant they all involved the use of cognitive–behavioral therapy (CBT), antidepressants, or both, a commonality that is evident across many other mental disorders. In sum, the authors of this proposal acknowledged that it was a major change (American Psychiatric Association, 2010b) to collapse the three diagnoses into one condition, but the research they cited in support of it was sorely limited in actually demonstrating the existence of even a degree of problematic overlap of hypochondriasis, pain disorder, and somatization disorder, let alone considerable overlap. Nevertheless, this proposal was approved.

Mood Dysregulation Disorder The literature review for a new diagnosis, mood dysregulation disorder (initially titled temper dysregulation disorder of childhood), was thorough in its coverage, but it acknowledged that the empirical support for the proposal was, at best, severely limited, if not explicitly inadequate. The impetus for this proposal was the increasing number of children with temper tantrums who were being diagnosed with bipolar mood disorder, and provided with medications, in the absence of adequate scientific support for the validity of this diagnosis in children (Fawcett, 2010). It was felt that the excessive diagnosis of bipolar mood disorder in children might be addressed through the development of specific and explicit diagnostic criteria that would be sufficiently restrictive. Of course, the existence of the diagnosis within DSM–5 will likely have the opposite effect of increasing the medication of children with temper tantrums by providing the diagnosis with substantial credibility and perceived validity that is perhaps undeserved (Frances & Widiger, 2012; Hyman, 2010).

Copyright American Psychological Association. Not for further distribution.

Diagnosis and Classification of Psychopathology

The Childhood and Adolescent Disorders Work Group (2010) acknowledged that the research “has been done predominately by one research group in a select research setting, and many questions remain unanswered” (p. 4). This point was reiterated within a joint statement by the Mood Disorders and Childhood and Adolescent Disorders Work Group (2010) that “both work groups are concerned by the fact that the work on severe mood dysregulation [in children] has been done predominately by one research group in a select research setting” (p. 6). Yet Kendler et al. (2009) had stated explicitly within the guidelines for DSM–5 that a new diagnosis “should rarely if ever be based solely on reports from a single researcher or research team” (p. 5). Instead, the authors of the proposal indicated that its inclusion in DSM–5 was actually needed to generate the research that would eventually (or hopefully) support its validation. Indeed, it can be argued that one of the major “take-home” messages from the controversy about the diagnosis of pediatric bipolar disorder is the fact that the research needs of a large population of children with severe irritability are not being met, particularly with respect to clinical trials. (Mood Disorders and Childhood and Adolescent Disorders Work Group, 2010, p. 8) As expressed by the Childhood and Adolescent Disorders Work Group (2010), the inclusion of this new diagnosis will help to “‘jump-start’ research on severe irritability in youth” (p. 9). In other words, not only was there an acknowledgment of inadequate research to justify its inclusion, but the proposal was being made to help generate the research that might eventually support its validity. This would appear to be explicitly inconsistent with the guidelines of Kendler et al. (2009). Nonetheless, the proposal was approved.

Cyclothymia One of the more unusual revisions for DSM–5 concerned the diagnosis of cyclothymia. In DSM–III (American Psychiatric Association, 1980) and DSM–III–R (American Psychiatric Association,

1987), diagnosis of cyclothymia required that the symptoms of hypomania meet the diagnostic threshold for a hypomanic episode. This was loosened somewhat in DSM–IV, wherein it was only required that there be “numerous periods with hypomanic symptoms” (American Psychiatric Association, 1994, p. 365), albeit most cases would certainly be above threshold for a hypomanic episode. However, DSM–5 (American Psychiatric Association, 2013) requires that the “hypomanic symptoms . . . do not [emphasis added] meet criteria for a hypomanic episode” (p. 139). This is a significant change, and one that is difficult to understand. What would be the rationale for requiring that the hypomanic symptoms be below threshold for a hypomanic episode? In DSM–5, persons who have hypomanic episodes (along with dysthymic episodes) are no longer being given the diagnosis of cyclothymia; the diagnosis is reserved for persons who fail to have hypomanic episodes (the diagnosis for persons who have hypomanic and dysthymic episodes is not clear). It is difficult to understand the rationale for this revision, and it is even more difficult to find the rationale. It was initially stated on the DSM–5 website that there were no proposed revisions for the diagnosis of cyclothymia (American Psychiatric Association, 2010a). In the final posting on the website, the rationale for the revision simply stated, “The DSM–5 diagnostic criteria for this disorder are similar to those in DSM–IV, with very minor wording changes being proposed” (American Psychiatric Association, 2012b). Requiring that the symptoms of hypomania be below threshold for an actual episode of hypomania does not appear to be simply a minor change in wording. It is a very substantial change to the diagnosis, comparable to changing the criteria for bipolar mood disorder to require that the manic symptoms be below rather than above the threshold for a manic episode. That would certainly not be a minor change in wording. In the section of DSM–5 highlighting changes from DSM–IV to DSM–5 (American Psychiatric Association, 2013, pp. 809–816), there is again no mention of any change for cyclothymia. In an extensive summary of the rationale for changes being made to the bipolar mood disorders (including cyclothymia) coauthored by the chair of DSM–5 as well as work group 47

Widiger and Crego

members in charge of cyclothymia, there is again no reference to the proposal to shift the cyclothymic diagnosis to below threshold for a hypomanic episode (i.e., Kupfer et al., 2011). In sum, no literature review was ever provided to justify this odd change, nor was there even an explanation for its rationale. This would again appear to be quite inconsistent with the guidelines of Kendler et al. (2009).

Copyright American Psychological Association. Not for further distribution.

DSM–5 Field Trials The field trials for DSM–5 were also very different from those for DSM–IV (First, 2016). The purpose of the field trials for DSM–IV was to empirically test the validity of proposed revisions, compare alternative proposals, and assess their potential impact (Widiger, Frances, Pincus, Davis, & First, 1991). This was not the intention of the DSM–5 field trials, which were confined largely to questions of feasibility, reliability, and face validity (Clarke et al., 2013). “The main interest was to determine the degree to which two clinicians would agree on the same diagnosis” (Clarke et al., 2013, p. 44). This question is interesting, but it has already been well established that psychiatric diagnoses tend to be unreliable in the absence of systematic clinical assessments (Garb, 2005; Garb, Lilienfeld, & Fowler, 2016; Spitzer, Endicott, & Robins, 1975; Spitzer & Fleiss, 1974). More important, it is not clear how answering this question would be relevant to a decision of whether to implement a particular proposal (First, 2016). Of more importance for a field trial concerned with proposed revisions is to address questions of validity (Kendler, 1990); to compare alternative proposals to one another, including a comparison to the existing nomenclature (Widiger et al., 1991); and to address the potential costs and concerns specific to each proposal (Frances & Widiger, 2012; Kendler et al., 2009). The DSM–5 field trials largely ignored what probably should have been their primary concerns (First, 2016). In fact, the field trials were unable to obtain any information for some of the proposals that were intended to be researched (e.g., attenuated psychosis syndrome, bipolar II, hoarding, mild neurocognitive disorder, narcissistic personality disorder, and schizotypal personality disorder) because the sites did not have a sufficient number of cases (Clarke et al., 2013; Regier et al., 2013). It 48

is unclear why sites were chosen if they would not have enough cases over the course of the data collection (Jones, 2012). CLINICAL UTILITY Authors of a diagnostic manual are charged with addressing both construct validity and clinical utility (Kendell & Jablensky, 2003). Construct validity is concerned with determining truthfulness or verisimilitude—whether the findings obtained for the construct are consistent with its theoretical conceptualization (Strauss & Smith, 2009). “Clinical utility is the extent to which DSM assists clinical decision makers in fulfilling the various clinical functions of a psychiatric classification” (First et al., 2004, p. 947). Clinical utility essentially concerns facility of usage, communication with colleagues and patients, and treatment planning (First, 2010; Mullins-Sweatt, Lengel, & DeShong, 2016; Reed, 2010). A diagnosis can have well-established validity but be of little use to a clinician or even be problematic in clinical practice (Mullins-Sweatt et al., 2016). The authors of the diagnostic manual have always asserted that clinical utility has been a primary concern, if not the primary concern. The chief architects of DSM–IV stated, “There is unanimous agreement, even among those engaged in research, that the primary purpose of DSM–IV is to facilitate clinical practice and communication” (Frances et al., 1991, p. 410). This emphasis was again stated quite forcefully in the first paragraph of the introduction to this diagnostic manual: “Our highest priority has been to provide a helpful guide to clinical practice” (American Psychiatric Association, 2000, p. xxiii). More recently, this point was reiterated in DSM–5: “All of [our] efforts were directed toward the goal of enhancing the clinical usefulness of DSM–5” (American Psychiatric Association, 2013, p. 5). It can be difficult, however, to even notice much attention actually being given to clinical utility, at least in the construction of the DSM–III through DSM–5. A concern for DSM–III and each edition thereafter has been that these manuals were developed by researchers, reflecting largely their interests and usage, with little attention being given to the concerns of clinicians (First et al.,

Copyright American Psychological Association. Not for further distribution.

Diagnosis and Classification of Psychopathology

2004; Mullins-Sweatt & Widiger, 2009). One of the stated goals for DSM–III–R was “suitability for describing subjects in research studies” (American Psychiatric Association, 1987, p. xx), whereas suitability for describing patients in clinical practice was not acknowledged (Mullins-Sweatt et al., 2016). Indeed, the diagnostic criterion sets of DSM–III and DSM–III–R were often quite unrealistic for use within clinical practice (Frances et al., 1989). DSM–III–R generalized anxiety disorder included 22 diagnostic criteria; somatization disorder had 35. Researchers have the time (and at times the funding) to conduct assessments that last for hours, but clinicians do not. One of the mandates for DSM–IV was to improve ease of usage (Frances et al., 1989). The more egregious criterion sets of DSM–III–R were indeed reduced in length (e.g., antisocial personality disorder, conduct disorder, and somatization disorder), but it remains questionable whether the specific and explicit criterion sets that are so very useful in research are at all realistic in clinical practice (First, 2010; Reed, 2010). A common criticism of clinicians is that they do not adhere to the diagnostic manual’s criterion sets (Garb, 2005). However, in many cases this adherence would be impractical, if not impossible. For instance, it would take approximately 2 hours for a clinician to systematically assess for each of the DSM–5 personality disorder diagnostic criteria (Widiger & Samuel, 2005). It is perhaps then hardly surprising that clinicians routinely fail to be systematic or comprehensive in their assessments (e.g., Morey & Benson, 2016). One suggestion to address this problem has been to present the specific and explicit criterion sets in a descending order of diagnostic value (MullinsSweatt & Widiger, 2009). Not all of the diagnostic criteria need to be assessed, and some diagnostic criteria are considerably more informative than others (Widiger, Hurt, Frances, Clarkin, & Gilmore, 1984). If clinicians do not in fact have the time or means to consider all of the diagnostic criteria, the authors of the criterions sets could at least provide them with empirically validated information as to which diagnostic criteria are most informative. This proposal was considered for the personality disorders section of DSM–IV but only partially

implemented (Mullins-Sweatt & Widiger, 2009). Of course, even if it was provided, clinicians may not in fact adhere to the descending order, having their own preferred diagnostic criteria (Garb, 2005). Matters of clinical utility have been a more explicit concern for the ICD (International Advisory Group for the Revision of ICD–10, 2011). Perhaps the primary distinction between DSM–IV and ICD–10 has been that the latter has two versions, one for clinicians (the ICD–10—Clinical Modification) and the other for researchers (the ICD–10 Classification of Mental and Behavioural Disorders: Clinical Descriptions and Diagnostic Guidelines; WHO, 1992). The research version includes specific and explicit criterion sets, albeit most international researchers use the DSM–IV (American Psychiatric Association, 1994) and now the DSM–5 (American Psychiatric Association, 2013) rather than the research version of ICD–10 (WHO, 1992). The clinician version of the ICD uses narrative paragraph descriptions because clinicians find specific and explicit criterion sets to be too complex and cumbersome (Reed, 2010). Narrative paragraphs are considerably easier to use because there is no requirement to assess for the presence of individual features. The clinician can provide a rather quick diagnostic impression (Westen, Shedler, & Bradley, 2006). The provision of different versions for researchers and clinicians was considered for DSM–IV. The proposal was not implemented because it implied that clinicians were free to provide less reliable diagnoses than researchers (which would appear to be antithetical to optimal clinical practice). It would also hinder the ability to transfer information obtained from research to clinical treatment (Frances et al., 1995). One of the initial proposals for the DSM–5 personality disorders was to replace the specific and explicit criterion sets with narrative paragraphs (Skodol, 2012). This proposal was withdrawn, however, because of concerns that it would sacrifice reliability (and validity) for the sake of ease of usage (Widiger, 2011; Zimmerman, 2011). No explicit guidelines are provided within the narrative paragraphs as to which of the features should be emphasized, or even considered (Spitzer, Williams, & Skodol, 1980). Clinicians are likely to vary widely in 49

Copyright American Psychological Association. Not for further distribution.

Widiger and Crego

how they interpret and apply the narrative descriptions, as happened with the second edition of the DSM (DSM–II; Spitzer & Fleiss, 1974). Reliability would likely be even worse than it was for DSM–II given the considerable length and complexity of the proposed DSM–5 narratives (Widiger, 2011). ICD–11 is likely to shift closer to the specific and explicit criterion sets of DSM–5. The major innovation of DSM–III (American Psychiatric Association, 1980) was the inclusion of specific and explicit criteria (Spitzer et al., 1980). Before DSM–III, mental disorder diagnosis was notoriously unreliable (Spitzer et al., 1975; Spitzer & Fleiss, 1974). Research has since indicated that mental disorders can be diagnosed reliably if the researchers do in fact adhere to a common, uniform criterion set, thereby yielding consistent and valid information regarding etiology, pathology, course, and treatment (Kendler, Muñoz, & Murphy, 2010). Proposed for ICD–11 is to replace the narrative paragraphs with lists of “essential features.” For instance, for schizophrenia there would be a requirement of two of seven specified features (First, Reed, Hyman, & Saxena, 2015). Nevertheless, the authors of ICD–11 suggest that their criterion sets will not be as specific or exacting as those of DSM–5. “While these lists of essential features superficially resemble diagnostic criteria . . . for the most part they lack the specific and arbitrary duration thresholds and ‘pick lists’ of items that characterize the diagnostic criteria sets in DSM–5” (First et al., 2015, p. 85). The intention is for the wording to be relatively looser than is the case in DSM–5, and in some instances there will be no specification as to how many of the features are required, allowing for a more “flexible exercise of clinical judgment” (First et al., 2015, p. 85). DEFINITION OF MENTAL DISORDER The boundaries of the diagnostic manual increase with each new edition (Blashfield et al., 2014), and there has long been concern that this expansion encroaches on normal problems of living (Follette & Houts, 1996; Frances, 2013; Horwitz & Wakefield, 2007; Wakefield, 2016). Coverage has again increased with DSM–5, with such new diagnoses as 50

disruptive mood dysregulation disorder, excoriation disorder, hoarding disorder, illness anxiety disorder, premenstrual dysphoric disorder, and binge eating disorder, as well as the expansion of substance use disorder to include behavioral addictions, the addition of a muscle dysmorphia subtype to body dysmorphic disorder, a lowered threshold for a paraphilia, and the removal of the bereavement exclusion criterion from the diagnosis of a major depressive disorder. An explicit definition of what constitutes a mental disorder would presumably provide a useful guide as to what to include within a diagnostic manual. DSM–III was the first edition to include an explicit definition, the result of an effort to develop explicit criteria for deciding whether a behavior pattern (homosexuality in particular) should be classified as a mental disorder (Spitzer & Williams, 1982). However, the definition of mental disorder has not been particularly effective in resolving debates as to what to include within the manual (Wakefield & First, 2013). Two illustrative examples of the debatable boundaries between normality and abnormality are provided by the diagnosis of pedophilia and the bereavement exclusion criterion for major depressive disorder.

Pedophilia In DSM–III–R (American Psychiatric Association, 1987), the diagnosis of pedophilia required only that an adult have recurrent intense urges and fantasies involving sexual activity with a prepubescent child that lasted over a period of at least 6 months and have acted on them (or be markedly distressed by them). However, every adult who engaged in a sexual activity with a child for longer than 6 months would then meet these diagnostic criteria. The authors of DSM–IV were concerned that DSM–III–R was not providing adequate guidance for determining when persistent deviant sexual behavior is the result of a mental disorder versus when it is a willful criminal act. Presumably, some persons who are repeatedly engaging in sexual activities with a prepubescent child are not being compelled to do so by the presence of psychopathology. Some persons are doing this on a willful, voluntary basis. The authors of DSM–IV, therefore, added the requirement that

Copyright American Psychological Association. Not for further distribution.

Diagnosis and Classification of Psychopathology

“the behavior, sexual urges, or fantasies cause clinically significant distress or impairment in social, occupational, or other important areas of functioning” (American Psychiatric Association, 1994, p. 523). This might not be an adequate basis on which to distinguish between willful, voluntary ­versus pathological sexual deviance, but it was at least an attempt to make a distinction. Spitzer and Wakefield (1999), however, argued that the DSM–IV impairment criteria were sorely problematic. They concurred with a concern raised by the National Law Center for Children and Families that DSM–IV might have contributed to the appearance of a normalization of pedophilic behavior by allowing the diagnoses not to be applied if the persons who have engaged in these acts were not experiencing any impairment to themselves. They felt that if the behavior was not considered to be a mental disorder, this might suggest that it was normal or perhaps even acceptable to engage in these acts. Frances et al. (1995) had argued that pedophilic sexual “behaviors are inherently problematic because they involve a nonconsenting person (in the case of exhibitionism, voyeurism, or frotteurism) or a child (pedophilia) and may lead to arrest and incarceration” (p. 319). Therefore, any person who engaged in an illegal sexual act (for longer than 6 months) would be exhibiting a clinically significant social impairment and would therefore meet the DSM–IV threshold for diagnosis. However, one should not use the illegality (or immorality) of an act to help determine when an act is a disorder (Spitzer & Williams, 1982). This would confuse a legal (and moral) decision with a clinical decision, suggesting that if the behavior is illegal, immoral, it is then also pathological, making no distinction between a willful sexual deviance and a pathological sexual deviance. Indeed, the DSM–IV definition (and now the DSM–5 definition) indicated explicitly that neither deviance nor conflicts with the law are sufficient to warrant a diagnosis (American Psychiatric Association, 1994, 2013). The diagnostic criteria for pedophilia were revised in DSM–IV–TR to return to what was provided in DSM–III–R in order to try to avoid the misunderstanding that an absence of impairment would suggest that the behavior is considered to be normal (First & Pincus, 2002). However, the DSM–IV–TR

criteria allowed simply the presence of the behavior for longer than 6 months to qualify for the presence of the disorder, thereby again providing no meaningful distinction between deviant behavior that is willful and volitional from pedophilic behavior that is driven by some form of underlying pathology. The threshold for a paraphilic disorder has been further lowered in DSM–5. The diagnosis can now be given if the behavior is harmful only to others (American Psychiatric Association, 2013). Willful, voluntary behavior that is not driven by an underlying psychopathology constitutes a mental disorder if that behavior is harmful to someone else. This is perhaps comparable to stating that all cases of theft would constitute the disorder of kleptomania because thefts are harmful to others. In fact, actual harm to others is not even required. Simply risk of harm to others is sufficient for the diagnosis (American Psychiatric Association, 2013, p. 685).

Bereavement The DSM–IV criterion set for major depressive disorder excluded most instances of depressive reactions to the loss of a loved one (referred to as an uncomplicated bereavement). It is generally considered normal to be significantly depressed after the loss of a loved one. Wakefield (2011) noted, though, that it was logically inconsistent to allow the diagnosis of major depression in response to the loss of physical health, job, or employment while excluding the diagnosis if the loss was a loved one. It was a mental disorder if one became depressed in response to the prospect of losing one’s own life to a terminal illness, but not if the depression was in response to the death of a close relative. The DSM–5 Mood Disorders Work Group agreed with Wakefield (2011) with regard to the existence of this logical inconsistency. Depression in response to the loss of a loved one does not appear to be meaningfully different from depression in response to other important losses (Kendler, 2010). However, rather than add exclusion criteria for the other losses, as Wakefield suggested, the work group deleted the exclusion criterion for bereavement (Zisook et al., 2009). This decision, albeit controversial, may, though, have a compelling rationale. What is currently 51

Copyright American Psychological Association. Not for further distribution.

Widiger and Crego

considered to be a normal depression in response to the loss of a loved one does include pain, suffering, and meaningful impairments in functioning, and it is often outside the ability of the bereaved person to fully control. It is reasonable and understandable to respond to the loss of a son or daughter (i.e., a psychological trauma) with depression, but many physical disorders and injuries are themselves reasonable and understandable responses to a physical trauma (e.g., impairment secondary to the experience of a car accident). The loss is perhaps best understood as simply part of the etiology for the disorder. “Responses to a significant loss (e.g., bereavement, financial ruin, losses from a natural disaster, a serious medical illness or disability)” (American Psychiatric Association, 2013, p. 161) can now all be diagnosed as a mental disorder. However, the authors of DSM–5 neglected to also revise the definition of mental disorder to be consistent with this revision to the diagnostic criteria for a major depressive disorder because the manual continues to state that “an expectable or culturally approved response to a common stressor or loss, such as the death of a loved one, is not a mental disorder” (American Psychiatric Association, 2013, p. 20).

Alternative Definitions of Mental Disorder Wakefield (1992) developed a “harmful dysfunction” definition of mental disorder wherein dysfunction is a failure of an internal mechanism to perform a naturally selected function (e.g., inability to experience guilt) and harm is a value judgment that the design failure is harmful to the individual (e.g., imprisonment, loss of employment, and eventual impoverishment resulting from failure to learn from repeated arrests). Wakefield’s definition received substantial attention and was considered for inclusion in DSM–5 (Rounsaville et al., 2002). However, Wakefield’s definition has also received quite a bit of critical review (e.g., Bergner, 1997; Kirmayer & Young, 1999; Lilienfeld & Marino, 1999; W ­ idiger & Sankis, 2000). One concern is its reliance on evolutionary theory, thereby limiting its relevance and usefulness to alternative models of etiology and pathology (Bergner, 1997). Wakefield’s definition might even be inconsistent with some sociobiological (evolutionary) models of psychopathology. 52

Cultural evolution may at times outstrip the pace of biological evolution, rendering some designed functions that were originally adaptive in earlier time periods maladaptive in many current environments (Lilienfeld & Marino, 1999; Widiger & Sankis, 2000). For example, “the existence in humans of a preparedness mechanism for developing a fear of snakes may be a relic not well designed to deal with urban living” (Buss, Haselton, Shackelford, Bleske, & Wakefield, 1998, p. 538). In this instance, the internal mechanism (i.e., fear response) is performing a naturally selected function consistent with evolution, but that is precisely why it is a dysfunctional disorder. In addition, missing from Wakefield’s (1992) definition of mental disorder, as well as from the definition included in DSM–5, is any reference to dyscontrol. Mental disorders are perhaps best understood as dyscontrolled impairments in psychological functioning (Kirmayer & Young, 1999; Klein, 1999; Widiger & Sankis, 2000). “Involuntary impairment remains the key inference” (Klein, 1999, p. 424). Dyscontrol is one of the fundamental features of mental disorder emphasized in Bergner’s (1997) “significant restriction” and Widiger and Sankis’s (2000) “dyscontrolled maladaptivity” definitions of mental disorder. Fundamental to the concept of a mental disorder is perhaps the presence of impairments secondary to feelings, thoughts, or behaviors over which a normal (healthy) person has adequate self-control to alter or adjust to curtail the impairments, if he or she wishes to do so (Widiger & Sankis, 2000). To the extent that a person willfully, intentionally, freely, or voluntarily engages in harmful sexual acts, drug usage, gambling, or child abuse, the person would not be considered to have a mental disorder. People seek professional intervention in large part to obtain the insights, techniques, skills, or other tools (e.g., medications) that would increase their ability to better control their mood, thoughts, or behavior. Dyscontrol as a component of mental disorder does not imply that a normal person has free will, a concept that is, at best, difficult to scientifically or empirically verify. A person with a mental disorder is analogous to a computer lacking the necessary software to combat particular viruses or execute

Copyright American Psychological Association. Not for further distribution.

Diagnosis and Classification of Psychopathology

effective programs. Pharmacotherapy alters the neural connections of the central nervous system (the hardware), whereas psychotherapy alters the cognitions (the software) in a manner that increases a person’s behavioral repertoire, allowing the person to respond more effectively to stressors, threats, and losses. A computer provided with new software has not been provided with free will, but it has been provided with more options to respond more effectively to an intrusive viral threat. A definition of mental disorder consisting of dyscontrol and maladaptivity would likely encourage further expansion of the diagnostic manual, which has already received considerable objection (e.g., Follette & Houts, 1996; Frances, 2013; Kirk, 2005; Wakefield, 2016). Alternatively, however, perhaps the suggestion that the manual should not be expanding should itself be questioned. It is to be expected that scientific research and increased knowledge will lead to the recognition of more instances of psychopathology (Wakefield, 1998, 2001). In addition, an assumption that only a minority of the population currently has, or will ever have, a mental disorder (e.g., Regier & Narrow, 2002) is perhaps remarkably unrealistic. Very few people fail to have at least some physical disorders, and all people suffer from quite a few physical disorders throughout their lifetime. It is unclear why it should be substantially different for mental disorders, as though most persons have been fortunate to have obtained no problematic genetic dispositions or vulnerabilities and have never experienced significant economic, environmental, or interpersonal stress, pressure, or conflict that would tax or strain psychological functioning. Optimal psychological functioning, like optimal physical functioning, might be an ideal that is achieved by only a small minority of the population. The rejection of a high prevalence rate of psychopathology may reflect the best of intentions, such as concerns regarding stigmatization (Kirk, 2005) or the potential impact on funding for treatment (Regier & Narrow, 2002). However, these social and political concerns might be hindering a more dispassionate and accurate recognition of the true rate of psychopathology within the general population (Widiger & Sankis, 2000).

CULTURE AND VALUES A fundamental concern for a diagnostic system is whether it is universal, that is, valid and acceptable across alternative cultural belief systems (see Chapter 6, this volume). There is both a “strong” and a “weak” cross-cultural critique of current scientific understanding of psychopathology, perhaps better understood as a distinction between fundamental, fatal flaws versus local limitations. The weak critique does not question the validity of the concept of mental disorder but does argue that local social and cultural processes affect and potentially bias the science and practice of diagnosis to the extent that the researcher’s or clinician’s local cultural background clouds his or her objectivity (López & Guarnaccia, 2016). These concerns are not weak in the sense that they are trivial or inconsequential, but they do not dispute the fundamental validity of the concept of mental disorder or the science of psychopathology. The strong or fundamental critique, in contrast, is that the construct of mental disorder is itself a ­culture-bound, socially constructed belief that reflects the biases of Western society and that the science of psychopathology is valid only in the sense that it is an accepted belief system of a particular culture (Maddux, Gosselin, & Winstead, 2016). The concept of mental disorder does include a value judgment that there should be necessary, adequate, or optimal psychological functioning (Wakefield, 1992). However, this acknowledgment can be misunderstood as an admission of strong critique or a fatal flaw, as though the concept of a mental disorder is itself simply a subjective value judgment of a local culture. That is not what is meant by this value judgment. The same value judgment is also inherent in the concept of a physical disorder (Widiger, 2002, 2016). In a world in which there were no impairments or threats to physical functioning, the construct of a physical disorder would have no meaning except as an interesting thought experiment. Meaningful and valid scientific research on the etiology, pathology, and treatment of physical disorders occurs because in the world as it currently exists, there are impairments and threats to physical functioning. One could, in principle, not value physical health, but if any culture were to in 53

Copyright American Psychological Association. Not for further distribution.

Widiger and Crego

fact reject physical health as a local value judgment, this culture would be unlikely to survive. Valuing adequate or optimal physical functioning is indeed a natural, evolutionary result of existing within a world in which there are threats to survival. Likewise, in the world as it currently exists, there are impairments and threats to adequate psychological functioning. Valuing optimal psychological health is likely to be important for the optimal functioning of any society or culture. Placing a value on adequate, necessary, or optimal psychological functioning might again be inherent to and a natural result of current existence. Any particular definition of what would constitute adequate, necessary, or optimal psychological functioning will likely be biased to a degree by local cultural values, but this would only be the failing of one particular conceptualization of mental disorder (i.e., a weak rather than a strong critique). The value judgment that is inherent to the concept of a mental disorder is not reflective of local, cultural values; it is an inherent and necessary result of current existence. Valuing adequate, necessary, or optimal psychological functioning is a logical and natural result of existing in a world in which there are threats to psychological functioning, just as placing a value on adequate, necessary, or optimal physical functioning would be a logical and natural result of existing in a world in which there are threats to physical functioning (Widiger, 2002). Different societies, cultures, and even persons within a particular culture will disagree as to what constitutes optimal or pathological biological and psychological functioning (López & Guarnaccia, 2016; Sadler, 2005). It is not at all straightforward how best to understand the differences between cultures with respect to what constitutes health, dysfunction, and pathology. There are two fundamental methods of cross-cultural validation, the etic and the emic (Pike, 1954). The etic approach applies a particular construct or measure across the universe of different cultures, testing whether it maintains consistent construct validity. The emic approach identifies and explores the constructs indigenous to a particular culture. Simply because diagnostic criterion sets are applied reliably across different cultures (i.e., etic cross-cultural validation) does not 54

necessarily indicate that the constructs themselves are recognized or meaningful within these cultures. However, it is unclear why it should be necessary for the establishment of a disorder’s construct validity to obtain universal (emic) acceptance. A universally accepted diagnostic system will have an international consensus validity (Kessler, 1999), but it is also apparent that belief systems vary in their validity or accuracy. Recognition of and appreciation for alternative belief systems is important for adequate functioning within an international community. However, respect for alternative belief systems does not necessarily imply that all belief systems are equally valid (Widiger, 2002). Simply because a behavior pattern is valued, accepted, encouraged, or even statistically normative within a particular culture does not necessarily mean it is conducive to healthy psychological functioning. In sum, it is important for research on cross-cultural variation to go beyond simply identifying differences in behaviors and beliefs across different cultures. This research also needs to address the fundamental question of whether these differences actually question the validity of a universal conceptualization of psychopathology (i.e., strong critique) or suggest instead simply different perspectives (i.e., weak critique) on a shared universal recognition of the value of mental health and the existence of psychopathology. SHIFTING TO A DIMENSIONAL MODEL OF CLASSIFICATION “DSM–IV-TR [was] a categorical classification that divides mental disorders into types based on criterion sets with defining features” (American Psychiatric Association, 2000, p. xxxi). This categorical classification is consistent with the medical tradition in which it is believed (and often confirmed in other areas of medicine) that mental disorders have specific etiologies, pathologies, and treatments (Zachar & Kendler, 2007). The intention of the diagnostic manual is to help the clinician determine which particular disorder is present, the diagnosis of which would indicate the presence of a specific pathology that would explain the occurrence of the symptoms and suggest a specific treatment that

Copyright American Psychological Association. Not for further distribution.

Diagnosis and Classification of Psychopathology

would ameliorate the patient’s suffering (Frances et al., 1995; Kendell, 1975). It is evident, however, that the diagnostic manuals of the American Psychiatric Association have routinely failed in guiding clinicians to the identification of one specific disorder. Despite the best efforts of the authors of each edition to revise the criterion sets to increase their specificity, multiple diagnoses, arbitrary boundaries, complex heterogeneity among persons sharing the same diagnoses, and substantial numbers of persons falling through the diagnostic cracks remain the norm (Lilienfeld & Treadway, 2016; Widiger & Samuel, 2005). As acknowledged early in the process by the chair and vice chair of DSM–5, In the more than 30 years since the introduction of the Feighner criteria by Robins and Guze, which eventually led to DSM–III, the goal of validating these syndromes and discovering common etiologies has remained elusive. Despite many proposed candidates, not one laboratory marker has been found to be specific in identifying any of the DSM–defined syndromes. Epidemiologic and clinical studies have shown extremely high rates of comorbidities among the disorders, undermining the hypothesis that the syndromes represent distinct etiologies. Furthermore, epidemiologic studies have shown a high degree of short-term diagnostic instability for many disorders. With regard to treatment, lack of treatment specificity is the rule rather than the exception. (Kupfer, First, & Regier, 2002, p. xviii) Kupfer et al. (2002) did perhaps overstate the limitations and failures of the diagnostic manual, but it does indeed appear to be the case that mental disorders are the result of a complex array of biological vulnerabilities and dispositions that interact with a number of environmental and psychosocial events that exert their progressive effects over a developing period of time (Rutter, 2003). The symptoms and pathologies of mental disorders are highly responsive to a wide variety of neurobiological,

interpersonal, cognitive, and other mediating and moderating variables that help to develop, shape, and form a particular individual’s psychopathology profile. This complex etiological history and individual psychopathology profile are unlikely to be well described by single diagnostic categories that attempt to make distinctions at nonexistent discrete joints (Widiger & Samuel, 2005). It was suggested at the first DSM–5 Research Planning Conference that it would be “important that consideration be given to advantages and disadvantages of basing part or all of DSM–V on dimensions rather than categories” (Rounsaville et al., 2002, p. 12). This initial conference was followed by a series of international meetings whose purpose was to further enrich the empirical database in preparation for the eventual development of DSM–5. The first of these meetings was devoted to shifting personality disorders to a dimensional model of classification (Widiger, Simonsen, Krueger, Livesley, & Verheul, 2005). The final conference was devoted to dimensional approaches across the diagnostic manual, including substance use disorders, major depressive disorder, psychoses, anxiety disorders, and developmental psychopathology, as well as the personality disorders (Helzer, Kraemer, et al., 2008). Nevertheless, there was also considerable opposition to any such paradigm shift to a dimensional model of classification (e.g., Kendler & First, 2010; Shedler et al., 2010). In addition, it was apparently never the intention of the authors of DSM–5 to replace diagnostic categories with dimensional models of classification. “What [was] being proposed for DSM–V is not to substitute dimensional scales for categorical diagnoses, but to add a dimensional option to the usual categorical diagnoses for DSM–V” (Kraemer, 2008, p. 9). Proposals for DSM–5 were to be confined to “supplementary dimensional approaches to the categorical definitions that would also relate back to the categorical definitions” (Helzer, Wittchen, et al., 2008, p. 116). The introduction to DSM–5 explicitly acknowledges the failure of the categorical model: “the once plausible goal of identifying homogeneous populations for treatment and research resulted in narrow diagnostic categories that did not capture clinical reality, symptom heterogeneity within disorders, 55

Copyright American Psychological Association. Not for further distribution.

Widiger and Crego

and significant sharing of symptoms across multiple disorders” (American Psychiatric Association, 2013, p. 12). It is further asserted that dimensional approaches will “supersede current categorical approaches in coming years” (p. 13). In addition, there were indeed some revisions to the diagnostic manual that reflected the preference to eventually shift the manual to a dimensional model (American Psychiatric Association, 2013). Autism and schizophrenia are now explicitly conceptualized as spectrum disorders, with different variants existing along a common dimension of underlying pathology. The problematic distinction between substance abuse and dependence was abandoned in favor of a level of severity. Reference is made in the introduction of the manual to the broad dimensions of internalizing and externalizing dysfunction that cut across existing categories. Finally, included in Section III of DSM–5 for emerging models and measures is a fivedomain, 25-trait dimensional model of maladaptive personality functioning (Krueger et al., 2011; see also Chapter 23, this volume) that is aligned conceptually and empirically with the five-factor dimensional model of general personality structure developed within psychology. As stated in DSM–5, “these five broad domains are maladaptive variants of the five domains of the extensively validated and replicated personality model known as the ‘Big Five,’ or the Five Factor Model of personality” (American Psychiatric Association, 2013, p. 773). SHIFTING TO A NEUROBIOLOGICAL MODEL The first edition of the DSM (American Psychiatric Association, 1952) and DSM–II (American Psychiatric Association, 1968) favored a psychodynamic perspective (Spitzer et al., 1980). The authors of DSM–III therefore removed terms (e.g., neurosis) that appeared to refer explicitly to psychodynamic constructs in order to have the manual be atheoretical, or at least be reasonably neutral with respect to alternative models of psychopathology (Spitzer et al., 1980). However, it appears that all theoretical perspectives have found the atheoretical language to be less than optimal for their own particular perspective (Widiger, 2016). Interpersonal and 56

systems theoretical perspectives, which consider dysfunctional behavior to be the result of a pathology of a wider social system rather than simply within the individual, consider the organismic diagnoses of DSM–5 to be fundamentally incompatible with their perspective (Reiss & Emde, 2003). Psychodynamically oriented clinicians bemoan the fact that succeeding editions of the manual have become increasingly objective, descriptive, and atheoretical, lacking an explicit reference to the inferred dynamic mechanisms of psychoanalytic theory and practice. Therefore, they have developed their own manual, the Psychodynamic Diagnostic Manual (Psychodynamic Diagnostic Manual Task Force, 2006). Behaviorists argue that the organismic perspective of DSM–5 is inconsistent with the situational context of dysfunctional behavior (Follette & Houts, 1996). Even neurobiologically oriented psychiatry is unhappy. “Although there is a large body of research that indicates a neurobiological basis for most mental disorders, the DSM definitions are virtually devoid of biology” (Charney et al., 2002, pp. 31–32). The neurobiological perspective, however, has been explicitly embraced by the National Institute of Mental Health (NIMH), a primary funding agency for mental health research. The past three directors of NIMH (Cuthbert & Insel, 2013; Hyman, 2010; Insel, 2013) share the disgruntled frustration of the chair and vice chair of DSM–5 (Kupfer et al., 2002) with respect to the lack of apparently sufficient progress in the identification of specific etiologies, pathologies, and treatments. However, NIMH blames this on the American Psychiatric Association’s diagnostic manual (Cuthbert & Insel, 2013; Hyman, 2010)—more specifically, on its failure to embrace a neurobiological reductionism. “Unlike our definitions of ischemic heart disease, lymphoma, or AIDS, the DSM diagnoses are based on a consensus about clusters of clinical symptoms, not any objective laboratory measure” (Insel, 2013, para. 2). NIMH has taken the position that “mental disorders are biological disorders involving brain circuits that implicate specific domains of cognition, emotion, or behavior” (para. 3), and it has indicated that it will be reluctant to fund studies that are concerned with the syndromes of DSM–5. “It is critical to realize

Copyright American Psychological Association. Not for further distribution.

Diagnosis and Classification of Psychopathology

that we cannot succeed if we use DSM categories” (para. 4). NIMH has identified five broad domains of functioning it wishes to fund (i.e., negative valence systems, positive valence systems, cognitive systems, systems for social processes, and arousal–modulatory systems), collectively known as the Research Domain Criteria (RDoC; Sanislow et al., 2010). It is evident that NIMH will favor those studies with a neurobiological orientation. “The first step is to inventory the fundamental, primary behavioral functions that the brain has evolved to carry out, and to specify the neural systems that are primarily responsible for implementing these functions” (Cuthbert & Insel, 2013, p. 4). It might become difficult for psychodynamic, cognitive–behavioral, or social–interpersonal systems researchers to obtain funding unless they can present their study within a neurobiological or cognitive neuroscience orientation (Insel, 2009). For example, NIMH has posted seven suggested units of RDoC analysis (Lilienfeld & Treadway, 2016). Five of the seven are explicitly biological (i.e., genes, molecules, cells, circuits, and physiology). Berenbaum (2013) expressed the concern that studies at the level of psychological variables concerning beliefs, emotions, and behavior might not be well received. It has long been recognized that “the most direct and informative approach to learning about a person’s problems, attributes, motivations, and resources is to ask the person directly” (Butcher, Bubany, & Mason, 2013, p. 171). Although several RDoC articles proclaim an embracement of psychosocial and developmental research (e.g., Morris & Cuthbert, 2012), Cuthbert and Kozak (2013) acknowledged that “Berenbaum is right in supposing that research that relies exclusively on self-report data would fall outside of the RDoC approach” (p. 933). Psychopathology involves, in part, dysregulation along various neurochemical pathways, but this neurochemistry interacts with and occurs within the context of psychological, sociological, and cultural variables that also play a significant role. The contribution of sociological, cultural, cognitive, and interpersonal variables is unlikely to be well understood through biological reductionism (Satel & Lilienfeld,

2013). A person is not just a neurochemical mechanism. A person is also a psychological being who exists in a social world. As suggested by Kendler (2005, 2012), mental disorders need to be understood at all levels of explanation, from the biological to the psychological and the cultural. “It is unlikely that cultural [and psychological] forces that shape psychopathology can be efficiently understood at the level of basic brain biology” (Kendler, 2005, p. 436). Biology, psychology, and culture interact and influence one another, and each level of explanation should probably be acknowledged if a comprehensive and complete understanding of psychopathology is to occur. For example, the depression of an adult woman who was repeatedly sexually abused throughout childhood is unlikely to be adequately understood as simply a dysregulation along a serotonergic pathway that would optimally be treated with an antidepressant medication that would suppress her feelings of depression. There is more to her story than simply the neurochemical dysregulation. The optimal treatment will likely require an understanding of the meaning and significance of the sexual abuse in the context of her ongoing social and familial relationships. She might in fact no longer feel depressed over having been sexually abused as a result of a biological treatment, but this does not necessarily suggest that she received the optimal treatment. Nevertheless, it would appear that NIMH will give priority to the further development of pharmacological (neurobiological) treatment with less attention to CBT (Frances & Widiger, 2012; Goldfried, 2016). It is difficult, if not impossible, to create a diagnostic manual that is entirely atheoretical or even neutral. However, the authors of the manual should probably make an effort to remain above the competitive fray of competing theoretical models rather than embrace one particular perspective. As expressed by the American Psychiatric Association (2013), DSM–5 is “used by clinicians and researchers from different orientations (biological, psychodynamic, cognitive, behavioral, interpersonal, family/systems), all of whom strive for a common language to communicate the essential characteristics of mental disorders” (p. xlii). A language that 57

Copyright American Psychological Association. Not for further distribution.

Widiger and Crego

purposely favors one particular perspective will not provide an equal playing field and will subtly if not explicitly bias scientific research and discourse (Frances et al., 1989; Stengel, 1959; Wakefield, 1998; Widiger & Mullins-Sweatt, 2008). Nevertheless, NIMH has taken the position of embracing one particular theoretical model. With respect to NIMH funding, the biological theoretical perspective has essentially usurped the playing field. Not surprisingly, NIMH has received criticism for this decision (e.g., Frances, 2014; Wakefield, 2014; Weinberger & Goldberg, 2014), but these objections are unlikely to cause any fundamental change to its commitment to a neurobiological model of psychopathology. The DSM–5 is perhaps to be commended for resisting the pressure of neurobiological psychiatry to favor this theoretical model to the detriment of all other theoretical perspectives. An initial proposal had been made to revise the definition of mental disorder in DSM–5 to require that it “[reflect] an underlying psychobiological dysfunction” (Stein et al., 2010, p. 1761), but this proposed requirement was ultimately rejected. DSM–5 will likely be considerably more userfriendly to psychodynamic, cognitive–behavioral, and interpersonal–systems clinicians and researchers than NIMH’s RDoC system. CONCLUSION The importance of a having an authoritative, uniform classification of psychopathology has long been and repeatedly recognized (e.g., Farr, 1839; Kendell, 1975; Salmon et al., 1917; Sartorius et al., 1993; Stengel, 1959). The costs to clinical practice and research if there was no uniform nomenclature would be enormous. Everybody appears to find fault with this language, but there is at least the ability to communicate disagreement in a meaningful manner. Communication among researchers, theorists, and clinicians of different or even common theoretical persuasions would be severely handicapped by the absence of this common language. Nevertheless, as an official diagnostic nomenclature, DSM–5 and ICD–10 are powerful documents. They have considerable impact not only on how psychopathology is diagnosed but also on how it is 58

understood, addressed, and treated. The development of any such authoritative diagnostic system is a heady responsibility. Given the many controversies that beset DSM–5, Frances (2013) suggested that future editions of DSM–5 be given to a more professionally neutral organization, such as the National Academies Institute of Medicine (Health and Medicine Division). The American Psychiatric Association, however, is likely to maintain its authoritative control over the DSM. Perhaps the next edition will be informed by the concerns and problems that were generated by the fifth edition. Work has already begun on the next edition. The American Psychiatric Association switched from Roman (DSM–IV) to Arabic (DSM–5) numerals to denote editions because the process will now include ongoing, interim revisions to sections of the manual, whenever there appears to be sufficient justification. These revisions are being governed by a standing oversight committee. Presumably, any such revisions (e.g., DSM–5.1) will not involve major changes, only adjustments to a particular section, perhaps at best providing a transition to an eventual DSM–6. However, the precise process and scope for how this ongoing revision will occur remains to be determined.

References American Psychiatric Association. (1952). Diagnostic and statistical manual: Mental disorders. Washington, DC: Author. American Psychiatric Association. (1968). Diagnostic and statistical manual of mental disorders (2nd ed.). Washington, DC: Author. American Psychiatric Association. (1980). Diagnostic and statistical manual of mental disorders (3rd ed.). Washington, DC: Author. American Psychiatric Association. (1987). Diagnostic and statistical manual of mental disorders (3rd ed., rev. ed.). Washington, DC: Author. American Psychiatric Association. (1994). Diagnostic and statistical manual of mental disorders (4th ed.). Washington, DC: Author. American Psychiatric Association. (2000). Diagnostic and statistical manual of mental disorders (4th ed., text revision). Washington, DC: Author. American Psychiatric Association. (2010a). Classification issues under discussion. Retrieved June 12, 2010, from http://www.dsm5.org/ProposedRevisions/Pages/ ClassificationIssuesUnderDiscussion.aspx

Diagnosis and Classification of Psychopathology

American Psychiatric Association. (2010b). Complex somatic symptom disorder. Retrieved June 12, 2010, from http://www.dsm5.org/ProposedRevisions/Pages/ proposedrevision.aspx?rid=368 American Psychiatric Association. (2010c). Pathological gambling. Retrieved June 12, 2010, from http://www.dsm5.org/ProposedRevisions/Pages/ proposedrevision.aspx?rid=210

Copyright American Psychological Association. Not for further distribution.

American Psychiatric Association. (2012a). Board of trustees principles. Retrieved June 29, 2012, from http://www. dsm5.org/about/Pages/BoardofTrusteePrinciples.aspx American Psychiatric Association. (2012b). Cyclothymic disorder. Retrieved June 29, 2012, from http://www.dsm5.org/ProposedRevisions/Pages/ proposedrevision.aspx?rid=158# American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). Washington, DC: Author. Bagby, R. M., Watson, C., & Ryder, A. G. (2012). Depressive personality disorder. In T. A. Widiger (Ed.), Oxford handbook of personality disorders (pp. 628–647). New York, NY: Oxford University Press. Barsky, A. J., Wyshak, G., & Klerman, G. L. (1992). Psychiatric comorbidity in DSM–III–R hypochondriasis. Archives of General Psychiatry, 49, 101–108. http://dx.doi.org/10.1001/ archpsyc.1992.01820020021003 Bayer, R., & Spitzer, R. L. (1982). Edited correspondence on the status of homosexuality in DSM–III. Journal of the History of the Behavioral Sciences, 18, 32–52. Berenbaum, H. (2013). Classification and psychopathology research. Journal of Abnormal Psychology, 122, 894–901. http://dx.doi.org/10.1037/ a0033096 Bergner, R. M. (1997). What is psychopathology? And so what? Clinical Psychology: Science and Practice, 4, 235–248. http://dx.doi.org/10.1111/j.14682850.1997.tb00112.x Blashfield, R. K., Keeley, J. W., Flanagan, E. H., & Miles, S. R. (2014). The cycle of classification: DSM–I through DSM–5. Annual Review of Clinical Psychology, 10, 25–51. http://dx.doi.org/10.1146/ annurev-clinpsy-032813-153639 Bouman, T. K., & Eifert, G. H. (2009). Somatoform disorders. In P. H. Blaney & T. Millon (Eds.), Oxford textbook of psychopathology (pp. 482–505). New York, NY: Oxford University Press.

with self-report inventories. In K. Geisinger, B. A. Bracken, J. F. Carlson, J.-I. Hansen, N. R. Kuncel, S. P. Reise, & M. C. Rodriguez (Eds.), APA handbook of testing and assessment in psychology: Vol. 2. Testing and assessment in clinical and counseling psychology (pp. 171–192). http://dx.doi.org/10.1037/14048-011 Charney, D. S., Barlow, D. H., Botteron, K., Cohen, J. D., Goldman, D., Gur, R. E., . . . Zaleman, S. J. (2002). Neuroscience research agenda to guide development of a pathophysiologically based classification system. In D. J. Kupfer, M. B. First, & D. A. Regier (Eds.), A research agenda for DSM–V (pp. 31–84). Washington, DC: American Psychiatric Association. Child and Adolescent Disorders Work Group. (2010). Justification for temper dysregulation disorder with dysphoria. Retrieved June 12, 2010, from http://www.dsm5.org/ProposedRevisions/Pages/ proposedrevision.aspx?rid=397# Clarke, D. E., Narrow, W. E., Regier, D. A., Kuramoto, S. J., Kupfer, D. J., Kuhl, E. A., & Kraemer, H. C. (2013). DSM–5 field trials in the United States and Canada, Part I: Study design, sampling strategy, implementation, and analytic approaches. American Journal of Psychiatry, 170, 43–58. Cuthbert, B. N., & Insel, T. R. (2013). Toward the future of psychiatric diagnosis: The seven pillars of RDoC. BMC Medicine, 11, 126. http://dx.doi.org/ 10.1186/1741-7015-11-126 Cuthbert, B. N., & Kozak, M. J. (2013). Constructing constructs for psychopathology: The NIMH research domain criteria. Journal of Abnormal Psychology, 122, 928–937. http://dx.doi.org/10.1037/a0034028 Decker, H. S. (2010). A moment of crisis in the history of American psychiatry. Retrieved from http:// historypsychiatry.wordpress.com/2010/04/27/amoment-of-crisis-in-the-history-of-americanpsychiatry Escobar, J. I., Gara, M., Silver, R. C., Waitzkin, H., Holman, A., & Compton, W. (1998). Somatisation disorder in primary care. British Journal of Psychiatry, 173, 262–266. http://dx.doi.org/10.1192/ bjp.173.3.262 Farr, W. (1839). First annual report. Southport, England: General Registrar Office for England and Wales. Fawcett, J. (2010). An overview of mood disorders in the DSM–5. Current Psychiatry Reports, 12, 531–538. http://dx.doi.org/10.1007/s11920-010-0154-2

Buss, D. M., Haselton, M. G., Shackelford, T. K., Bleske, A. L., & Wakefield, J. C. (1998). Adaptations, exaptations, and spandrels. American Psychologist, 53, 533–548. http://dx.doi.org/10.1037/0003-066X.53.5.533

Fink, P., Ørnbøl, E., Toft, T., Sparle, K. C., Frostholm, L., & Olesen, F. (2004). A new, empirically established hypochondriasis diagnosis. American Journal of Psychiatry, 161, 1680–1691. http://dx.doi.org/10.1176/ appi.ajp.161.9.1680

Butcher, J. N., Bubany, S., & Mason, S. N. (2013). Assessment of personality and psychopathology

First, M. B. (2010). Clinical utility in the revision of the Diagnostic and statistical manual of mental disorders 59

Copyright American Psychological Association. Not for further distribution.

Widiger and Crego

(DSM). Professional Psychology: Research and Practice, 41, 465–473. http://dx.doi.org/10.1037/ a0021511 First, M. B. (2016). The importance of developmental field trials in the revision of psychiatric classification. Lancet, 3, 579–584. First, M. B., & Pincus, H. A. (2002). The DSM–IV text revision: Rationale and potential impact on clinical practice. Psychiatric Services, 53, 288–292. http://dx.doi.org/10.1176/appi.ps.53.3.288 First, M. B., Pincus, H. A., Levine, J. B., Williams, J. B. W., Ustun, B., & Peele, R. (2004). Clinical utility as a criterion for revising psychiatric diagnoses. American Journal of Psychiatry, 161, 946–954. http://dx.doi.org/ 10.1176/appi.ajp.161.6.946 First, M. B., Reed, G. M., Hyman, S. E., & Saxena, S. (2015). The development of the ICD-11 clinical descriptions and diagnostic guidelines for mental and behavioural disorders. World Psychiatry, 14, 82–90. http://dx.doi.org/10.1002/wps.20189 Follette, W. C., & Houts, A. C. (1996). Models of scientific progress and the role of theory in taxonomy development: A case study of the DSM. Journal of Consulting and Clinical Psychology, 64, 1120–1132. http://dx.doi.org/10.1037/0022-006X.64.6.1120 Frances, A. (2014). RDoC is necessary, but very oversold. World Psychiatry, 13, 47–49. http://dx.doi.org/ 10.1002/wps.20102 Frances, A. J. (2013). Saving normal. NY: HarperCollins. Frances, A. J., First, M. B., & Pincus, H. A. (1995). DSM–IV guidebook. Washington, DC: American Psychiatric Publishing. Frances, A. J., First, M. B., Widiger, T. A., Miele, G. M., Tilly, S. M., Davis, W. W., & Pincus, H. A. (1991). An A to Z guide to DSM–IV conundrums. Journal of Abnormal Psychology, 100, 407–412. http://dx.doi.org/ 10.1037/0021-843X.100.3.407 Frances, A. J., & Widiger, T. (2012). Psychiatric diagnosis: Lessons from the DSM–IV past and cautions for the DSM–5 future. Annual Review of Clinical Psychology, 8, 109–130. http://dx.doi.org/ 10.1146/annurev-clinpsy-032511-143102 Frances, A. J., Widiger, T. A., & Pincus, H. A. (1989). The development of DSM–IV. Archives of General Psychiatry, 46, 373–375. http://dx.doi.org/10.1001/ archpsyc.1989.01810040079012 Frick, P. J., Ray, J. V., Thornton, L. C., & Kahn, R. E. (2014). Can callous-unemotional traits enhance the understanding, diagnosis, and treatment of serious conduct problems in children and adolescents? A comprehensive review. Psychological Bulletin, 140, 1–57. http://dx.doi.org/10.1037/a0033076 Garb, H. N. (2005). Clinical judgment and decision making. Annual Review of Clinical Psychology,

60

1, 67–89. http://dx.doi.org/10.1146/annurev. clinpsy.1.102803.143810 Garb, H. N., Lilienfeld, S. O., & Fowler, K. A. (2016). Psychological assessment and clinical judgment. In J. E. Maddux & B. A. Winstead (Eds.), Psychopathology: Foundations for a contemporary understanding (4th ed., pp. 111–126). New York, NY: Routledge. Goldfried, M. R. (2016). On possible consequences of National Institute of Mental Health funding for psychotherapy research and training. Professional Psychology: Research and Training, 47, 77–83. Greenberg, G. (2013). The book of woe: The DSM and the unmaking of psychiatry. New York, NY: Blue Rider Press. Gureje, O. (2015). Classification of somatic syndromes in ICD-11. Current Opinion in Psychiatry, 28, 345–349. http://dx.doi.org/10.1097/YCO.0000000000000186 Helzer, J. E., Kraemer, H. C., Krueger, R. F., Wittchen, H.-U., Sirovatka, P. J., & Regier, D. A. (Eds.). (2008). Dimensional approaches in diagnostic classification. Washington, DC: American Psychiatric Association. Helzer, J. E., Wittchen, H.-U., Krueger, R. F., & Kraemer, H. C. (2008). Dimensional options for DSM–V: The way forward. In J. E. Helzer, H. C. Kraemer, R. F. Krueger, H.-U. Wittchen, P. J. Sirovatka, & D. A. Regier (Eds.), Dimensional approaches to diagnostic classification: Refining the research agenda for DSM–V (pp. 115–127). Washington, DC: American Psychiatric Association. Horwitz, A. V., & Wakefield, J. C. (2007). The loss of sadness: How psychiatry transformed normal sorrow into depressive disorder. New York, NY: Oxford University Press. Hyman, S. E. (2010). The diagnosis of mental disorders: The problem of reification. Annual Review of Clinical Psychology, 6, 155–179. http://dx.doi.org/10.1146/ annurev.clinpsy.3.022806.091532 Insel, T. R. (2009). Translating scientific opportunity into public health impact: A strategic plan for research on mental illness. Archives of General Psychiatry, 66, 128–133. http://dx.doi.org/10.1001/ archgenpsychiatry.2008.540 Insel, T. R. (2013). Post by former NIMH director Thomas Insel: Transforming diagnosis. Retrieved from http://www.nimh.nih.gov/about/director/2013/ transforming-diagnosis.shtml International Advisory Group for the Revision of ICD–10 Mental and Behavioural Disorders. (2011). A conceptual framework for the revision of the ICD–10 classification of mental and behavioural disorders. World Psychiatry, 10, 86–92. http://dx.doi.org/ 10.1002/j.2051-5545.2011.tb00022.x

Diagnosis and Classification of Psychopathology

Jones, K. D. (2012). A critique of the DSM–5 field trials. Journal of Nervous and Mental Disease, 200, 517–519. http://dx.doi.org/10.1097/NMD.0b013e318257c699 Kafka, M. P. (2010). Hypersexual disorder: A proposed diagnosis for DSM–V. Archives of Sexual Behavior, 39, 377–400. http://dx.doi.org/10.1007/s10508-0099574-7

Copyright American Psychological Association. Not for further distribution.

Kapur, S., Phillips, A. G., & Insel, T. R. (2012). Why has it taken so long for biological psychiatry to develop clinical tests and what to do about it? Molecular Psychiatry, 17, 1174–1179. http://dx.doi.org/10.1038/ mp.2012.105 Kendell, R., & Jablensky, A. (2003). Distinguishing between the validity and utility of psychiatric diagnoses. American Journal of Psychiatry, 160, 4–12. http://dx.doi.org/10.1176/appi.ajp.160.1.4 Kendell, R. E. (1975). The role of diagnosis in psychiatry. London, England: Blackwell Scientific. Kendler, K. S. (1990). Toward a scientific psychiatric nosology: Strengths and limitations. Archives of General Psychiatry, 47, 969–973. http://dx.doi.org/ 10.1001/archpsyc.1990.01810220085011 Kendler, K. S. (2005). Toward a philosophical structure for psychiatry. American Journal of Psychiatry, 162, 433–440. http://dx.doi.org/10.1176/appi. ajp.162.3.433 Kendler, K. S. (2010). A statement from Kenneth S. Kendler, M.D., on the proposal to eliminate the grief exclusion criterion from major depression, by Kenneth S. Kendler, M.D., Member, DSM–5 Mood Disorder Work Group. Retrieved June 12, 2010, from http://www.dsm5.org/Pages/Default.aspx Kendler, K. S. (2012). The dappled nature of causes of psychiatric illness: Replacing the organic-functional/ hardware-software dichotomy with empirically based pluralism. Molecular Psychiatry, 17, 377–388. http://dx.doi.org/10.1038/mp.2011.182 Kendler, K. S. (2013). A history of the DSM–5 scientific review committee. Psychological Medicine, 43, 1793–1800. http://dx.doi.org/10.1017/ S0033291713001578 Kendler, K. S., & First, M. B. (2010). Alternative futures for the DSM revision process: Iteration v. paradigm shift. British Journal of Psychiatry, 197, 263–265. http://dx.doi.org/10.1192/bjp.bp.109.076794 Kendler, K. S., Kupfer, D., Narrow, W., Phillips, K., & Fawcett, J. (2009). Guidelines for making changes to DSM–V. Unpublished manuscript. Kendler, K. S., Muñoz, R. A., & Murphy, G. (2010). The development of the Feighner criteria: A historical perspective. American Journal of Psychiatry, 167, 134–142. http://dx.doi.org/10.1176/appi. ajp.2009.09081155

Kessler, R. C. (1999). The World Health Organization International Consortium in Psychiatric Epidemiology (ICPE): Initial work and future directions—The NAPE Lecture 1998. Acta Psychiatrica Scandinavica Supplementum, 99, 2–9. http://dx.doi.org/10.1111/ j.1600-0447.1999.tb05378.x Kirk, S. A. (Ed.). (2005). Mental disorders in the social environment: Critical perspectives. New York, NY: Columbia University Press. Kirmayer, L. J., & Young, A. (1999). Culture and context in the evolutionary concept of mental disorder. Journal of Abnormal Psychology, 108, 446–452. http://dx.doi.org/10.1037/0021-843X.108.3.446 Klein, D. F. (1999). Harmful dysfunction, disorder, disease, illness, and evolution. Journal of Abnormal Psychology, 108, 421–429. http://dx.doi.org/ 10.1037/0021-843X.108.3.421 Kraemer, H. C. (2008). DSM categories and dimensions in clinical and research contexts. In J. E. Helzer, H. C. Kraemer, R. F. Krueger, H.-U. Wittchen, P. J. Sirovatka, & D. A. Regier (Eds.), Dimensional approaches to diagnostic classification: Refining the research agenda for DSM–V (pp. 5–17). Washington, DC: American Psychiatric Association. Krueger, R. F., Eaton, N. R., Derringer, J., Markon, K. E., Watson, D., & Skodol, A. E. (2011). Personality in DSM–5: Helping delineate personality disorder content and framing the metastructure. Journal of Personality Assessment, 93, 325–331. http://dx.doi.org/ 10.1080/00223891.2011.577478 Kupfer, D. J., Angst, J., Berk, M., Dickerson, F., Frangou, S., Frank, E., . . . Zarate, C. A. (2011). Advances in bipolar disorder: Selected sessions from the 2011 International Conference on Bipolar Disorder. Annals of the New York Academy of Sciences, 1242, 1–25. http://dx.doi.org/10.1111/j.1749-6632.2011.06336.x Kupfer, D. J., First, M. B., & Regier, D. A. (Eds.). (2002). Introduction. In D. J. Kupfer, M. B. First, & D. A. Regier (Eds.), A research agenda for DSM–V (pp. xv–xxiii). Washington, DC: American Psychiatric Association. Lilienfeld, S. O., & Marino, L. (1999). Essentialism revisited: Evolutionary theory and the concept of mental disorder. Journal of Abnormal Psychology, 108, 400–411. http://dx.doi.org/10.1037/ 0021-843X.108.3.400 Lilienfeld, S. O., & Treadway, M. T. (2016). Clashing diagnostic approaches: DSM–ICD versus RDoC. Annual Review of Clinical Psychology, 12, 435–463. http://dx.doi.org/10.1146/ annurev-clinpsy-021815-093122 López, S. R., & Guarnaccia, P. J. (2016). Cultural dimensions of psychopathology: The social world’s impact on mental disorders. In J. E. Maddux & B. A.

61

Widiger and Crego

Winstead (Eds.), Psychopathology: Foundations for a contemporary understanding (4th ed., pp. 59–75). New York, NY: Routledge. Maddux, J. E., Gosselin, J. T., & Winstead, B. A. (2016). Conceptions of psychopathology: A socialconstructionist perspective. In J. E. Maddux & B. A. Winstead (Eds.), Psychopathology: Foundations for a contemporary understanding (4th ed., pp. 3–17). New York, NY: Routledge.

Copyright American Psychological Association. Not for further distribution.

Markon, K. E. (2013). Epistemological pluralism and scientific development: An argument against authoritative nosologies. Journal of Personality Disorders, 27, 554–579. http://dx.doi.org/10.1521/ pedi.2013.27.5.554 Meehl, P. E. (1986). Diagnostic taxa as open concepts: Metatheoretical and statistical questions about reliability and construct validity in the grand strategy of nosological revision. In T. Millon & G. L. Klerman (Eds.), Contemporary directions in psychopathology: Toward the DSM–IV (pp. 215–231). New York, NY: Guilford Press. Mood Disorders and Childhood and Adolescent Disorders Work Group. (2010). Issues pertinent to a developmental approach to bipolar disorder. Retrieved June 12, 2010, from http://www.dsm5.org/ProposedRevisions/Pages/ proposedrevision.aspx?rid=397# Morey, L. C., & Benson, K. T. (2016). An investigation of adherence to diagnostic criteria, revisited: Clinical diagnosis of the DSM–IV/DSM–5 section II personality disorders. Journal of Personality Disorders, 30, 130–144. Morris, S. E., & Cuthbert, B. N. (2012). Research domain criteria: Cognitive systems, neural circuits, and dimensions of behavior. Dialogues in Clinical Neuroscience, 14, 29–37. Mullins-Sweatt, S. N., Lengel, G. J., & DeShong, H. L. (2016). The importance of considering clinical utility in the construction of a diagnostic manual. Annual Review of Clinical Psychology, 12, 133–155. http://dx.doi.org/10.1146/annurev-clinpsy021815-092954 Mullins-Sweatt, S. N., & Widiger, T. A. (2009). Clinical utility and DSM–V. Psychological Assessment, 21, 302–312. http://dx.doi.org/10.1037/a0016607 Petry, N. M. (2006). Should the scope of addictive behaviors be broadened to include pathological gambling? Addiction, 101(Suppl. 1), 152–160. http://dx.doi.org/10.1111/j.1360-0443.2006.01593.x Pike, K. L. (1954). Language in relation to a unified theory of the structure of human behavior. The Hague, the Netherlands: Mouton. Psychodynamic Diagnostic Manual Task Force (2006). Psychodynamic diagnostic manual. Silver Spring, MD: Alliance of Psychoanalytic Organizations.

62

Reed, G. M. (2010). Toward ICD–11: Improving the clinical utility of WHO’s International Classification of Mental Disorders. Professional Psychology: Research and Practice, 41, 457–464. http://dx.doi.org/ 10.1037/a0021701 Regier, D. A., & Narrow, W. E. (2002). Defining clinically significant psychopathology with epidemiologic data. In J. E. Hulzer & J. J. Hudziak (Eds.), Defining psychopathology in the 21st century: DSM–V and beyond (pp. 19–30). Washington, DC: American Psychiatric Publishing. Regier, D. A., Narrow, W. E., Clarke, D. E., Kraemer, H. C., Kuramoto, S. J., Kuhl, E. A., & Kupfer, D. J. (2013). DSM–5 field trials in the United States and Canada, Part II: Test-retest reliability of selected categorical diagnoses. American Journal of Psychiatry, 170, 59–70. http://dx.doi.org/10.1176/appi. ajp.2012.12070999 Regier, D. A., Narrow, W. E., Kuhl, E. A., & Kupfer, D. J. (2009). The conceptual development of DSM–V. American Journal of Psychiatry, 166, 645–650. http://dx.doi.org/10.1176/appi.ajp.2009.09020279 Reiss, D., & Emde, R. N. (2003). Relationship disorders are psychiatric disorders: Five reasons they were not included in DSM–IV. In K. A. Phillips, M. B. First, & H. A. Pincus (Eds.), Advancing DSM: Dilemmas in psychiatric diagnosis (pp. 191–223). Washington, DC: American Psychiatric Association. Robins, E., & Guze, S. B. (1970). Establishment of diagnostic validity in psychiatric illness: Its application to schizophrenia. American Journal of Psychiatry, 126, 983–987. http://dx.doi.org/10.1176/ ajp.126.7.983 Rounsaville, B. J., Alarcon, R. D., Andrews, G., Jackson, J. S., Kendell, R. E., Kendler, K. S., & Kirmayer, L. J. (2002). Toward DSM–V: Basic nomenclature issues. In D. J. Kupfer, M. B. First, & D. A. Regier (Eds.), A research agenda for DSM–V (pp. 1–30). Washington, DC: American Psychiatric Publishing. Rutter, M. (2003, October). Pathways of genetic influences on psychopathology. Zubin Award Address at the 18th annual meeting of the Society for Research in Psychopathology, Toronto, Ontario, Canada. Sadler, J. Z. (2005). Values and psychiatric diagnosis. Oxford, England: Oxford University Press. Salmon, T. W., Copp, O., May, J. V., Abbot, E. S., & Cotton, H. A. (1917). Report of the Committee on Statistics of the American Medico-Psychological Association. American Journal of Insanity, 74, 255–260. Sanislow, C. A., Pine, D. S., Quinn, K. J., Kozak, M. J., Garvey, M. A., Heinssen, R. K., . . . Cuthbert, B. N. (2010). Developing constructs for psychopathology research: Research domain criteria. Journal of

Diagnosis and Classification of Psychopathology

Abnormal Psychology, 119, 631–639. http://dx.doi.org/ 10.1037/a0020909 Sartorius, N., Kaelber, C. T., Cooper, J. E., Roper, M. T., Rae, D. S., Gulbinat, W., . . . Regier, D. A. (1993). Progress toward achieving a common language in psychiatry: Results from the field trial of the clinical guidelines accompanying the WHO classification of mental and behavioral disorders in ICD–10. Archives of General Psychiatry, 50, 115–124. http://dx.doi.org/ 10.1001/archpsyc.1993.01820140037004

Copyright American Psychological Association. Not for further distribution.

Satel, S., & Lilienfeld, S. O. (2013). Brainwashed: The seductive appeal of mindless neuroscience. New York, NY: Basic Books. Schatzberg, A. F., Scully, J. H., Kupfer, D. J., & Regier, D. A. (2009). Setting the record straight: A response to Frances commentary on DSM–V. Psychiatric Times, 26(8), 1–2. Shaffer, H. J., LaPlante, D. A., & Nelson, S. E. (Eds.). (2012). APA addiction syndrome handbook (2 vols.). Washington, DC: American Psychological Association. Shedler, J., Beck, A., Fonagy, P., Gabbard, G. O., Gunderson, J., Kernberg, O., . . . Westen, D. (2010). Personality disorders in DSM–5. American Journal of Psychiatry, 167, 1026–1028. http://dx.doi.org/ 10.1176/appi.ajp.2010.10050746 Skodol, A. E. (2012). Personality disorders in DSM–5. Annual Review of Clinical Psychology, 8, 317–344. http://dx.doi.org/10.1146/ annurev-clinpsy-032511-143131 Spiegel, D., Lewis-Fernández, R., Lanius, R., Vermetten, E., Simeon, D., & Friedman, M. (2013). Dissociative disorders in DSM–5. Annual Review of Clinical Psychology, 9, 299–326. http://dx.doi.org/10.1146/ annurev-clinpsy-050212-185531 Spitzer, R. L., Endicott, J., & Robins, E. (1975). Clinical criteria for psychiatric diagnosis and DSM–III. American Journal of Psychiatry, 132, 1187–1192. http://dx.doi.org/10.1176/ajp.132.11.1187 Spitzer, R. L., & Fleiss, J. L. (1974). A re-analysis of the reliability of psychiatric diagnosis. British Journal of Psychiatry, 125, 341–347. http://dx.doi.org/10.1192/ bjp.125.4.341 Spitzer, R. L., & Wakefield, J. C. (1999). DSM–IV diagnostic criterion for clinical significance: Does it help solve the false positives problem? American Journal of Psychiatry, 156, 1856–1864. Spitzer, R. L., & Williams, J. B. W. (1982). The definition and diagnosis of mental disorder. In W. R. Gove (Ed.), Deviance and mental illness (pp. 15–32). Beverly Hills, CA: Sage. Spitzer, R. L., Williams, J. B. W., & Skodol, A. E. (1980). DSM–III: The major achievements and an overview.

American Journal of Psychiatry, 137, 151–164. http://dx.doi.org/10.1176/ajp.137.2.151 Stein, D. J., Phillips, K. A., Bolton, D., Fulford, K. W. M., Sadler, J. Z., & Kendler, K. S. (2010). What is a mental/psychiatric disorder? From DSM–IV to DSM–V. Psychological Medicine, 40, 1759–1765. http://dx.doi.org/10.1017/S0033291709992261 Stengel, E. (1959). Classification of mental disorders. Bulletin of the World Health Organization, 21, 601–663. Strauss, M. E., & Smith, G. T. (2009). Construct validity: Advances in theory and methodology. Annual Review of Clinical Psychology, 5, 1–25. http://dx.doi.org/ 10.1146/annurev.clinpsy.032408.153639 Volkmar, F. R., & McPartland, J. C. (2014). From Kanner to DSM–5: Autism as an evolving diagnostic concept. Annual Review of Clinical Psychology, 10, 193–212. http://dx.doi.org/10.1146/ annurev-clinpsy-032813-153710 Wakefield, J. C. (1992). The concept of mental disorder: On the boundary between biological facts and social values. American Psychologist, 47, 373–388. http://dx.doi.org/10.1037/0003-066X.47.3.373 Wakefield, J. C. (1998). The DSM’s theory-neutral nosology is scientifically progressive: Response to Follette and Houts (1996). Journal of Consulting and Clinical Psychology, 66, 846–852. http://dx.doi.org/ 10.1037/0022-006X.66.5.846 Wakefield, J. C. (2001). The myth of DSM’s invention of new categories of disorder: Hout’s diagnostic discontinuity thesis disconfirmed. Behaviour Research and Therapy, 39, 575–624. Wakefield, J. C. (2011). Should uncomplicated bereavement-related depression be reclassified as a disorder in the DSM–5? Response to Kenneth S. Kendler’s statement defending the proposal to eliminate the bereavement exclusion. Journal of Nervous and Mental Disease, 199, 203–208. http://dx.doi.org/10.1097/NMD.0b013e31820cd155 Wakefield, J. C. (2014). Wittgenstein’s nightmare: Why the RDoC grid needs a conceptual dimension. World Psychiatry, 13, 38–40. http://dx.doi.org/10.1002/ wps.20097 Wakefield, J. C. (2016). Diagnostic issues and controversies in DSM–5: Return of the false positives problem. Annual Review of Clinical Psychology, 12, 105–132. http://dx.doi.org/10.1146/ annurev-clinpsy-032814-112800 Wakefield, J. C., & First, M. B. (2013). Diagnostic validity and the definition of mental disorder: A program for conceptually advancing psychiatry. Canadian Journal of Psychiatry/Revue canadienne de psychiatrie, 58, 653–655.

63

Widiger and Crego

Weinberger, D. R., & Goldberg, T. E. (2014). RDoCs redux. World Psychiatry, 13, 36–38. http://dx.doi.org/ 10.1002/wps.20096 Westen, D., Shedler, J., & Bradley, R. (2006). A prototype approach to personality disorder diagnosis. American Journal of Psychiatry, 163, 846–856. http://dx.doi.org/ 10.1176/ajp.2006.163.5.846

Copyright American Psychological Association. Not for further distribution.

Widiger, T. A. (2002). Values, politics, and science in the construction of the DSM. In J. Sadler (Ed.), Descriptions and prescriptions: Values, mental disorders, and the DSM (pp. 25–41). Baltimore, MD: Johns Hopkins University Press. Widiger, T. A. (2011). A shaky future for personality disorders. Personality Disorders: Theory, Research, and Treatment, 2, 54–67. http://dx.doi.org/10.1037/a0021855 Widiger, T. A. (2016). Classification and diagnosis: Historical developments and future issues. In J. E. Maddux & B. A. Winstead (Eds.), Psychopathology: Foundations for a contemporary understanding (4th ed., pp. 97–110). New York, NY: Routledge. Widiger, T. A., & Clark, L. A. (2000). Toward DSM–V and the classification of psychopathology. Psychological Bulletin, 126, 946–963. http://dx.doi.org/10.1037/ 0033-2909.126.6.946 Widiger, T. A., & Crego, C. (2015). Process and content of DSM–5. Psychopathology Review, 2, 162–176. http://dx.doi.org/10.5127/pr.035314 Widiger, T. A., Frances, A. J., Pincus, H. A., Davis, W. W., & First, M. B. (1991). Toward an empirical classification for the DSM–IV. Journal of Abnormal Psychology, 100, 280–288. http://dx.doi.org/ 10.1037/0021-843X.100.3.280 Widiger, T. A., Hurt, S. W., Frances, A., Clarkin, J. F., & Gilmore, M. (1984). Diagnostic efficiency and DSM–III. Archives of General Psychiatry, 41, 1005–1012. http://dx.doi.org/10.1001/ archpsyc.1984.01790210087011

64

Widiger, T. A., & Mullins-Sweatt, S. (2008). Classification. In M. Hersen & A. M. Gross (Eds.), Handbook of clinical psychology: Vol. 1. Adults (pp. 341–370). New York, NY: Wiley. Widiger, T. A., & Samuel, D. B. (2005). Diagnostic categories or dimensions: A question for Diagnostic and statistical manual of mental disorders—fifth edition. Journal of Abnormal Psychology, 114, 494–504. http://dx.doi.org/10.1037/0021843X.114.4.494 Widiger, T. A., & Sankis, L. M. (2000). Adult psychopathology: Issues and controversies. Annual Review of Psychology, 51, 377–404. http://dx.doi.org/ 10.1146/annurev.psych.51.1.377 Widiger, T. A., Simonsen, E., Krueger, R., Livesley, W. J., & Verheul, R. (2005). Personality disorder research agenda for the DSM–V. Journal of Personality Disorders, 19, 315–338. http://dx.doi.org/ 10.1521/pedi.2005.19.3.315 World Health Organization. (1992). The ICD–10 classification of mental and behavioural disorders: Clinical descriptions and diagnostic guidelines. Geneva, Switzerland: Author. Zachar, P., & Kendler, K. S. (2007). Psychiatric disorders: A conceptual taxonomy. American Journal of Psychiatry, 164, 557–565. http://dx.doi.org/10.1176/ ajp.2007.164.4.557 Zilboorg, G. (1941). A history of medical psychology. New York, NY: Norton. Zimmerman, M. (2011). A critique of the proposed prototype rating system for personality disorders in DSM–5. Journal of Personality Disorders, 25, 206–221. http://dx.doi.org/10.1521/pedi.2011.25.2.206 Zisook, S., Shear, K., & Kendler, K. S. (2007). Validity of the bereavement exclusion criterion for the diagnosis of major depressive episode. World Psychiatry, 6, 102–107.

Chapter 4

Examination of Neurological and Neuropsychological Features in Psychopathology

Copyright American Psychological Association. Not for further distribution.

Colleen E. Jackson and William P. Milberg

Neuropsychology is commonly defined as the study of brain–behavior relationships. Although the field of neuropsychology was once based in the assessment of individuals with neurological disorders, the need and usefulness of neuropsychological assessment in the mental health field has gained widespread acceptance (Yozawitz, 1986). With the increased use of neuropsychological assessment with psychiatric populations came a growing appreciation of the cognitive sequelae, both subtle and profound, within psychiatric conditions (Heaton, Baade, & Johnson, 1978). Today, neuropsychological assessment is commonly used to inform diagnostic and treatment outcomes in neurological, psychiatric, and mixed populations (Hebben & Milberg, 2009). The sheer number of individuals affected by psychiatric conditions is striking, particularly when considered within the context of substantial disability associated with mental illness. Recent published figures from the World Health Organization (2001) estimate that 450 million individuals are affected by a mental or behavioral disorder; however, this figure is likely now far surpassed. Updated prevalence figures (Kessler et al., 2009) suggest that, although variable across countries, a diagnosis of any Diagnostic and Statistical Manual of Mental Disorders (4th ed.; American Psychiatric Association, 1994) condition was present for 18.1%–36.1% of those assessed. The pervasiveness

of cognitive impairment associated with psychiatric conditions underscores the need to understand and intervene with what is likely to be a major cause of disability in these conditions. INTRODUCTION In this chapter, we present numerous mental health conditions with associated cognitive impairment. However, the reasons why these conditions are associated with cognitive impairment is less clear. In the attempt to understand cognitive impairment within the context of psychopathology, one is faced with the challenge of considering whether measurable cognitive impairment is the result of fundamental neuropathology due to the mental health condition or, alternatively, whether cognitive impairment in one or more domains is reflective of more diffuse impairment co-occurring with the psychiatric condition. For example, many of the mental health disorders discussed in this chapter are associated with memory dysfunction. However, is memory impairment fundamental to, and reflective of neurobiological dysfunction in, these disorders? Or are these problems indicative of a deficit in core cognitive functions (e.g., attention, information processing) resulting in bottom-up dysfunction? Or do more generalized cognitive deficits perhaps commonly co-occur with, yet are in fact separate

Dr. Jackson was supported by a Department of Veterans Affairs Fellowship in Advanced Geriatrics during a portion of her work on this chapter. This chapter was authored by employees of the United States government as part of official duty and is considered to be in the public domain. Any views expressed herein do not necessarily represent the views of the United States government, and the authors’ participation in the work is not meant to serve as an official endorsement. http://dx.doi.org/10.1037/0000064-004 APA Handbook of Psychopathology: Vol. 1. Psychopathology: Understanding, Assessing, and Treating Adult Mental Disorders, J. N. Butcher (Editor-in-Chief) 65 Copyright © 2018 by the American Psychological Association. All rights reserved.

APA Handbook of Psychopathology: Psychopathology: Understanding, Assessing, and Treating Adult Mental Disorders, edited by J. N. Butcher and J. M. Hooley Copyright © 2018 American Psychological Association. All rights reserved.

Copyright American Psychological Association. Not for further distribution.

Jackson and Milberg

from, these conditions? We raise this as a critical point in interpreting the neuropsychological, neurological, and neuropathological literature as it relates to psychopathology. Because many different mental health conditions may present with one or more similar areas of cognitive dysfunction, neuropsychological results cannot be used to diagnose mental disorders. Rather, the information obtained through a neuropsychological evaluation may offer significant insight into an individual’s cognitive strengths and weaknesses and may be used to inform treatment recommendations and guide educational and vocational planning. Evolving conceptualizations of psychopathology and neuroscience have transitioned focus from symptom-based diagnoses to a greater emphasis on transdiagnostic commonalities (i.e., shared dimensions of brain–behavior relationships; McTeague, 2016). Although not the focus of this chapter, we believe that the evolving diagnostic approaches described in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM–5; American Psychiatric Association, 2013) and the Research Domain Criteria (see Krueger & DeYoung, 2016) have relevance to the broader issue of conceptualizing cognition and neuropathology across psychopathological conditions. Evidence supports common neurobiological abnormalities in related disorders (Baker et al., 2014; Etkin & Wager, 2007) as well as across more diverse diagnostic groups (Goodkind et al., 2015). Common genetic polymorphisms are also associated with a number of different psychiatric conditions (Cross-Disorder Group of the Psychiatric Genomics Consortium, 2013). This chapter presents an up-to-date review of the most common mental health conditions presenting with cognitive dysfunction using a DSM–5 framework. Chapter sections are separated by diagnosis, with associated cognitive, neurological, and neuropathological dysfunction. Although we strive to present the most relevant evidence of impairment associated with the individual conditions presented in this chapter, we strongly encourage the reader to consider all evidence within a broader, transdiagnostic framework. 66

Challenges in the Assessment of Cognition The assessment of cognition has a number of challenges. These challenges exist in all assessment contexts; however, they may be particularly salient when working with individuals with a mental health condition. Motivation and effort are of particular concern in neuropsychological assessment. Suboptimal motivation can potentially complicate interpretation of assessment results and in some instances lead to an invalid examination. The role of secondary gain, including internal (e.g., receiving attention or care) or external factors (e.g., financial compensation, reduced obligations at work), should also be considered. These factors may reduce a person’s motivation to perform in a manner consistent with his or her true capabilities (Heilbronner, Sweet, Morgan, Larrabee, & Millis, 2009). In the field of neuropsychology, measures of symptom validity (symptom validity tests) and performance validity (performance validity tests) are used to provide an objective assessment of motivation and effort (Larrabee, 2012). Similarly, the use of embedded symptom validity test measures in psychological assessment (e.g., the Minnesota Multiphasic Personality Inventory—2—Restructured Form) also offers standardized, objective measurement of motivation and effort. Standardized assessment of motivation and effort is of particular importance with psychiatric populations because factors related to psychiatric conditions may affect an individual’s ability to put forth full and consistent effort. Neuropsychological assessment must also consider the extent to which an individual’s performance is reflective of his or her current pathology versus baseline cognitive abilities. This is typically described in terms of a deficit in one or more cognitive domains relative to estimated baseline (i.e., premorbid) abilities. Such abilities may be predicted on the basis of sociodemographic information (e.g., Barona equation, which incorporates patient age, sex, race, education, occupation, geographic region of residence, and urban vs. rural residence; Barona, Reynolds, & Chastain, 1984) or objective assessment (e.g., Wechsler Adult Intelligence Scale; Wechsler, 1987). The process of distinguishing

Copyright American Psychological Association. Not for further distribution.

Examination of Neurological and Neuropsychological Features in Psychopathology

between baseline functioning and cognitive changes attributable to a psychiatric disorder may be especially complicated because many psychiatric conditions begin early in life and may lack a clear point of onset, making it difficult to estimate premorbid cognitive abilities. Using neuropsychological assessment to clarify cognitive functioning is further complicated when two or more psychiatric conditions co-occur (e.g., anxiety and depression). As discussed further later in this chapter, many psychiatric conditions produce similar cognitive profiles, making it challenging to attribute specific deficits to a particular disorder in cases of multiple co-occurring conditions. We encourage readers to reflect on these challenges as they consider neuropsychological and neurological findings within psychiatric populations.

Cognitive Domains and Associated Brain Regions Before discussing the unique, and at times overlapping, cognitive impairments associated with mental health conditions, we feel it is pertinent to present descriptions of the cognitive domains included in this chapter. Although we briefly mention relevant brain structures associated with cognitive domains, this summary is not intended to be exhaustive. Readers are reminded that cognitive functions exist within a highly networked system, and although damage in a particular region may result in cognitive dysfunction, this does not necessarily indicate a direct structure-to-function relationship (Hebben & Milberg, 2009). Attention.  Attention extends well beyond the fundamental ability to encode information. Rather, attention is more appropriately defined and conceptualized as a multipart process that includes (a) sensory selection, described as the filtering of relevant and irrelevant information, as well as the focusing and automatic shifting between incoming information; (b) response selection, which includes initiating a response, inhibition of unselected responses, and active switching; (c) attentional capacity, which is dependent on arousal, effort, and motivation; and (d) sustained performance, which describes the ability to maintain attention, although performance

is influenced by vigilance and fatigability (Strauss, Sherman, & Spreen, 2006). Assessment and description of attentional processes is complicated by a number of factors, including inconsistent use of terminology and overlap in attentional processes both conceptually (i.e., attentional processes cannot be evaluated in isolation and there is frequent overlap with other neurocognitive domains, such as executive function) and in practice (i.e., frequent overlap in attentional processes assessed in a given test; Strauss et al., 2006). Executive functioning.  Perhaps even more so than attention, executive functioning represents the use of a single term to describe a multitude of functions. Multiple authors in the past 10 to 15 years have attempted to define the core aspects of executive functioning (e.g., Baron, 2004; Gioia, Isquith, Guy, & Kenworthy, 2000; Lezak, Howieson, & Loring, 2004), with most authors describing a system that functions in a supervisory capacity and enables the execution of purposeful and goaldirected actions. This type of functioning is dependent on the ability to plan, respond, and flexibly adjust in response to changing information. Consequently, impairments in executive functioning may result in alterations in social comportment, judgment, decision making, organizing and executing behaviors, modifying and switching, and aspects of memory (J. G. Scott & Schoenberg, 2011). Damage to the prefrontal lobes, particularly the orbital and medial regions, has consistently been associated with behavioral and personality changes. However, damage to limbic structures (e.g., amygdala), thalamic nuclei, and right hemisphere structures may also result in notable changes in personality (e.g., apathy) and behavior (e.g., planning, organization, and execution). Verbal and nonverbal memory.  Memory includes three component processes: (a) encoding (the processing of information to be stored), (b) consolidation (strengthening of representations while stored), and (c) retrieval (accessing stored information). The studies included in this chapter typically focus on the encoding and retrieval of consciously learned and recalled information (i.e., declarative memory). 67

Jackson and Milberg

Copyright American Psychological Association. Not for further distribution.

Multiple brain regions are implicated in memory, including the temporal lobes, medial temporal structures (i.e., hippocampus, entorhinal and perirhinal cortices, amygdala), diencephalon (i.e., thalamus, hypothalamus), and basal forebrain (see Kolb & Whishaw, 2003). Visuospatial functioning.  Visuospatial functioning encompasses higher order vision abilities, including visuoperception (i.e., identifying the object) and spatial processing (i.e., identifying the location of the object). A dorsal visual pathway, projecting from the primary visual field through the parietal lobe, has been shown to be involved in spatial processing, resulting in deficits in locating objects in space and hemispatial neglect. In contrast, a ventral visual pathway, connecting the striate and temporal lobe, has been associated with object identification; damage to this pathway results in impairments in face and object recognition. Language.  The assessment of language typically includes evaluation, whether formal or informal, of fluency, comprehension, and repetition. In addition, assessment of receptive and expressive vocabulary, naming, and word generation (i.e., phonemic [letter] and semantic [category] fluency) are commonly

included. The left hemisphere contains many of the critical areas for language production, including speech output (e.g., Broca’s area in the left prefrontal region) and comprehension (e.g., Wernicke’s area in the left temporoparietal region). Access to semantic information, on which naming tasks and semantic word generation tasks are dependent, is commonly associated with the functioning of the left anterior temporal lobe. In contrast, phonemic generation tasks are more broadly mediated by frontalexecutive systems. Motor functioning.  Motor functioning is commonly assessed via standardized tasks requiring manual dexterity and motor speed. However, it should also be noted that many motor tasks are also affected by attention, executive functioning, and visuospatial abilities.

Neurological and Neuropathological Factors Associated With Psychopathology In an effort to provide relevant background to understanding associated neuropathological correlates of psychiatric disorders, we present a brief reference table that provides an overview of relevant brain regions and associated functions and disorders (Table 4.1). Readers are encouraged to refer back to

Table 4.1 Relevant Brain Regions and Associated Functions and Disorders Brain region and structure

Function and involvement in mental

Relevant mental health conditions

health conditions Limbic system  Amygdalaa   Anterior cingulate cortexb   Cingulate gyrusa  Hippocampusa   Insular cortex   Orbitofrontal cortexb  Thalamusb Frontal cortexb

Sense and identify fear and anxiety; initiate emotional response Self-monitoring; motivation; sustained attention Involved in the emotional response Potentially affected by neurochemical alterations Internal regulation system controlling visceromotor, neuroendocrine, pulmonary systems, pain Involved in the emotional response Involved in emotional responding, homeostasis Involved in control of the behavioral response; social awareness

Note. aBlumenfeld (2010). bHarrison (2002). 68

Anxiety disorders Depression; bipolar disorder; schizophrenia Anxiety disorders Depression; bipolar disorder; posttraumatic stress disorder Posttraumatic stress disorder; social anxiety disorder Depression; bipolar disorder; anxiety disorders Depression; bipolar disorder Depression; bipolar disorder; anxiety disorders

Copyright American Psychological Association. Not for further distribution.

Examination of Neurological and Neuropsychological Features in Psychopathology

this table as they progress through the neurological and neuropathological subsections relevant to each disorder. In addition, the role of soft neurological signs, describing abnormal motor, sensory, or integrative motor–sensory presentations that do not localize to a central nervous system lesion (Rossi, De Cataldo, et al., 1990), are also presented when relevant. Examples include motor impairments, such as dyspraxia (difficulty carrying out voluntary movements), dyskinesia (problems in movement), and impairments in sensory abilities such as left–right discrimination and stereognosis (the ability to perceive and recognize the form of an object without seeing it). In the sections that follow, we describe several psychiatric conditions with prominent neuropsychological and neurological features: major depressive disorder, bipolar disorder, panic disorder, social phobia, generalized anxiety disorder, posttraumatic stress disorder (PTSD), and schizophrenia. MAJOR DEPRESSIVE DISORDER Major depressive disorder (MDD) is one of the most common mental health conditions in the United States, with a prevalence estimate of 6.7% among all U.S. adults (Substance Abuse and Mental Health Services Administration, 2014). Cognitive deficits associated with MDD, including attention, executive functioning, psychomotor and processing speed, and verbal and visual memory (immediate and delayed) are associated with psychosocial impairment (see Evans, Iverson, Yatham, & Lam, 2014, for a review).

Neuropsychological Findings Intellectual functioning.  The effect of MDD on intellectual functioning has been a topic of uncertainty for decades. Inconsistent findings may be, at least in part, attributable to variability in the clinical severity of the patient group, use of measures to assess intellectual functioning, and poorly matched control samples. The existence of intellectual differences between patients with MDD and healthy controls is equivocal; patients with MDD have been found to have IQs lower than (Sørensen, Sæbye, Urfer-Parnas, Mortensen, & Parnas, 2012), equal

to (Granick, 1963), and greater than (Robertson & Taylor, 1985) normal controls. In addition, research comparing currently depressed individuals, previously depressed but currently euthymic individuals, and controls who have never been depressed has found that a history of depression (either current or lifetime) was associated with significantly worse performance on tests of global cognition (i.e., Dementia Rating Scale and Mini-Mental State Examination; Koenig et al., 2015). The role of premorbid intellectual functioning on conferring risk for the development of depression is also an area of extensive study. Higher childhood cognitive abilities have been associated with fewer symptoms of depression and anxiety during adulthood (Hatch et al., 2007; Koenen et al., 2009). Cognitive reserve, conceptualized as a factor that may confer protection from or vulnerability for the clinical expression of sequelae associated with brain pathology (Stern, 2009), has been proposed as a factor influencing risk for the development of depression and other neuropsychiatric disorders (Barnett, Salmond, Jones, & Sahakian, 2006). Attention and executive functioning.  Attention and executive functioning are consistently identified as areas of impairment among individuals with MDD. A systematic review and meta-analysis identified high rates of reduced concentration and indecisiveness among individuals with MDD (Trivedi & Greer, 2014). This study also noted the not inconsequential effects on function associated with these attentional impairments. Specific effects on selective attention (Landrø, Stiles, & Sletvold, 2001), working memory (Cotrena, Branco, Shansis, & Fonseca, 2016; Landrø et al., 2001), focused and divided attention (Cotrena et al., 2016), and processing speed (Koenig et al., 2015) have also been identified. MDD is also associated with deficits in aspects of executive functioning (e.g., Gohier et al., 2009). For example, Lee, Hermens, Porter, and RedobladoHodge (2012) identified small to medium effect size differences between patients experiencing their first episode of MDD and healthy controls on measures of attentional switching (Hedges’s g = .22) and cognitive flexibility (Hedges’s g = .53). Similarly, other meta-analyses have found MDD to be reliably associated with impaired performance on measures of 69

Jackson and Milberg

Copyright American Psychological Association. Not for further distribution.

executive functioning (Snyder, 2013; Wagner, Doering, Helmreich, Lieb, & Tadi´c, 2012). There is also evidence that greater depression symptom severity may be associated with more impaired executive functioning (McDermott & Ebmeier, 2009). Learning and memory.  Reductions in learning and memory are prominent cognitive effects associated with MDD (Koenig et al., 2015). In fact, deficits in episodic memory are arguably the most prominent disturbance associated with depression (Zakzanis, Leach, & Kaplan, 1998). For example, Landrø et al. (2001) identified significantly worse verbal delayed memory (i.e., worse performance on seven subtasks, including a list learning paradigm, associative learning task, and short story, with delayed recall 4–5 minutes and 24 hours after initial exposure) among MDD patients compared with controls. Metaanalytic findings based on 14 studies of patients who varied in MDD duration also identified a positive relationship between symptom severity and worse verbal episodic memory (weighted M = .31), but not visuospatial memory (weighted population effect size r = .11; McDermott & Ebmeier, 2009). In contrast, Lee et al. (2012) identified significant deficits in visual learning and memory in a sample of individuals in a first episode of MDD (Hedges’s g = .53) Visuospatial functioning.  Visuospatial impairment is less commonly identified among individuals with MDD; however, Koenig et al. (2015) reported significantly worse visuospatial abilities, including construction using colored blocks and drawing of simple and complex figures, among a sample of older adults (mean age = 72.51 years) with a history of depression, either current or lifetime, than among individuals without a history of depression. In addition, Rossi, Stratta, et al. (1990) identified significantly worse performance among young to middle aged (mean age = 47 years) severely depressed patients than among controls on the Rey Complex Figure Task (J. E. Meyers & Meyers, 1995) copy and immediate recall trials. Language.  Phonemic fluency (i.e., a measure of the ability to generate words beginning with an identified letter; also referred to as letter fluency) has repeatedly been identified as an area of impairment 70

among individuals with MDD (Koenig et al., 2015; Landrø et al., 2001; Lee et al., 2012). Cross-sectional (Fossati, Amar, Raoux, Ergis, & Allilaire, 1999) and meta-analytic (Wagner et al., 2012) findings with patients with unipolar depression identified significant impairment in semantic fluency (i.e., a measure of the ability to generate words belonging to a specific category). However, there is noted variability across studies, including assessment of verbal fluency (see Henry & Crawford, 2005, for a review and meta-analysis). Specifically, Henry and Crawford (2005) identified generally greater impairment on measures of semantic relative to phonemic fluency. However, when examining studies in which assessment of both semantic and phonemic fluency were included for the same participants, the deficit for semantic fluency was only marginally larger than the deficit for phonemic fluency (rs = .43 for semantic fluency and .39 for phonemic fluency), which was interpreted as suggesting a more generalized fluency deficit. Notably, a meta-analysis of 14 studies concluded that symptom severity is not significantly associated with poorer semantic memory (weighted population effect size r = .17; McDermott & Ebmeier, 2009). Motor and sensory functioning.  Psychomotor disturbance (i.e., slowing or retardation vs. agitation) is one of the only objectively measurable symptoms of endogenous depression (see Schrijvers, Hulstijn, & Sabbe, 2008, and Sobin & Sackeim, 1997, for reviews). Psychomotor retardation and agitation are not mutually exclusive. For example, a study of 23 hospitalized depressed patients identified increased frequency of self-touching but decreased direct eye contact, smiling, and eyebrow movement (Jones & Pansa, 1979). In addition, task complexity does not appear to modulate psychomotor symptoms, because Sabbe, Hulstijn, van Hoof, and Zitman (1996; Sabbe, Hulstijn, van Hoof, TuynmanQua, & Zitman, 1999) identified fine motor slowing on both less demanding tests (e.g., drawing lines and simple figures) and tests with greater cognitive effort (e.g., tasks requiring coordination, visuospatial storage, planning, and sequencing). Evidence has suggested that age may influence psychomotor disturbances, such that patients younger than age 40 are more likely to experience

Copyright American Psychological Association. Not for further distribution.

Examination of Neurological and Neuropsychological Features in Psychopathology

psychomotor retardation, and patients older than age 40 are more likely to experience agitation (Hamilton, 1967; Winokur, Morrison, Clancy, & Crowe, 1973). Sex may also affect psychomotor symptoms, although the findings are equivocal, and evidence ranges from suggesting that males experience greater psychomotor retardation than females (Avery & Silverman, 1984; Winokur et al., 1973), females experience greater psychomotor retardation than males (Khan, Gardner, Prescott, & Kendler, 2002; Kornstein et al., 2000), to a lack of sexdependent differences (Hildebrandt, Stage, & Kragh-Soerensen, 2003a, 2003b). Changes in speech output are also commonly noted among depressed patients. Increased speech pause time (Greden, Albala, Smokler, Gardner, & Carroll, 1981; Hoffmann, Gonze, & Mendlewicz, 1985; Nilsonne, 1987; Szabadi, Bradshaw, & Besson, 1976), paucity of speech, slowed responses, monotonic phrases, and poor articulation (Hoffmann et al., 1985) are more frequently seen in depressed patients than in controls. Cannizzaro, Harel, Reilly, Chappell, and Snyder (2004) also identified a correlation between Hamilton Depression Rating Scale score (Hamilton, 1967) and slower speaking rate and reduced pitch variation. One of the greatest concerns related to psychomotor slowing among depressed individuals may be the association between psychomotor retardation and slowed motor response and decision times (Lapierre & Butter, 1980). This finding may have real-world application in the performance of tasks such as driving, which requires rapid cognitive and motor responses. Bulmash et al. (2006) found that, after controlling for age and sleepiness, depressed, nonmedicated outpatients exhibited slower steering reaction times than did controls. They also had an increased number of crashes when tested on a driving simulator.

Cognitive Functioning After Major Depressive Disorder Remission Findings reflect a persistence of cognitive deficits during MDD remission (Hammar, Lund, & Hugdahl, 2003; Neu, Kiesslinger, Schlattmann, & Reischies, 2001). Specific findings have identified continued impairment in attention (Bora, Harrison, Yücel, &

Pantelis, 2013; Paelecke-Habermann, Pohl, & Leplow, 2005) and executive functioning (Boeker et al., 2012; Paelecke-Habermann et al., 2005). The persistence of cognitive deficits after remission has been hypothesized to reflect trait features associated with chronic MDD (e.g., Hammar et al., 2003; Paelecke-Habermann et al., 2005). In addition, others have proposed possible relations between the duration of illness and structural brain changes (e.g., Sheline, Sanghavi, Mintun, & Gado, 1999), which may also explain persisting deficits. Interestingly, there is also evidence to support improvement in some aspects of cognitive functioning during MDD remission. For example, memory deficits appear to be related to depression severity and, as a result, performances improve after remission (Biringer et al., 2007; Boeker et al., 2012; Gualtieri, Johnson, & Benedict, 2006; PaeleckeHabermann et al., 2005). Notably, the literature examining cognitive functioning during remission is complicated by variable definitions to establish the extent of symptom remission, diverse methodological strategies, and heterogeneous clinical characteristics of patients (see Hasselbalch, Knorr, & Kessing, 2011, for a review).

Cognitive Effects Associated With Late-Life Major Depressive Disorder Late-life depression, defined as MDD in adults older than age 60, is of tremendous clinical concern. These individuals present with notable cognitive impairment that is significant in its own right. Impairments related to depression may also mask or confound the assessment and diagnosis of other neurological conditions affecting cognition (e.g., dementia). The nature of cognitive impairments associated with the onset of depression after age 60 appears to be broad, with noted deficits in processing speed and executive functioning (Alexopoulos, 2002). Additional deficits in psychomotor impairment (Beheydt et al., 2015), episodic memory, and visuospatial abilities are also commonly identified (Butters et al., 2004). As with their younger counterparts, depressed older adults continue to experience cognitive symptoms, particularly on executive tasks, processing speed, and working memory, after remission of 71

Jackson and Milberg

Copyright American Psychological Association. Not for further distribution.

mood symptoms (Butters et al., 2000; Nebes et al., 2003). In fact, treatment with pharmacotherapy has been found to have a limited effect on cognition in depressed older adults (B. S. Meyers, Mattis, Gabriele, & Kakuma, 1991). Cognitive abilities also appear to be related to future symptomatology and functional outcomes; poor executive functioning in depressed older adults has been shown to predict greater functional disability (Kiosses & Alexopoulos, 2005).

Neurological and Neuropathological Findings Neuropathology.  Multiple neuropathological changes have been associated with MDD in adults. Frontal, midbrain, and limbic regions are most consistently implicated, with evidence of decreased volume in the frontotemporal region (Vasic et al., 2015), prefrontal cortex (PFC), dorsolateral prefrontal cortex (DLPFC), subgenual region of the anterior cingulate cortex (ACC), basal ganglia, amygdala, and hippocampus (Campbell & MacQueen, 2006). There is also decreased density of neurons in the hippocampus (Tsopelas et al., 2011), orbitofrontal cortex (Cotter, Hudson, & Landau, 2005; Rajkowska et al., 1999), and PFC (Cotter et al., 2002; Rajkowska et al., 1999). In addition, a reduction in the number and density of pyramidal cells in the orbitofrontal cortex and ACC and reductions in pyramidal cell volumes in the DLPFC (see Kim, Nunes, Oliveira, Young, & Lafer, 2016, for a review) have been described. MDD has also been associated with altered brain network functioning. Specifically, relative to control participants, functional neuroimaging with individuals with MDD has demonstrated decreased activity in the DLPFC and increased activity in the ventrolateral PFC (Brody, Barsom, Bota, & Saxena, 2001). Furthermore, there is evidence of particular abnormalities in ACC and DLPFC inputs from the amygdala (Drevets, 2000), as well as reduced cerebral blood flow in the ACC and bilateral parahippocampal areas, with increased blood flow in the frontoparietal and striatal regions (Vasic et al., 2015). Meta-analytic findings from fluorodeoxyglucose– positron emission tomography studies identified 72

lower metabolism in bilateral insula, left lentiform nucleus putamen, and right caudate and cingulate gyrus; however, right thalamus pulvinar and declive of the posterior limb and left culmen of vermis in the anterior lobe were significantly increased (Su et al., 2014). Furthermore, evidence of decreased metabolic activity during depressive episodes has also been identified in the DLPFC, dorsomedial PFC, subgenual region of the ACC, basal ganglia, and hippocampus, and increased activity has been identified in the ventrolateral and orbital PFC and amygdala (Davidson, Pizzagalli, Nitschke, & Putnam, 2002). Soft neurological signs associated with MDD.  Evidence has suggested that hypoesthesia of the malleolus (i.e., reduced sense of touch on the bony projections on the ankle) may be a soft neurological sign associated with MDD (Livianos et al., 2015). However, other studies have failed to identify significant differences in soft neurological signs between individuals with MDD and healthy controls using standard soft sign assessments, including motor coordination, sensory integration, and disinhibition (Zhao et al., 2013).

Conclusions Interpreting findings from the MDD literature is complicated by considerable variability in participant inclusion/exclusion criteria, depression severity within patient groups, and control of factors with potential cognitive and/or neurologic sequelae (e.g., medications, psychotic symptoms) (Evans et al., 2014). Additionally, the role of effort and engagement must be considered when evaluating individuals with MDD. For example, Rohling, Green, Allen, and Iverson (2002) found that depression had no effect on objective cognitive and psychomotor tests once patients with suboptimal effort were excluded from analyses. BIPOLAR DISORDER Bipolar disorder is a disabling illness (Harvey, Wingo, Burdick, & Baldessarini, 2010) associated with significant functional impairment during acute and remitted stages. In addition, bipolar disorder is

Copyright American Psychological Association. Not for further distribution.

Examination of Neurological and Neuropsychological Features in Psychopathology

a challenging condition to treat, and relapse rates are high even after psychopharmacological intervention. For example, Gitlin, Swendsen, Heller, and Hammen (1995) found that 37% of participants diagnosed with bipolar disorder and followed in an outpatient clinic experienced a recurrence of a manic or depressive episode within 1 year. Moreover, two thirds of individuals who relapsed experienced multiple relapses. Per the diagnostic criteria of the DSM–5 (American Psychiatric Association, 2013), bipolar I disorder is characterized by the occurrence of at least one manic episode, with many individuals also experiencing one or more depressive episodes. Diagnosis of bipolar II requires current or past hypomanic episode as well as current or past major depressive episode. Cognitive impairment in bipolar disorder is not a core diagnostic criterion. However, given evidence of neurocognitive deficits across all stages of bipolar illness (manic, depressed, and euthymic), neurocognitive deficits have been proposed as an endophenotype (Hasler, Drevets, Gould, Gottesman, & Manji, 2006). Further evidence for this proposal comes from findings indicating that first-degree relatives of individuals with bipolar disorder, who are presumably at particularly elevated risk of developing a mood disorder, perform worse on tasks of verbal declarative memory as well as on some aspects of executive functioning (Robinson & Ferrier, 2006). This finding has been interpreted as suggesting that cognitive impairment may be a trait vulnerability factor for bipolar disorder that is present before the onset of clinical symptoms and that worsens as the illness progresses.

Neuropsychological Findings Intellectual functioning.  Research on intellectual functioning among patients with bipolar disorder has generally suggested that they perform about as well as healthy controls (e.g., Mann-Wrobel, Carreno, & Dickinson, 2011). However, some reports have suggested that bipolar patients may have premorbid intellectual deficits. For example, Trotta, Murray, and MacCabe (2015) identified small yet significant deficits in premorbid intellectual

functioning when it was assessed retrospectively, but not prospectively. Attention and executive functioning.  Multiple aspects of attention, including sustained attention, psychomotor speed, and processing speed, have consistently been identified as impairments among individuals with bipolar disorder relative to healthy control participants (Kurtz & Gerraty, 2009). Vrabie et al. (2015) identified significantly worse performance on measures of attention, psychomotor speed, and processing speed, regardless of disease stage (manic–hypomanic, depressed, or euthymic). In meta-analytic comparisons between healthy control participants and euthymic bipolar patients, small effect size differences were identified for auditory attention, and moderate to large effect size differences were identified for sustained visual vigilance and speeded visual scanning (Arts, Jabben, Krabbendam, & van Os, 2008; Bora, Yucel, & Pantelis, 2009; Kurtz & Gerraty, 2009). Bonnín et al. (2012) similarly found that subsyndromic euthymic bipolar patients demonstrated slower psychomotor speed relative to healthy controls. In this study, even asymptomatic euthymic patients demonstrated significantly worse performance, relative to healthy controls, on measures of psychomotor and processing speed. Comparisons between healthy controls and depressed bipolar patients have revealed deficits in visual scanning (Kurtz & Gerraty, 2009), as well as large effect size differences in processing speed (Gallagher, Gray, Watson, Young, & Ferrier, 2014). Large effect size differences were also found in comparisons between healthy controls and individuals in mixed or manic states for sustained attention and rapid visual scanning (Kurtz & Gerraty, 2009). Deficits in working memory have also been consistently identified across different bipolar states, including euthymia (Bora et al., 2009; Kurtz & Gerraty, 2009; Vrabie et al., 2015), mania– hypomania (Vrabie et al., 2015), and depression (Gallagher et al., 2014; Vrabie et al., 2015). Consistent impairments in executive functioning are similarly found across bipolar states (Martínez-Aran, Vieta, Reinares, et al., 2004; Vrabie et al., 2015). Relative to healthy controls, euthymic bipolar patients 73

Copyright American Psychological Association. Not for further distribution.

Jackson and Milberg

demonstrated impairments in multiple aspects of executive functioning, including large effect size differences in working memory (Robinson & Ferrier, 2006), inhibition, and set shifting (Arts et al., 2008; Bora et al., 2009; Kurtz & Gerraty, 2009), as well as moderate to large effect size differences for conceptual shifting, novel problem solving, perseveration (Bora et al., 2009; Kurtz & Gerraty, 2009; Robinson & Ferrier, 2006), speeded set shifting, sustained visual and auditory attention, and response inhibition (Robinson & Ferrier, 2006). Furthermore, MartínezArán, Vieta, Colom, et al. (2004) reported significantly worse performance on multiple measures of executive functioning among remitted patients in a euthymic state, even after controlling for the effects of subclinical symptomatology, age, and premorbid IQ. Even among subsyndromic euthymic bipolar patients, Bonnín et al. (2012) identified worse performance on set switching. Moderate effect size differences in set switching (d = 0.64) have been identified among depressed and mixed or manic bipolar patients, and large effect size differences in perseverations among mixed or manic bipolar patients have also been noted (Kurtz & Gerraty, 2009). Learning and memory.  Deficits in verbal learning and memory are commonly and consistently identified among patients with bipolar disorder, regardless of their clinical state (Gallagher et al., 2014; Goswami et al., 2006; Martínez-Arán, Vieta, Reinares, et al., 2004; Robinson & Ferrier, 2006). Kurtz and Gerraty (2009) identified large effect size differences in verbal learning for euthymic, mixed or manic, and depressed patient groups, as well as large effect size differences in delayed recall for mixed or manic patients and moderate differences for euthymic patients. Bonnín et al. (2012) also identified verbal learning and recall deficits in subsyndromic euthymic bipolar patients and asymptomatic patients, relative to healthy controls, and Malhi et al. (2007) reported more pronounced deficits in verbal memory during episodes of hypomania and depression among patients diagnosed with bipolar I disorder. Interestingly, Vrabie et al. (2015) found that manic patients showed greater verbal memory deficits than depressed, mixed, and euthymic 74

subgroups. Deficits in nonverbal memory have also been identified in bipolar patient groups (Bora et al., 2009), and Martínez-Arán, Vieta, Reinares, et al. (2004) reported differences between depressed patients and controls in visual learning as well as differences between both acute clinical groups and controls in visual recall. Visuospatial functioning.  Deficits in visual perception and visuospatial functioning in individuals with bipolar disorder are comparatively less severe relative to well-established attention, executive functioning, and memory deficits. Meta-analytic findings focused on patients in the euthymic stage of bipolar disorder have demonstrated small to moderate effect size differences relative to healthy controls on measures of visuoperception (i.e., copying a complex figure and ability to reproduce visually presented designs using colored blocks; Arts et al., 2008; Kurtz & Gerraty, 2009). In addition, Gallagher, Gray, and Kessels (2015) reported differences among individuals in a depressive episode, relative to healthy controls, on an object-location binding task. Language.  Impairment within the language domain is quite variable and dependent on the cognitive task and stage of the disease. For example, the existence of differences between semantic and phonemic fluency (ability to generate words belonging to a particular category or starting with a particular letter, respectively) among patients in the euthymic stage of bipolar disorder is equivocal, with some studies reporting greater impairment in semantic fluency (Arts et al., 2008; Martínez-Arán, Vieta, Colom, et al., 2004; Robinson & Ferrier, 2006), some studies reporting greater impairment in phonemic fluency (Bonnín et al., 2012), and some studies reporting comparable impairment in both (Kurtz & Gerraty, 2009). Furthermore, although Vrabie et al. (2015) reported worse performance on both semantic and phonemic fluency tasks across bipolar stages, individuals in a depressive stage were more impaired relative to other bipolar patients and healthy controls. Additional findings further support impairment in both phonemic and semantic fluency among patients in mixed or manic stages (Kurtz & Gerraty, 2009), as well as impairment in

Examination of Neurological and Neuropsychological Features in Psychopathology

phonemic fluency among patients in a depressed stage (Kurtz & Gerraty, 2009; Martínez-Arán, Vieta, Reinares, et al., 2004).

Copyright American Psychological Association. Not for further distribution.

Motor and sensory functioning.  Evidence of structural changes in the cerebellum (Baldaçara et al., 2011; Moorhead et al., 2007) has supported recent evidence of impaired implicit motor learning (i.e., learning a sequence of button presses without instruction) in bipolar patients compared with healthy controls (Chrobak et al., 2015).

Neurological and Neuropathological Findings Neuropathology.  Neuropathological changes in patients with bipolar disorder have implicated reduced hippocampal volume (Quigley et al., 2015) and frontal cortical volume (Abé et al., 2015; López-Larson, DelBello, Zimmerman, Schwiers, & Strakowski, 2002), as well as reduced gray and white matter volumes in the posterior cingulate bilaterally, right thalamus, cerebellum bilaterally, and left posterior limb of the internal capsule (Sani et al., 2016; see Haldane & Frangou, 2004, for a review). Soft neurological signs associated with bipolar disorder.  Soft neurological signs appear to be significantly increased among patients with bipolar disorder compared with healthy controls (Goswami et al., 2007; Nasrallah, Tippin, & McCalley-Whitters, 1983; Negash et al., 2004). Among a sample of euthymic patients with bipolar disorder, prevalence of soft neurological signs was high, with 54% demonstrating parkinsonism, 27% reporting akathisia, and 11% presenting with dyskinetic movements (Goswami et al., 2006). In addition, Mrad, Wassim Krir, Ajmi, Gaha, and Mechri (2016) reported higher prevalence and scores on a measure of soft neurological signs among euthymic patients with bipolar disorder and their psychiatrically healthy siblings, compared with unrelated control participants.

Conclusions Multiple clinical factors have been associated with neuropsychological dysfunction in bipolar disorder. Broadly, greater cognitive impairment has been associated with worse course of illness, particularly

with respect to the number of manic episodes, hospitalizations, and length of illness (Robinson & Ferrier, 2006), which is likely attributable to a complex combination of genetic, environmental, neurodevelopmental, and medication-related factors, as well as possible medical or psychiatric comorbidities (Balanzá-Martínez et al., 2010). Specifically, longer duration of illness and greater number of hospitalizations, suicide attempts, and manic episodes have been associated with greater memory dysfunction, and longer duration of illness was associated with diminished attention, slowness, and perseveration (Martínez-Arán, Vieta, Colom, et al., 2004). Significant clinical heterogeneity, including symptom severity, predominating symptoms (mania or depression), age at symptom onset, duration of illness (Robinson & Ferrier, 2006), number of prior manic or depressive episodes (Nehra, Chakrabarti, Pradhan, & Khehra, 2006), duration of clinical stages (manic, depression, and euthymia), and other comorbidities complicate interpretation of the literature. In addition, many of these clinical factors, as well as other methodological and statistical factors, and within-participant factors (e.g., engagement, self-esteem, sensitivity to perceived feedback) may exert a potential influence on cognitive function (Porter, Robinson, Malhi, & Gallagher, 2015). ANXIETY DISORDERS The DSM–5 includes a number of conditions under the umbrella of anxiety disorders, including panic disorder, social phobia, and generalized anxiety disorder, as well as a number of less commonly diagnosed or studied conditions not described in detail here. Anxiety disorders cost the United States billions in health care costs (Greenberg et al., 1999), and they are also associated with significant functional disability (e.g., Alonso et al., 2004), particularly among those with social anxiety and multiple anxiety disorders (Hendriks et al., 2014). Patients commonly report cognitive symptoms of varying severity with anxiety. Although the presence and severity of cognitive problems on formal objective testing varies, a number of key similarities, including deficits in complex attention, executive 75

Jackson and Milberg

functioning, encoding, and free retrieval of information, are present across the spectrum of anxiety disorders. We focus our discussion on cognitive symptoms associated with panic disorder, social phobia, and generalized anxiety disorder.

Copyright American Psychological Association. Not for further distribution.

Neuropsychological Findings Intellectual functioning.  The evidence supporting differences in estimated intellectual functioning between individuals with anxiety and healthy controls is minimal. In a study comparing individuals with panic disorder, individuals with social phobia, and healthy controls, Asmundson, Stein, Larsen, and Walker (1994) found no difference between anxiety disorder patients and healthy controls on measures of vocabulary or similarities as measured by the Wechsler Adult Intelligence Scales—Revised. However, this study did identify significant differences between the clinical groups and healthy controls on a measure of visuoconstruction (i.e., creating designs using colored blocks; Asmundson et al., 1994). Attention and executive functioning.  Deficits in cognitive processing speed on a task requiring the transcription of digit–symbol pairs has been identified among individuals with social phobia (O’Toole, Pedersen, Hougaard, & Rosenberg, 2015). However, on a less complicated visual processing task (Trails A completion time and accuracy), Airaksinen, Larsson, and Forsell (2005) found no differences in performance between individuals with any anxiety disorder compared with healthy control participants. Similarly, there were no identified differences between anxiety subtypes on this measure (Airaksinen et al., 2005). It would appear, on the basis of these findings, that task complexity plays a role in visual processing performance. Executive dysfunction, particularly set-shifting completion time, has also been identified among individuals with anxiety more generally (Airaksinen et al., 2005), as well as specifically among individuals with panic disorder (L. J. Cohen et al., 1996). Learning and memory.  Verbal memory deficits have been identified in numerous patient groups, including individuals with social phobia (Airaksinen 76

et al., 2005; Asmundson et al., 1994; O’Toole et al., 2015; although see Sachs et al., 2004), and panic disorder (Airaksinen et al., 2005; Asmundson et al., 1994). In fact, in the sample of patients examined by Asmundson et al. (1994), approximately 22% of those diagnosed with social phobia and 50% of individuals diagnosed with panic disorder were at least 2 or more standard deviations below the mean on a word-list learning task. Evidence has also supported deficits in nonverbal memory among patients with social phobia compared with healthy controls matched for education and general cognitive ability (O’Toole et al., 2015). Visuospatial functioning.  Visuospatial deficits, including construction accuracy (O’Toole et al., 2015), visuospatial processing (e.g., block design; Asmundson et al., 1994, L. J. Cohen et al., 1996), and cube drawing (Hollander et al., 1996), have been identified among individuals with social phobia. Language.  Decreased verbal fluency, including reduced phonemic (Airaksinen et al., 2005; O’Toole et al., 2015) and semantic fluency (O’Toole et al., 2015), has been identified among individuals with social phobia. Motor and sensory functioning.  No specific deficits in motor or sensory functioning are commonly reported among individuals with social phobia or panic disorder.

Neurological and Neuropathological Findings Neuropathology.  Structural abnormalities involving the cingulate cortex, precentral gyrus, precuneus, and temporal and frontal gyrus (De Bellis et al., 2002; Strawn et al., 2013) have been identified in individuals with generalized anxiety disorder. Functional abnormalities have also been identified in this group, including resting state abnormalities involving amygdala circuits (Etkin, Prater, Schatzberg, Menon, & Greicius, 2009; Liu et al., 2015), as well as task-related changes in PFC and ACC (see Mochcovitch, da Rocha Freire, Garcia, & Nardi, 2014, for a review). Among those diagnosed with panic disorder, structural changes in the amygdala (Massana et al.,

Copyright American Psychological Association. Not for further distribution.

Examination of Neurological and Neuropsychological Features in Psychopathology

2003a), parahippocampal gyrus, caudate nucleus, basal ganglia, insula (Lai, 2011; Massana et al., 2003b), ACC, and frontal and temporal areas (Asami et al., 2008; Han et al., 2008; Sobanski et al., 2010) have been identified. Functional abnormalities during functional MRI have also been identified in many of these regions. Specifically, increased activation in the amygdala, insula, and hippocampus during the presentation of agoraphobic-specific stimuli (Wittmann et al., 2011), and increased activation in the right inferior frontal area and cingulate cortex during panic anticipation and imagery exposure (Bystritsky et al., 2001) have been identified. Furthermore, abnormal functional connectivity within the default mode network (Y. W. Shin et al., 2013) and salience network (Pannekoek et al., 2013) have also been highlighted. Interestingly, evidence has not pointed to a clear pattern of structural changes associated with social phobia (e.g., Potts, Davidson, Krishnan, & Doraiswamy, 1994). Soft neurological signs associated with anxiety disorders.  Soft neurological signs, including cube drawing and mirror movement impairments, have been identified among individuals with social phobia (Hollander et al., 1996).

Conclusions Deficits in attention, executive functioning, learning and memory, visuospatial functioning, and language have been identified among patients with social anxiety and panic disorder. However, the literature examining neurocognitive functioning in these populations is relatively small and may benefit from further examination using clinical and experimental paradigms, with particular attention to symptom severity and comorbid conditions. POSTTRAUMATIC STRESS DISORDER The cognitive sequelae and related neuroimaging correlates of PTSD have been studied extensively. We present a brief review here; however, we also refer the reader to several excellent review references detailing this topic (Aupperle, Melrose, Stein, & Paulus, 2012; Hayes, Vanelzakker, & Shin, 2012; Qureshi et al., 2011; Vasterling & Brewin, 2005).

Neuropsychological Findings Intellectual functioning.  Pretrauma intelligence has been found to predict PTSD diagnosis after trauma exposure (see Bomyea, Risbrough, & Lang, 2012, for a review). In addition, PTSD symptom severity, as measured by the Clinician Administered PTSD Scale (Blake et al., 1995), has been found to be negatively correlated with estimated IQ (Gurvits et al., 2000), suggesting that it is not simply the dichotomous diagnosis but rather the potential severity of the symptoms that may contribute to a reduction in performance on measures assessing intelligence. Attention and executive functioning.  Deficits in attention and executive functioning are commonly identified among individuals with PTSD (B. E. Cohen et al., 2013; Koso & Hansen, 2006). For example, Jenkins, Langlais, Delis, and Cohen (2000) identified worse performance on measures of sustained attention, digit span, processing speed (i.e., rapid transcription of digit–symbol pairs), and set shifting among rape survivors with and without PTSD. Vasterling et al. (2002) similarly identified impairments in basic (i.e., Digit Span), and sustained attention on the Continuous Performance Test among Vietnam veterans with PTSD; sustained attention deficits were similarly found among Operation Desert Storm (Vasterling, Brailey, Constans, & Sutker, 1998) and Bosnian combat veterans with PTSD (Koso & Hansen, 2006). Learning and memory.  Studies have also indicated that individuals with PTSD performed significantly worse on verbal learning (B. E. Cohen et al., 2013; Vasterling et al., 2002; Yehuda, Golier, Tischler, Stavitsky, & Harvey, 2005) and memory trials (Yehuda et al., 2005). Nonverbal learning has been shown to be impaired among veterans with PTSD (Vasterling et al., 1998), although not consistently (e.g., Gilbertson et al., 2006). Visuospatial functioning.  Visuospatial functioning has been less well studied among individuals with PTSD. Language.  Significantly worse semantic fluency, relative to healthy controls, has been identified among adults with PTSD (B. E. Cohen et al., 2013). In addition, Koso and Hansen (2006) identified 77

Jackson and Milberg

impairment among veterans with PTSD, relative to age and IQ-matched trauma-exposed veterans without PTSD, on a sentence completion task. Motor and sensory functioning.  Assessment of motor and sensory functioning that is independent of processing speed or executive demands has been less well studied among individuals with PTSD.

Copyright American Psychological Association. Not for further distribution.

Neurological and Neuropathological Findings Neuropathology.  The literature examining neuropathological markers among individuals with anxiety has largely focused on those with PTSD. Structural abnormalities in this diagnostic group are typified by reduced anterior cingulate (e.g., Rauch et al., 2003) and hippocampal volumes (Gurvits et al., 1996; although see Golier et al., 2005). The literature examining functional changes among individuals with PTSD is also quite extensive (see Hayes et al., 2012, for a review). A number of functional imaging studies have identified increased activity in the amygdala in response to trauma-related stimuli (Pissiota et al., 2002; L. M. Shin et al., 2004) and trauma-unrelated affective stimuli (L. M. Shin et al., 2005). However, these findings are not universal (e.g., Hayes et al., 2011). Similarly, findings are also mixed with regard to hippocampal activity in those with PTSD, such that there is evidence for both increased (Thomaes et al., 2009) and decreased (Bremner et al., 2003; Hayes et al., 2011) activity in response to emotionally salient stimuli. Dysfunction in neural circuits involved in attention and emotional processing has also been identified, specifically increased dorsolateral and ventromedial PFC activity in response to threat stimuli (Hayes, Labar, Petty, McCarthy, & Morey, 2009) and reduced dorsolateral PFC activity in response to nonthreat stimuli (Hayes et al., 2009; Morey, Petty, Cooper, Labar, & McCarthy, 2008). Soft neurological signs associated with PTSD.  Among both combat veterans and women with a history of childhood sexual abuse, individuals with PTSD had a greater than average number of soft neurological signs than individuals with similar trauma exposure without PTSD. Furthermore, PTSD 78

symptom severity, as assessed using the Clinician Administered PTSD Scale (Blake et al., 1995), was significantly correlated with an average number of soft neurological signs (Gurvits et al., 2000).

Conclusions Overall, the literature supports significant neurocognitive effects associated with PTSD, including deficits in verbal learning and memory, rapid information processing, attention, and working memory (J. C. Scott et al., 2015). However, examination of the PTSD literature highlights several challenges in interpreting existing findings. The role of symptom severity is one that must be considered, particularly because it has been found to be significantly associated with worse performance on multiple aspects of cognitive functioning, even after adjusting for demographics (L. J. Cohen et al., 2013). Furthermore, the potential influence of comorbid conditions, including depression and other anxiety disorders, is one that must be considered both clinically and in evaluating the literature. SCHIZOPHRENIA The literature examining cognitive factors associated with schizophrenia and psychotic spectrum disorders is extensive; the reader is referred to several well-written review articles for additional information (Barch & Sheffield, 2014; Madre et al., 2016; Tolman & Kurtz, 2012). The relationship between cognitive deficits and functional impairment among individuals with schizophrenia has been well supported (Green, Kern, & Heaton, 2004), and conceptualization of cognitive deficits as discrete areas of weakness is now being replaced by a view reflecting a more global deficit across cognitive domains (Gold & Dickinson, 2013). In addition, although a full review of these findings is outside the scope of this chapter, it is worth noting that evidence from the second phase of the North American Prodrome Longitudinal Study (Seidman et al., 2016) has indicated that attention, working memory, and declarative memory abilities may be strong predictors of conversion to psychosis among those considered to be clinically high risk. Investigators in this study have suggested that

Examination of Neurological and Neuropsychological Features in Psychopathology

interventions targeting neurocognitive functioning may be particularly important among those at high risk for psychosis.

Copyright American Psychological Association. Not for further distribution.

Neuropsychological Findings Intellectual functioning.  Meta-analysis has demonstrated impairments in premorbid (Woodberry, Giuliano, & Seidman, 2008) and current intellectual functioning among individuals with schizophrenia. Compared with healthy control participants, Woodberry et al. (2008) reported a 0.5 standard deviation impairment in premorbid intelligence in individuals who went on to develop psychotic symptoms. Comparisons between individuals with schizophrenia and control samples have reflected medium to large effect sizes (Heinrichs & Zakzanis, 1998). Attention and executive functioning.  Impairments on tasks requiring auditory attention (i.e., Digit Span), psychomotor speed (i.e., Trails A), rapid alternation between sets of information (i.e., Trails B), and sustained attention (e.g., Continuous Performance Test) are commonly identified among individuals with schizophrenia (Heinrichs & Zakzanis, 1998). Deficits in working memory are among the most commonly reported in schizophrenia (see Forbes, Carrick, McIntosh, & Lawrie, 2009, for a review; Van Snellenberg et al., 2016). Given a lack of difference between phonological and visuospatial working memory functioning, a more generalized deficit in the central executive resource system, responsible for maintaining and modulating information over time, has been proposed to explain working memory impairments in this population (Barch & Sheffield, 2014). Finally, performance on more complex measures of executive functioning requiring novel problem solving, flexibility, and learning from feedback (i.e., the Wisconsin Card Sorting Task) is frequently impaired in this clinical group (Heinrichs & Zakzanis, 1998). However, findings from this meta-analytic study have also noted a relationship between the Wisconsin Card Sorting Task and intelligence, suggesting that impaired performance on this test may be a reflection of low general intellectual abilities (Heinrichs & Zakzanis, 1998). Learning and memory.  Impairments in verbal declarative memory are consistently reported among

individuals with schizophrenia (see Stone & Hsi, 2011, for a review), with effect sizes ranging from 1.0 to 1.5 standard deviations below comparison populations (Cirillo & Seidman, 2003; Heinrichs & Zakzanis, 1998). Deficits are greatest in the learning and encoding stage of memory (Cirillo & Seidman, 2003), relative to retrieval and recognition. Nonverbal memory performance is also impaired within this group, but greater heterogeneity across studies suggests that performance within this specific domain may be less reliable relative to verbal memory deficits (Heinrichs & Zakzanis, 1998). Visuospatial functioning.  Visuospatial functioning is less commonly assessed in studies on schizophrenia. Heinrichs and Zakzanis (1998) reported moderate effect sizes, in the range of 0.46 for Block Design, 0.60 for Line Orientation (judgment of line angles), and 0.61 for Facial Recognition, relative to comparison groups. Similar effect sizes were also reported by Dickinson, Ramsey, and Gold (2007). Language.  Performance on verbal fluency measures is also reflective of significant impairment (large Cohen’s d; Dickinson et al., 2007; Heinrichs & Zakzanis, 1998). Motor and sensory functioning.  Dickinson et al. (2007) reported moderate (finger tapping bilaterally) to large (grooved pegboard bilaterally) effect sizes between individuals with schizophrenia and control samples. In addition, there is evidence of greater involuntary dyskinetic movement abnormalities among children with multiple antecedents of schizophrenia (e.g., dyskinetic movements, psychotic-like experiences), who are considered to be at increased risk of future schizophrenia spectrum disorders, compared with children without such antecedents (MacManus et al., 2012).

Neurological and Neuropathological Findings Neuropathology.  Meta-analysis of 52 crosssectional and 16 longitudinal studies identified reductions in both whole brain and hippocampal volume, as well as increased ventricular volume, in individuals with schizophrenia compared with healthy controls (Steen, Mull, McClure, Hamer, & 79

Jackson and Milberg

Copyright American Psychological Association. Not for further distribution.

Lieberman, 2006). Evidence of abnormal neural connectivity was identified in both first-episode and chronic schizophrenia patients; however, there is considerable heterogeneity between studies (see Wheeler & Voineskos, 2014, for a review). Soft neurological signs associated with schizophrenia.  The literature on neurological soft signs in schizophrenia is extensive, with demonstrated relationships to structural and functional abnormalities (see Hüfner, Frajo-Apor, & Hofer, 2015, for a review). Total score on a measure of neurological soft signs, including sensory integration, motor coordination, motor sequencing, and other neurological impairments, was positively correlated with aspects of cognition, including spatial working memory and complex set shifting in both controls and individuals with schizophrenia (Arabzadeh et al., 2014). Furthermore, Bachmann, Degen, Geider, and Schröder (2014) described variability in neurological soft signs over the course of the disorder, although these soft signs were in almost all cases found to decrease alongside psychiatric symptoms.

Conclusions The literature focused on cognitive factors associated with schizophrenia is rich and evolving. Given the strong relationship between cognition and functional impairment within this population, there is a critical need to improve the ability to address cognitive deficits and their effects on daily activities and social functioning (Green, 2016). The development of cognitive remediation programs focused on schizophrenia is an area of great interest, and such programs have demonstrated effectiveness in this population (see Kaneko & Keshavan, 2012, for a review). CONCLUSION Cognitive dysfunction within the context of psychopathology is common and may contribute to the high rates of functional impairment found within psychiatric groups. Comparisons across psychiatric conditions underscore a number of common areas of cognitive dysfunction, including attention, memory, and execution of complex cognitive tasks (i.e., executive functioning). Given these overlapping areas of dysfunction, neuropsychological assessment cannot, 80

at this time, function as a diagnostic test for psychopathology. However, neuropsychological assessment has the potential to clarify cognitive strengths and weaknesses, inform treatment, and contribute to differential diagnosis. Because future research and clinical efforts are likely to be informed by a transdiagnostic approach, understanding common mechanisms of dysfunction from both cognitive and neurological–neuropathological views will be of increasing importance. Incorporating neuropsychological assessment into mental health treatment has the potential to contribute to improving the understanding of the cognitive impairments associated with psychiatric conditions and to use this knowledge to inform the treatment of individuals with these conditions.

References Abé, C., Ekman, C.-J., Sellgren, C., Petrovic, P., Ingvar, M., & Landén, M. (2015). Manic episodes are related to changes in frontal cortex: A longitudinal neuroimaging study of bipolar disorder 1. Brain: A Journal of Neurology, 138, 3440–3448. http://dx.doi.org/10.1093/ brain/awv266 Airaksinen, E., Larsson, M., & Forsell, Y. (2005). Neuropsychological functions in anxiety disorders in population-based samples: Evidence of episodic memory dysfunction. Journal of Psychiatric Research, 39, 207–214. http://dx.doi.org/10.1016/ j.jpsychires.2004.06.001 Alexopoulos, G. S. (2002). Frontostriatal and limbic dysfunction in late-life depression. American Journal of Geriatric Psychiatry, 10, 687–695. http://dx.doi.org/ 10.1097/00019442-200211000-00007 Alonso, J., Angermeyer, M. C., Bernert, S., Bruffaerts, R., Brugha, T. S., Bryson, H., . . . Vollebergh, W. A. (2004). Disability and quality of life impact of mental disorders in Europe: Results from the European Study of the Epidemiology of Mental Disorders (ESEMeD) project. Acta Psychiatrica Scandinavica Supplementum, 109, 38–46. http://dx.doi.org/ 10.1111/j.1600-0047.2004.00329.x American Psychiatric Association. (1994). Diagnostic and statistical manual of mental disorders (4th ed.). Washington, DC: Author. American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). Washington, DC: Author. Arabzadeh, S., Amini, H., Tehrani-Doost, M., Sharifi, V., Noroozian, M., & Rahiminejad, F. (2014). Correlation of neurological soft signs and

Examination of Neurological and Neuropsychological Features in Psychopathology

neurocognitive performance in first episode psychosis. Psychiatry Research, 220, 81–88. http:// dx.doi.org/10.1016/j.psychres.2014.07.044 Arts, B., Jabben, N., Krabbendam, L., & van Os, J. (2008). Meta-analyses of cognitive functioning in euthymic bipolar patients and their first-degree relatives. Psychological Medicine, 38, 771–785. http://dx.doi.org/ 10.1017/S0033291707001675

Copyright American Psychological Association. Not for further distribution.

Asami, T., Hayano, F., Nakamura, M., Yamasue, H., Uehara, K., Otsuka, T., . . . Hirayasu, Y. (2008). Anterior cingulate cortex volume reduction in patients with panic disorder. Psychiatry and Clinical Neurosciences, 62, 322–330. http://dx.doi.org/ 10.1111/j.1440-1819.2008.01800.x Asmundson, G. J. G., Stein, M. B., Larsen, D. K., & Walker, J. R. (1994). Neurocognitive function in panic disorder and social phobia patients. Anxiety, 1, 201–207.

Barnett, J. H., Salmond, C. H., Jones, P. B., & Sahakian, B. J. (2006). Cognitive reserve in neuropsychiatry. Psychological Medicine, 36, 1053–1064. http:// dx.doi.org/10.1017/S0033291706007501 Baron, I. S. (2004). Neuropsychological evaluation of the child. New York, NY: Oxford University Press. Barona, A., Reynolds, C. R., & Chastain, R. (1984). A demographically based index of premorbid intelligence for the WAIS-R. Journal of Consulting and Clinical Psychology, 52, 885–887. http:// dx.doi.org/10.1037/0022-006X.52.5.885 Beheydt, L. L., Schrijvers, D., Docx, L., Bouckaert, F., Hulstijn, W., & Sabbe, B. (2015). Psychomotor retardation in elderly untreated depressed patients. Frontiers in Psychiatry, 5, 196. http://dx.doi.org/ 10.3389/fpsyt.2014.00196

Aupperle, R. L., Melrose, A. J., Stein, M. B., & Paulus, M. P. (2012). Executive function and PTSD: Disengaging from trauma. Neuropharmacology, 62, 686–694. http:// dx.doi.org/10.1016/j.neuropharm.2011.02.008

Biringer, E., Mykletun, A., Sundet, K., Kroken, R., Stordal, K. I., & Lund, A. (2007). A longitudinal analysis of neurocognitive function in unipolar depression. Journal of Clinical and Experimental Neuropsychology, 29, 879–891. http://dx.doi.org/ 10.1080/13803390601147686

Avery, D., & Silverman, J. (1984). Psychomotor retardation and agitation in depression: Relationship to age, sex, and response to treatment. Journal of Affective Disorders, 7, 67–76. http://dx.doi.org/10.1016/ 0165-0327(84)90066-1

Blake, D. D., Weathers, F. W., Nagy, L. M., Kaloupek, D. G., Gusman, F. D., Charney, D. S., & Keane, T. M. (1995). The development of a Clinician-Administered PTSD Scale. Journal of Traumatic Stress, 8, 75–90. http://dx.doi.org/10.1002/jts.2490080106

Bachmann, S., Degen, C., Geider, F. J., & Schröder, J. (2014). Neurological soft signs in the clinical course of schizophrenia: Results of a meta-analysis. Frontiers in Psychiatry, 5, 185. http://dx.doi.org/10.3389/ fpsyt.2014.00185

Blumenfeld, H. (2010). Neuroanatomy through clinical cases (2nd ed.). Sunderland, MA: Sinauer Associates.

Baker, J. T., Holmes, A. J., Masters, G. A., Yeo, B. T. T., Krienen, F., Buckner, R. L., & Öngür, D. (2014). Disruption of cortical association networks in schizophrenia and psychotic bipolar disorder. JAMA Psychiatry, 71, 109–118. http://dx.doi.org/10.1001/ jamapsychiatry.2013.3469 Balanzá-Martínez, V., Selva, G., Martínez-Arán, A., Prickaerts, J., Salazar, J., González-Pinto, A., . . . Tabarés-Seisdedos, R. (2010). Neurocognition in bipolar disorders—A closer look at comorbidities and medications. European Journal of Pharmacology, 626, 87–96. http://dx.doi.org/10.1016/ j.ejphar.2009.10.018 Baldaçara, L., Nery-Fernandes, F., Rocha, M., Quarantini, L. C., Rocha, G. G. L., Guimarães, J. L., . . . Jackowski, A. (2011). Is cerebellar volume related to bipolar disorder? Journal of Affective Disorders, 135, 305–309. http://dx.doi.org/10.1016/ j.jad.2011.06.059 Barch, D. M., & Sheffield, J. M. (2014). Cognitive impairments in psychotic disorders: Common mechanisms and measurement. World Psychiatry, 13, 224–232. http://dx.doi.org/10.1002/wps.20145

Boeker, H., Schulze, J., Richter, A., Nikisch, G., Schuepbach, D., & Grimm, S. (2012). Sustained cognitive impairments after clinical recovery of severe depression. Journal of Nervous and Mental Disease, 200, 773–776. http://dx.doi.org/10.1097/ NMD.0b013e318266ba14 Bomyea, J., Risbrough, V., & Lang, A. J. (2012). A consideration of select pre-trauma factors as key vulnerabilities in PTSD. Clinical Psychology Review, 32, 630–641. http://dx.doi.org/10.1016/ j.cpr.2012.06.008 Bonnín, C. M., Sánchez-Moreno, J., Martínez-Arán, A., Solé, B., Reinares, M., Rosa, A. R., . . . Torrent, C. (2012). Subthreshold symptoms in bipolar disorder: Impact on neurocognition, quality of life and disability. Journal of Affective Disorders, 136, 650–659. http://dx.doi.org/10.1016/j.jad.2011.10.012 Bora, E., Harrison, B. J., Yücel, M., & Pantelis, C. (2013). Cognitive impairment in euthymic major depressive disorder: A meta-analysis. Psychological Medicine, 43, 2017–2026. http://dx.doi.org/10.1017/ S0033291712002085 Bora, E., Yucel, M., & Pantelis, C. (2009). Cognitive endophenotypes of bipolar disorder: A meta-analysis of neuropsychological deficits in euthymic patients 81

Jackson and Milberg

and their first-degree relatives. Journal of Affective Disorders, 113, 1–20. http://dx.doi.org/10.1016/ j.jad.2008.06.009

Copyright American Psychological Association. Not for further distribution.

Bremner, J. D., Vythilingam, M., Vermetten, E., Southwick, S. M., McGlashan, T., Staib, L. H., . . . Charney, D. S. (2003). Neural correlates of declarative memory for emotionally valenced words in women with posttraumatic stress disorder related to early childhood sexual abuse. Biological Psychiatry, 53, 879–889. http://dx.doi.org/10.1016/ S0006-3223(02)01891-7 Brody, A. L., Barsom, M. W., Bota, R. G., & Saxena, S. (2001). Prefrontal-subcortical and limbic circuit mediation of major depressive disorder. Seminars in Clinical Neuropsychiatry, 6, 102–112. http:// dx.doi.org/10.1053/scnp.2001.21837 Bulmash, E. L., Moller, H. J., Kayumov, L., Shen, J., Wang, X., & Shapiro, C. M. (2006). Psychomotor disturbance in depression: Assessment using a driving simulator paradigm. Journal of Affective Disorders, 93, 213–218. http://dx.doi.org/10.1016/ j.jad.2006.01.015 Butters, M. A., Becker, J. T., Nebes, R. D., Zmuda, M. D., Mulsant, B. H., Pollock, B. G., & Reynolds, C. F., III. (2000). Changes in cognitive functioning following treatment of late-life depression. American Journal of Psychiatry, 157, 1949–1954. http://dx.doi.org/ 10.1176/appi.ajp.157.12.1949 Butters, M. A., Whyte, E. M., Nebes, R. D., Begley, A. E., Dew, M. A., Mulsant, B. H., . . . Becker, J. T. (2004). The nature and determinants of neuropsychological functioning in late-life depression. Archives of General Psychiatry, 61, 587–595. http://dx.doi.org/ 10.1001/archpsyc.61.6.587 Bystritsky, A., Pontillo, D., Powers, M., Sabb, F. W., Craske, M. G., & Bookheimer, S. Y. (2001). Functional MRI changes during panic anticipation and imagery exposure. Neuroreport, 12, 3953–3957. http:// dx.doi.org/10.1097/00001756-200112210-00020 Campbell, S., & MacQueen, G. (2006). An update on regional brain volume differences associated with mood disorders. Current Opinion in Psychiatry, 19, 25–33. http://dx.doi.org/10.1097/ 01.yco.0000194371.47685.f2 Cannizzaro, M., Harel, B., Reilly, N., Chappell, P., & Snyder, P. J. (2004). Voice acoustical measurement of the severity of major depression. Brain and Cognition, 56, 30–35. http://dx.doi.org/10.1016/ j.bandc.2004.05.003 Chrobak, A. A., Siuda-Krzywicka, K., Siwek, G. P., Arciszewska, A., Siwek, M., Starowicz-Filip, A., & Dudek, D. (2015). Implicit motor learning in bipolar disorder. Journal of Affective Disorders, 174, 250–256. http://dx.doi.org/10.1016/ j.jad.2014.11.043 82

Cirillo, M. A., & Seidman, L. J. (2003). Verbal declarative memory dysfunction in schizophrenia: From clinical assessment to genetics and brain mechanisms. Neuropsychology Review, 13, 43–77. http://dx.doi.org/ 10.1023/A:1023870821631 Cohen, B. E., Neylan, T. C., Yaffe, K., Samuelson, K. W., Li, Y., & Barnes, D. E. (2013). Posttraumatic stress disorder and cognitive function: Findings from the Mind Your Heart study. Journal of Clinical Psychiatry, 74, 1063–1070. http://dx.doi.org/10.4088/ JCP.12m08291 Cohen, L. J., Hollander, E., DeCaria, C. M., Stein, D. J., Simeon, D., Liebowitz, M. R., & Aronowitz, B. R. (1996). Specificity of neuropsychological impairment in obsessive-compulsive disorder: A comparison with social phobic and normal control subjects. Journal of Neuropsychiatry and Clinical Neurosciences, 8, 82–85. http://dx.doi.org/10.1176/jnp.8.1.82 Cotrena, C., Branco, L. D., Shansis, F. M., & Fonseca, R. P. (2016). Executive function impairments in depression and bipolar disorder: Association with functional impairment and quality of life. Journal of Affective Disorders, 190, 744–753. http://dx.doi.org/ 10.1016/j.jad.2015.11.007 Cotter, D., Hudson, L., & Landau, S. (2005). Evidence for orbitofrontal pathology in bipolar disorder and major depression, but not in schizophrenia. Bipolar Disorders, 7, 358–369. http://dx.doi.org/10.1111/ j.1399-5618.2005.00230.x Cotter, D., Mackay, D., Chana, G., Beasley, C., Landau, S., & Everall, I. P. (2002). Reduced neuronal size and glial cell density in area 9 of the dorsolateral prefrontal cortex in subjects with major depressive disorder. Cerebral Cortex, 12, 386–394. http:// dx.doi.org/10.1093/cercor/12.4.386 Cross-Disorder Group of the Psychiatric Genomics Consortium. (2013). Identification of risk loci with shared effects on five major psychiatric disorders: A genome-wide analysis. Lancet, 381, 1371–1379. http://dx.doi.org/10.1016/S0140-6736(12)62129-1 Davidson, R. J., Pizzagalli, D., Nitschke, J. B., & Putnam, K. (2002). Depression: Perspectives from affective neuroscience. Annual Review of Psychology, 53, 545–574. http://dx.doi.org/10.1146/ annurev.psych.53.100901.135148 De Bellis, M. D., Keshavan, M. S., Shifflett, H., Iyengar, S., Dahl, R. E., Axelson, D. A., . . . Ryan, N. D. (2002). Superior temporal gyrus volumes in pediatric generalized anxiety disorder. Biological Psychiatry, 51, 553–562. http://dx.doi.org/10.1016/ S0006-3223(01)01375-0 Dickinson, D., Ramsey, M. E., & Gold, J. M. (2007). Overlooking the obvious: A meta-analytic comparison of digit symbol coding tasks and other cognitive measures in schizophrenia. Archives of

Examination of Neurological and Neuropsychological Features in Psychopathology

General Psychiatry, 64, 532–542. http://dx.doi.org/ 10.1001/archpsyc.64.5.532 Drevets, W. C. (2000). Functional anatomical abnormalities in limbic and prefrontal cortical structures in major depression. Progress in Brain Research, 126, 413–431. http://dx.doi.org/10.1016/ S0079-6123(00)26027-5

Copyright American Psychological Association. Not for further distribution.

Etkin, A., Prater, K. E., Schatzberg, A. F., Menon, V., & Greicius, M. D. (2009). Disrupted amygdalar subregion functional connectivity and evidence of a compensatory network in generalized anxiety disorder. Archives of General Psychiatry, 66, 1361–1372. http://dx.doi.org/ 10.1001/archgenpsychiatry.2009.104 Etkin, A., & Wager, T. D. (2007). Functional neuroimaging of anxiety: A meta-analysis of emotional processing in PTSD, social anxiety disorder, and specific phobia. American Journal of Psychiatry, 164, 1476–1488. http:// dx.doi.org/10.1176/appi.ajp.2007.07030504 Evans, V. C., Iverson, G. L., Yatham, L. N., & Lam, R. W. (2014). The relationship between neurocognitive and psychosocial functioning in major depressive disorder: A systematic review. Journal of Clinical Psychiatry, 75, 1359–1370. http://dx.doi.org/10.4088/ JCP.13r08939 Forbes, N. F., Carrick, L. A., McIntosh, A. M., & Lawrie, S. M. (2009). Working memory in schizophrenia: A meta-analysis. Psychological Medicine, 39, 889–905. http://dx.doi.org/10.1017/S0033291708004558 Fossati, P., Amar, G., Raoux, N., Ergis, A. M., & Allilaire, J. F. (1999). Executive functioning and verbal memory in young patients with unipolar depression and schizophrenia. Psychiatry Research, 89, 171–187. http://dx.doi.org/10.1016/ S0165-1781(99)00110-9 Gallagher, P., Gray, J. M., & Kessels, R. P. C. (2015). Fractionation of visuo-spatial memory processes in bipolar depression: A cognitive scaffolding account. Psychological Medicine, 45, 545–558. http://dx.doi.org/ 10.1017/S0033291714001676 Gallagher, P., Gray, J. M., Watson, S., Young, A. H., & Ferrier, I. N. (2014). Neurocognitive functioning in bipolar depression: A component structure analysis. Psychological Medicine, 44, 961–974. http://dx.doi.org/ 10.1017/S0033291713001487 Gilbertson, M. W., Paulus, L. A., Williston, S. K., Gurvits, T. V., Lasko, N. B., Pitman, R. K., & Orr, S. P. (2006). Neurocognitive function in monozygotic twins discordant for combat exposure: Relationship to posttraumatic stress disorder. Journal of Abnormal Psychology, 115, 484–495. http://dx.doi.org/ 10.1037/0021-843X.115.3.484 Gioia, G. A., Isquith, P. K., Guy, S. C., & Kenworthy, L. (2000). BRIEF: Behavior Rating Inventory of Executive Function professional manual. Lutz, FL: Psychological Assessment Resources.

Gitlin, M. J., Swendsen, J., Heller, T. L., & Hammen, C. (1995). Relapse and impairment in bipolar disorder. American Journal of Psychiatry, 152, 1635–1640. http://dx.doi.org/10.1176/ajp.152.11.1635 Gohier, B., Ferracci, L., Surguladze, S. A., Lawrence, E., El Hage, W., Kefi, M. Z., . . . Le Gall, D. (2009). Cognitive inhibition and working memory in unipolar depression. Journal of Affective Disorders, 116, 100–105. http://dx.doi.org/10.1016/ j.jad.2008.10.028 Gold, J. M., & Dickinson, D. (2013). “Generalized cognitive deficit” in schizophrenia: Overused or underappreciated? Schizophrenia Bulletin, 39, 263–265. http://dx.doi.org/10.1093/schbul/sbs143 Golier, J. A., Yehuda, R., De Santi, S., Segal, S., Dolan, S., & de Leon, M. J. (2005). Absence of hippocampal volume differences in survivors of the Nazi Holocaust with and without posttraumatic stress disorder. Psychiatry Research Neuroimaging, 139, 53–64. http://dx.doi.org/10.1016/ j.pscychresns.2005.02.007 Goodkind, M., Eickhoff, S. B., Oathes, D. J., Jiang, Y., Chang, A., Jones-Hagata, L. B., . . . Etkin, A. (2015). Identification of a common neurobiological substrate for mental illness. JAMA Psychiatry, 72, 305–315. http://dx.doi.org/10.1001/jamapsychiatry.2014.2206 Goswami, U., Gulrajani, C., Varma, A., Sharma, A., Ferrier, I. N., Young, A. H., & Moore, P. B. (2007). Soft neurological signs do not increase with age in euthymic bipolar subjects. Journal of Affective Disorders, 103, 99–103. http://dx.doi.org/10.1016/ j.jad.2007.01.009 Goswami, U., Sharma, A., Khastigir, U., Ferrier, I. N., Young, A. H., Gallagher, P., . . . Moore, P. B. (2006). Neuropsychological dysfunction, soft neurological signs and social disability in euthymic patients with bipolar disorder. British Journal of Psychiatry, 188, 366–373. http://dx.doi.org/10.1192/bjp.188.4.366 Granick, S. (1963). Comparative analysis of psychotic depressives with matched normal on some untimed verbal intelligence tests. Journal of Consulting Psychology, 27, 439–443. http://dx.doi.org/10.1037/ h0048616 Greden, J. F., Albala, A. A., Smokler, I. A., Gardner, R., & Carroll, B. J. (1981). Speech pause time: A marker of psychomotor retardation among endogenous depressives. Biological Psychiatry, 16, 851–859. Green, M. F. (2016). Impact of cognitive and social cognitive impairment on functional outcomes in patients with schizophrenia. Journal of Clinical Psychiatry, 77(Suppl. 2), 8–11. http://dx.doi.org/ 10.4088/JCP.14074su1c.02 Green, M. F., Kern, R. S., & Heaton, R. K. (2004). Longitudinal studies of cognition and functional outcome in schizophrenia: Implications for 83

Jackson and Milberg

MATRICS. Schizophrenia Research, 72, 41–51. http:// dx.doi.org/10.1016/j.schres.2004.09.009 Greenberg, P. E., Sisitsky, T., Kessler, R. C., Finkelstein, S. N., Berndt, E. R., Davidson, J. R. T., . . . Fyer, A. J. (1999). The economic burden of anxiety disorders in the 1990s. Journal of Clinical Psychiatry, 60, 427–435. http://dx.doi.org/10.4088/JCP.v60n0702

Copyright American Psychological Association. Not for further distribution.

Gualtieri, C. T., Johnson, L. G., & Benedict, K. B. (2006). Neurocognition in depression: Patients on and off medication versus healthy comparison subjects. Journal of Neuropsychiatry and Clinical Neurosciences, 18, 217–225. http://dx.doi.org/10.1176/ jnp.2006.18.2.217 Gurvits, T. V., Gilbertson, M. W., Lasko, N. B., Tarhan, A. S., Simeon, D., Macklin, M. L., . . . Pitman, R. K. (2000). Neurologic soft signs in chronic posttraumatic stress disorder. Archives of General Psychiatry, 57, 181–186. http://dx.doi.org/10.1001/ archpsyc.57.2.181 Gurvits, T. V., Shenton, M. E., Hokama, H., Ohta, H., Lasko, N. B., Gilbertson, M. W., . . . Pitman, R. K. (1996). Magnetic resonance imaging study of hippocampal volume in chronic, combat-related posttraumatic stress disorder. Biological Psychiatry, 40, 1091–1099. http://dx.doi.org/10.1016/ S0006-3223(96)00229-6 Haldane, M., & Frangou, S. (2004). New insights help define the pathophysiology of bipolar affective disorder: Neuroimaging and neuropathology findings. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 28, 943–960. http://dx.doi.org/ 10.1016/j.pnpbp.2004.05.040 Hamilton, M. (1967). Development of a rating scale for primary depressive illness. British Journal of Social and Clinical Psychology, 6, 278–296. http://dx.doi.org/ 10.1111/j.2044-8260.1967.tb00530.x Hammar, A., Lund, A., & Hugdahl, K. (2003). Longlasting cognitive impairment in unipolar major depression: A 6-month follow-up study. Psychiatry Research, 118, 189–196. http://dx.doi.org/10.1016/ S0165-1781(03)00075-1 Han, D. H., Renshaw, P. F., Dager, S. R., Chung, A., Hwang, J., Daniels, M. A., . . . Lyoo, I. K. (2008). Altered cingulate white matter connectivity in panic disorder patients. Journal of Psychiatric Research, 42, 399–407. http://dx.doi.org/10.1016/ j.jpsychires.2007.03.002 Harrison, P. J. (2002). The neuropathology of primary mood disorder. Brain: A Journal of Neurology, 125, 1428–1449. http://dx.doi.org/10.1093/brain/awf149 Harvey, P. D., Wingo, A. P., Burdick, K. E., & Baldessarini, R. J. (2010). Cognition and disability in bipolar disorder: Lessons from schizophrenia research. Bipolar Disorders, 12, 364–375. http:// dx.doi.org/10.1111/j.1399-5618.2010.00831.x 84

Hasler, G., Drevets, W. C., Gould, T. D., Gottesman, I. I., & Manji, H. K. (2006). Toward constructing an endophenotype strategy for bipolar disorders. Biological Psychiatry, 60, 93–105. http://dx.doi.org/ 10.1016/j.biopsych.2005.11.006 Hasselbalch, B. J., Knorr, U., & Kessing, L. V. (2011). Cognitive impairment in the remitted state of unipolar depressive disorder: A systematic review. Journal of Affective Disorders, 134, 20–31. http:// dx.doi.org/10.1016/j.jad.2010.11.011 Hatch, S. L., Jones, P. B., Kuh, D., Hardy, R., Wadsworth, M. E. J., & Richards, M. (2007). Childhood cognitive ability and adult mental health in the British 1946 birth cohort. Social Science and Medicine, 64, 2285–2296. http://dx.doi.org/10.1016/ j.socscimed.2007.02.027 Hayes, J. P., Labar, K. S., McCarthy, G., Selgrade, E., Nasser, J., Dolcos, F., & Morey, R. A. (2011). Reduced hippocampal and amygdala activity predicts memory distortions for trauma reminders in combat-related PTSD. Journal of Psychiatric Research, 45, 660–669. http://dx.doi.org/10.1016/ j.jpsychires.2010.10.007 Hayes, J. P., Labar, K. S., Petty, C. M., McCarthy, G., & Morey, R. A. (2009). Alterations in the neural circuitry for emotion and attention associated with posttraumatic stress symptomatology. Psychiatry Research: Neuroimaging, 172, 7–15. http:// dx.doi.org/10.1016/j.pscychresns.2008.05.005 Hayes, J. P., Vanelzakker, M. B., & Shin, L. M. (2012). Emotion and cognition interactions in PTSD: A review of neurocognitive and neuroimaging studies. Frontiers in Integrative Neuroscience, 6, 89. http:// dx.doi.org/10.3389/fnint.2012.00089 Heaton, R. K., Baade, L. E., & Johnson, K. L. (1978). Neuropsychological test results associated with psychiatric disorders in adults. Psychological Bulletin, 85, 141–162. http://dx.doi.org/10.1037/ 0033-2909.85.1.141 Hebben, N., & Milberg, W. (2009). Essentials of neuropsychological assessment (2nd ed.). New York, NY: Wiley. Heilbronner, R. L., Sweet, J. J., Morgan, J. E., Larrabee, G. J., & Millis, S. R. (2009). American Academy of Clinical Neuropsychology Consensus Conference Statement on the neuropsychological assessment of effort, response bias, and malingering. Clinical Neuropsychologist, 23, 1093–1129. http://dx.doi.org/ 10.1080/13854040903155063 Heinrichs, R. W., & Zakzanis, K. K. (1998). Neurocognitive deficit in schizophrenia: A quantitative review of the evidence. Neuropsychology, 12, 426–445. http:// dx.doi.org/10.1037/0894-4105.12.3.426 Hendriks, S. M., Spijker, J., Licht, C. M. M., Beekman, A. T. F., Hardeveld, F., de Graaf, R., . . . Penninx,

Examination of Neurological and Neuropsychological Features in Psychopathology

B. W. J. H. (2014). Disability in anxiety disorders. Journal of Affective Disorders, 166, 227–233. http:// dx.doi.org/10.1016/j.jad.2014.05.006 Henry, J., & Crawford, J. R. (2005). A meta-analytic review of verbal fluency deficits in depression. Journal of Clinical and Experimental Neuropsychology, 27, 78–101. http://dx.doi.org/10.1080/138033990513654

Copyright American Psychological Association. Not for further distribution.

Hildebrandt, M. G., Stage, K. B., & Kragh-Soerensen, P. (2003a). Gender and depression: A study of severity and symptomatology of depressive disorders (ICD–10) in general practice. Acta Psychiatrica Scandinavica, 107, 197–202. http://dx.doi.org/10.1034/ j.1600-0447.2003.02108.x Hildebrandt, M. G., Stage, K. B., & Kragh-Soerensen, P. (2003b). Gender differences in severity, symptomatology and distribution of melancholia in major depression. Psychopathology, 36, 204–212. http://dx.doi.org/10.1159/000072791 Hoffmann, G. M., Gonze, J. C., & Mendlewicz, J. (1985). Speech pause time as a method for the evaluation of psychomotor retardation in depressive illness. British Journal of Psychiatry, 146, 535–538. http://dx.doi.org/ 10.1192/bjp.146.5.535 Hollander, E., Weiller, F., Cohen, L., Kwon, J. H., Decaria, C. M., Liebowitz, M. R., & Stein, D. J. (1996). Neurological soft signs in social phobia. Neuropsychiatry, Neuropsychology, and Behavioral Neurology, 9, 182–185. Hüfner, K., Frajo-Apor, B., & Hofer, A. (2015). Neurology issues in schizophrenia. Current Psychiatry Reports, 17, 32. http://dx.doi.org/10.1007/s11920-015-0570-4 Jenkins, M. A., Langlais, P. J., Delis, D. A., & Cohen, R. A. (2000). Attentional dysfunction associated with posttraumatic stress disorder among rape survivors. Clinical Neuropsychologist, 14, 7–12. http://dx.doi.org/ 10.1076/1385-4046(200002)14:1;1-8;FT007 Jones, I. H., & Pansa, M. (1979). Some nonverbal aspects of depression and schizophrenia occurring during the interview. Journal of Nervous and Mental Disease, 167, 402–409. http://dx.doi.org/10.1097/ 00005053-197907000-00002 Kaneko, Y., & Keshavan, M. (2012). Cognitive remediation in schizophrenia. Clinical Psychopharmacology and Neuroscience, 10, 125–135. http://dx.doi.org/10.9758/ cpn.2012.10.3.125

American Journal of Psychiatry, 159, 1427–1429. http:// dx.doi.org/10.1176/appi.ajp.159.8.1427 Kim, H. K., Nunes, P. V., Oliveira, K. C., Young, L. T., & Lafer, B. (2016). Neuropathological relationship between major depression and dementia: A hypothetical model and review. Progress in NeuroPsychopharmacology and Biological Psychiatry, 67, 51–57. http://dx.doi.org/10.1016/j.pnpbp.2016.01.008 Kiosses, D. N., & Alexopoulos, G. S. (2005). IADL functions, cognitive deficits, and severity of depression: A preliminary study. American Journal of Geriatric Psychiatry, 13, 244–249. http://dx.doi.org/ 10.1097/00019442-200503000-00010 Koenen, K. C., Moffitt, T. E., Roberts, A. L., Martin, L. T., Kubzansky, L., Harrington, H., . . . Caspi, A. (2009). Childhood IQ and adult mental disorders: A test of the cognitive reserve hypothesis. American Journal of Psychiatry, 166, 50–57. http://dx.doi.org/10.1176/ appi.ajp.2008.08030343 Koenig, A. M., DeLozier, I. J., Zmuda, M. D., Marron, M. M., Begley, A. E., Anderson, S. J., . . . Butters, M. A. (2015). Neuropsychological functioning in the acute and remitted states of late-life depression. Journal of Alzheimer’s Disease, 45, 175–185. Kolb, B., & Whishaw, I. Q. (2003). Fundamentals of human neuropsychology (5th ed.). New York, NY: Worth. Kornstein, S. G., Schatzberg, A. F., Thase, M. E., Yonkers, K. A., McCullough, J. P., Keitner, G. I., . . . Keller, M. B. (2000). Gender differences in chronic major and double depression. Journal of Affective Disorders, 60, 1–11. http://dx.doi.org/10.1016/ S0165-0327(99)00158-5 Koso, M., & Hansen, S. (2006). Executive function and memory in posttraumatic stress disorder: A study of Bosnian war veterans. European Psychiatry, 21, 167–173. http://dx.doi.org/10.1016/ j.eurpsy.2005.06.004 Krueger, R. F., & DeYoung, C. G. (2016). The RDoC initiative and the structure of psychopathology. Psychophysiology, 53, 351–354. http://dx.doi.org/ 10.1111/psyp.12551 Kurtz, M. M., & Gerraty, R. T. (2009). A meta-analytic investigation of neurocognitive deficits in bipolar illness: Profile and effects of clinical state. Neuropsychology, 23, 551–562. http://dx.doi.org/ 10.1037/a0016277

Kessler, R. C., Aguilar-Gaxiola, S., Alonso, J., Chatterji, S., Lee, S., Ormel, J., . . . Wang, P. S. (2009). The global burden of mental disorders: An update from the WHO World Mental Health (WMH) surveys. Epidemiologia e Psichiatria Sociale, 18, 23–33. http://dx.doi.org/ 10.1017/S1121189X00001421

Lai, C. H. (2011). Gray matter deficits in panic disorder: A pilot study of meta-analysis. Journal of Clinical Psychopharmacology, 31, 287–293. http://dx.doi.org/ 10.1097/JCP.0b013e31821a1045

Khan, A. A., Gardner, C. O., Prescott, C. A., & Kendler, K. S. (2002). Gender differences in the symptoms of major depression in opposite-sex dizygotic twin pairs.

Landrø, N. I., Stiles, T. C., & Sletvold, H. (2001). Neuropsychological function in nonpsychotic unipolar major depression. Neuropsychiatry, 85

Jackson and Milberg

Neuropsychology, and Behavioral Neurology, 14, 233–240. Lapierre, Y. D., & Butter, H. J. (1980). Agitated and retarded depression: A clinical psychophysiological evaluation. Neuropsychobiology, 6, 217–223. http:// dx.doi.org/10.1159/000117755

Copyright American Psychological Association. Not for further distribution.

Larrabee, G. J. (2012). Performance validity and symptom validity in neuropsychological assessment. Journal of the International Neuropsychological Society, 18, 625–630. http://dx.doi.org/10.1017/ S1355617712000240 Lee, R. S., Hermens, D. F., Porter, M. A., & RedobladoHodge, M. A. (2012). A meta-analysis of cognitive deficits in first-episode major depressive disorder. Journal of Affective Disorders, 140, 113–124. http:// dx.doi.org/10.1016/j.jad.2011.10.023 Lezak, M. D., Howieson, D. B., & Loring, D. W. (2004). Neuropsychological assessment (4th ed.). New York, NY: Oxford University Press. Liu, W. J., Yin, D. Z., Cheng, W. H., Fan, M. X., You, M. N., Men, W. W., . . . Zhang, F. (2015). Abnormal functional connectivity of the amygdala-based network in resting-state FMRI in adolescents with generalized anxiety disorder. Medical Science Monitor, 21, 459–467. http://dx.doi.org/10.12659/ MSM.893373 Livianos, L., González-Valls, P. I., García-Blanco, A. C., Tobella, H., Díaz-Alonso, I., Alberola, N., . . . Ros, L. (2015). Hypoesthesia of the malleolus as a soft sign in depression. Journal of Affective Disorders, 171, 128–131. http://dx.doi.org/10.1016/j.jad.2014.09.034 López-Larson, M. P., DelBello, M. P., Zimmerman, M. E., Schwiers, M. L., & Strakowski, S. M. (2002). Regional prefrontal gray and white matter abnormalities in bipolar disorder. Biological Psychiatry, 52, 93–100. http://dx.doi.org/10.1016/ S0006-3223(02)01350-1 MacManus, D., Laurens, K. R., Walker, E. F., Brasfield, J. L., Riaz, M., & Hodgins, S. (2012). Movement abnormalities and psychotic-like experiences in childhood: Markers of developing schizophrenia? Psychological Medicine, 42, 99–109. http://dx.doi.org/ 10.1017/S0033291711001085 Madre, M., Canales-Rodríguez, E. J., Ortiz-Gil, J., Murru, A., Torrent, C., Bramon, E., . . . Amann, B. L. (2016). Neuropsychological and neuroimaging underpinnings of schizoaffective disorder: A systematic review. Acta Psychiatrica Scandinavica, 134, 16–30. http://dx.doi.org/10.1111/acps.12564 Malhi, G. S., Ivanovski, B., Hadzi-Pavlovic, D., Mitchell, P. B., Vieta, E., & Sachdev, P. (2007). Neuropsychological deficits and functional impairment in bipolar depression, hypomania and euthymia. Bipolar Disorders, 9, 114–125. http:// dx.doi.org/10.1111/j.1399-5618.2007.00324.x 86

Mann-Wrobel, M. C., Carreno, J. T., & Dickinson, D. (2011). Meta-analysis of neuropsychological functioning in euthymic bipolar disorder: An update and investigation of moderator variables. Bipolar Disorders, 13, 334–342. http://dx.doi.org/10.1111/ j.1399-5618.2011.00935.x Martínez-Arán, A., Vieta, E., Colom, F., Torrent, C., Sánchez-Moreno, J., Reinares, M., . . . Salamero, M. (2004). Cognitive impairment in euthymic bipolar patients: Implications for clinical and functional outcome. Bipolar Disorders, 6, 224–232. http:// dx.doi.org/10.1111/j.1399-5618.2004.00111.x Martínez-Arán, A., Vieta, E., Reinares, M., Colom, F., Torrent, C., Sánchez-Moreno, J., . . . Salamero, M. (2004). Cognitive function across manic or hypomanic, depressed, and euthymic states in bipolar disorder. American Journal of Psychiatry, 161, 262–270. http://dx.doi.org/10.1176/ appi.ajp.161.2.262 Massana, G., Serra-Grabulosa, J. M., Salgado-Pineda, P., Gastó, C., Junqué, C., Massana, J., . . . Salamero, M. (2003a). Amygdalar atrophy in panic disorder patients detected by volumetric magnetic resonance imaging. NeuroImage, 19, 80–90. http://dx.doi.org/ 10.1016/S1053-8119(03)00036-3 Massana, G., Serra-Grabulosa, J. M., Salgado-Pineda, P., Gastó, C., Junqué, C., Massana, J., & Mercader, J. M. (2003b). Parahippocampal gray matter density in panic disorder: A voxel-based morphometric study. American Journal of Psychiatry, 160, 566–568. http:// dx.doi.org/10.1176/appi.ajp.160.3.566 McDermott, L. M., & Ebmeier, K. P. (2009). A metaanalysis of depression severity and cognitive function. Journal of Affective Disorders, 119, 1–8. http://dx.doi.org/10.1016/j.jad.2009.04.022 McTeague, L. M. (2016). Reconciling RDoC and DSM approaches in clinical psychophysiology and neuroscience. Psychophysiology, 53, 323–327. http:// dx.doi.org/10.1111/psyp.12602 Meyers, B. S., Mattis, S., Gabriele, M., & Kakuma, T. (1991). Effects of nortriptyline on memory selfassessment and performance in recovered elderly depressives. Psychopharmacology Bulletin, 27, 295–299. Meyers, J. E., & Meyers, K. R. (1995). Rey Complex Figure Test and Recognition trial: Professional manual. Lutz, FL: Psychological Assessment Resources. Mochcovitch, M. D., da Rocha Freire, R. C., Garcia, R. F., & Nardi, A. E. (2014). A systematic review of fMRI studies in generalized anxiety disorder: Evaluating its neural and cognitive basis. Journal of Affective Disorders, 167, 336–342. http://dx.doi.org/10.1016/j.jad.2014.06.041 Moorhead, T. W. J., McKirdy, J., Sussmann, J. E. D., Hall, J., Lawrie, S. M., Johnstone, E. C., & McIntosh, A. M. (2007). Progressive gray matter loss in patients with

Examination of Neurological and Neuropsychological Features in Psychopathology

bipolar disorder. Biological Psychiatry, 62, 894–900. http://dx.doi.org/10.1016/j.biopsych.2007.03.005

Copyright American Psychological Association. Not for further distribution.

Morey, R. A., Petty, C. M., Cooper, D. A., Labar, K. S., & McCarthy, G. (2008). Neural systems for executive and emotional processing are modulated by symptoms of posttraumatic stress disorder in Iraq War veterans. Psychiatry Research: Neuroimaging, 162, 59–72. http://dx.doi.org/10.1016/j.pscychresns. 2007.07.007 Mrad, A., Wassim Krir, M., Ajmi, I., Gaha, L., & Mechri, A. (2016). Neurological soft signs in euthymic bipolar I patients: A comparative study with healthy siblings and controls. Psychiatry Research, 236, 173–178. http://dx.doi.org/10.1016/ j.psychres.2015.11.047 Nasrallah, H. A., Tippin, J., & McCalley-Whitters, M. (1983). Neurological soft signs in manic patients: A comparison with schizophrenic and control groups. Journal of Affective Disorders, 5, 45–50. http:// dx.doi.org/10.1016/0165-0327(83)90035-6 Nebes, R. D., Pollock, B. G., Houck, P. R., Butters, M. A., Mulsant, B. H., Zmuda, M. D., & Reynolds, C. F., III. (2003). Persistence of cognitive impairment in geriatric patients following antidepressant treatment: A randomized, double-blind clinical trial with nortriptyline and paroxetine. Journal of Psychiatric Research, 37, 99–108. http://dx.doi.org/10.1016/ S0022-3956(02)00085-7 Negash, A., Kebede, D., Alem, A., Melaku, Z., Deyessa, N., Shibire, T., . . . Kullgren, G. (2004). Neurological soft signs in bipolar I disorder patients. Journal of Affective Disorders, 80, 221–230. http://dx.doi.org/ 10.1016/S0165-0327(03)00116-2 Nehra, R., Chakrabarti, S., Pradhan, B. K., & Khehra, N. (2006). Comparison of cognitive functions between first- and multi-episode bipolar affective disorders. Journal of Affective Disorders, 93, 185–192. http:// dx.doi.org/10.1016/j.jad.2006.03.013 Neu, P., Kiesslinger, U., Schlattmann, P., & Reischies, F. M. (2001). Time-related cognitive deficiency in four different types of depression. Psychiatry Research, 103, 237–247. http://dx.doi.org/10.1016/ S0165-1781(01)00286-4 Nilsonne, A. (1987). Acoustic analysis of speech variables during depression and after improvement. Acta Psychiatrica Scandinavica, 76, 235–245. http:// dx.doi.org/10.1111/j.1600-0447.1987.tb02891.x O’Toole, M. S., Pedersen, A. D., Hougaard, E., & Rosenberg, N. K. (2015). Neuropsychological test performance in social anxiety disorder. Nordic Journal of Psychiatry, 69, 444–452. Paelecke-Habermann, Y., Pohl, J., & Leplow, B. (2005). Attention and executive functions in remitted major depression patients. Journal of Affective Disorders, 89, 125–135. http://dx.doi.org/10.1016/j.jad.2005.09.006

Pannekoek, J. N., Veer, I. M., van Tol, M. J., van der Werff, S. J., Demenescu, L. R., Aleman, A., . . . van der Wee, N. J. (2013). Aberrant limbic and salience network resting-state functional connectivity in panic disorder without comorbidity. Journal of Affective Disorders, 145, 29–35. http://dx.doi.org/ 10.1016/j.jad.2012.07.006 Pissiota, A., Frans, O., Fernandez, M., von Knorring, L., Fischer, H., & Fredrikson, M. (2002). Neurofunctional correlates of posttraumatic stress disorder: A PET symptom provocation study. European Archives of Psychiatry and Clinical Neuroscience, 252, 68–75. http://dx.doi.org/10.1007/ s004060200014 Porter, R. J., Robinson, L. J., Malhi, G. S., & Gallagher, P. (2015). The neurocognitive profile of mood disorders—A review of the evidence and methodological issues. Bipolar Disorders, 17(Suppl. 2), 21–40. http://dx.doi.org/10.1111/bdi.12342 Potts, N. L., Davidson, J. R., Krishnan, K. R., & Doraiswamy, P. M. (1994). Magnetic resonance imaging in social phobia. Psychiatry Research, 52, 35–42. http://dx.doi.org/10.1016/ 0165-1781(94)90118-X Quigley, S. J., Scanlon, C., Kilmartin, L., Emsell, L., Langan, C., Hallahan, B., . . . McDonald, C. (2015). Volume and shape analysis of subcortical brain structures and ventricles in euthymic bipolar I disorder. Psychiatry Research: Neuroimaging, 233, 324–330. http://dx.doi.org/10.1016/j.pscychresns. 2015.05.012 Qureshi, S. U., Long, M. E., Bradshaw, M. R., Pyne, J. M., Magruder, K. M., Kimbrell, T., . . . Kunik, M. E. (2011). Does PTSD impair cognition beyond the effect of trauma? Journal of Neuropsychiatry and Clinical Neurosciences, 23, 16–28. http://dx.doi.org/ 10.1176/appi.neuropsych.23.1.16 Rajkowska, G., Miguel-Hidalgo, J. J., Wei, J., Dilley, G., Pittman, S. D., Meltzer, H. Y., . . . Stockmeier, C. A. (1999). Morphometric evidence for neuronal and glial prefrontal cell pathology in major depression. Biological Psychiatry, 45, 1085–1098. http://dx.doi.org/ 10.1016/S0006-3223(99)00041-4 Rauch, S. L., Shin, L. M., Segal, E., Pitman, R. K., Carson, M. A., McMullin, K., . . . Makris, N. (2003). Selectively reduced regional cortical volumes in post-traumatic stress disorder. Neuroreport, 14, 913–916. http://dx.doi.org/10.1097/ 00001756-200305230-00002 Robertson, G., & Taylor, P. J. (1985). Some cognitive correlates of affective disorders. Psychological Medicine, 15, 297–309. http://dx.doi.org/10.1017/ S0033291700023576 Robinson, L. J., & Ferrier, I. N. (2006). Evolution of cognitive impairment in bipolar disorder: A 87

Jackson and Milberg

systematic review of cross-sectional evidence. Bipolar Disorders, 8, 103–116. http://dx.doi.org/10.1111/ j.1399-5618.2006.00277.x Rohling, M. L., Green, P., Allen, L. M., III, & Iverson, G. L. (2002). Depressive symptoms and neurocognitive test scores in patients passing symptom validity tests. Archives of Clinical Neuropsychology, 17, 205–222. http://dx.doi.org/10.1093/arclin/17.3.205

Copyright American Psychological Association. Not for further distribution.

Rossi, A., De Cataldo, S., Di Michele, V., Manna, V., Ceccoli, S., Stratta, P., & Casacchia, M. (1990). Neurological soft signs in schizophrenia. British Journal of Psychiatry, 157, 735–739. http://dx.doi.org/ 10.1192/bjp.157.5.735 Rossi, A., Stratta, P., Nistico, R., Sabatini, M. D., Di Michele, V., & Casacchia, M. (1990). Visuospatial impairment in depression: A controlled ECT study. Acta Psychiatrica Scandinavica, 81, 245–249. http://dx.doi.org/ 10.1111/j.1600-0447.1990.tb06489.x Sabbe, B., Hulstijn, W., van Hoof, J., Tuynman-Qua, H. G., & Zitman, F. (1999). Retardation in depression: Assessment by means of simple motor tasks. Journal of Affective Disorders, 55, 39–44. http:// dx.doi.org/10.1016/S0165-0327(98)00087-1 Sabbe, B., Hulstijn, W., van Hoof, J., & Zitman, F. (1996). Fine motor retardation and depression. Journal of Psychiatric Research, 30, 295–306. http://dx.doi.org/ 10.1016/0022-3956(96)00014-3 Sachs, G., Anderer, P., Margreiter, N., Semlitsch, H., Saletu, B., & Katschnig, H. (2004). P300 event-related potentials and cognitive function in social phobia. Psychiatry Research: Neuroimaging, 131, 249–261. http://dx.doi.org/10.1016/j.pscychresns.2004.05.005 Sani, G., Chiapponi, C., Piras, F., Ambrosi, E., Simonetti, A., Danese, E., . . . Spalletta, G. (2016). Gray and white matter trajectories in patients with bipolar disorder. Bipolar Disorders, 18, 52–62. http:// dx.doi.org/10.1111/bdi.12359 Schrijvers, D., Hulstijn, W., & Sabbe, B. G. C. (2008). Psychomotor symptoms in depression: A diagnostic, pathophysiological and therapeutic tool. Journal of Affective Disorders, 109, 1–20. http://dx.doi.org/ 10.1016/j.jad.2007.10.019 Scott, J. C., Matt, G. E., Wrocklage, K. M., Crnich, C., Jordan, J., Southwick, S. M., . . . Schweinsburg, B. C. (2015). A quantitative meta-analysis of neurocognitive functioning in posttraumatic stress disorder. Psychological Bulletin, 141, 105–140. http://dx.doi.org/ 10.1037/a0038039

(2016). Association of neurocognition with transition to psychosis: Baseline functioning in the second phase of the North American Prodrome Longitudinal Study. JAMA Psychiatry, 73, 1239–1248. http://dx.doi.org/10.1001/ jamapsychiatry.2016.2479 Sheline, Y. I., Sanghavi, M., Mintun, M. A., & Gado, M. H. (1999). Depression duration but not age predicts hippocampal volume loss in medically healthy women with recurrent major depression. Journal of Neuroscience, 19, 5034–5043. Shin, L. M., Orr, S. P., Carson, M. A., Rauch, S. L., Macklin, M. L., Lasko, N. B., . . . Pitman, R. K. (2004). Regional cerebral blood flow in the amygdala and medial prefrontal cortex during traumatic imagery in male and female Vietnam veterans with PTSD. Archives of General Psychiatry, 61, 168–176. http://dx.doi.org/10.1001/archpsyc.61.2.168 Shin, L. M., Wright, C. I., Cannistraro, P. A., Wedig, M. M., McMullin, K., Martis, B., . . . Rauch, S. L. (2005). A functional magnetic resonance imaging study of amygdala and medial prefrontal cortex responses to overtly presented fearful faces in posttraumatic stress disorder. Archives of General Psychiatry, 62, 273–281. http://dx.doi.org/10.1001/archpsyc.62.3.273 Shin, Y. W., Dzemidzic, M., Jo, H. J., Long, Z., Medlock, C., Dydak, U., & Goddard, A. W. (2013). Increased resting-state functional connectivity between the anterior cingulate cortex and the precuneus in panic disorder: Resting-state connectivity in panic disorder. Journal of Affective Disorders, 150, 1091–1095. http:// dx.doi.org/10.1016/j.jad.2013.04.026 Snyder, H. R. (2013). Major depressive disorder is associated with broad impairments on neuropsychological measures of executive function: A meta-analysis and review. Psychological Bulletin, 139, 81–132. http://dx.doi.org/10.1037/a0028727 Sobanski, T., Wagner, G., Peikert, G., Gruhn, U., Schluttig, K., Sauer, H., & Schlösser, R. (2010). Temporal and right frontal lobe alterations in panic disorder: A quantitative volumetric and voxelbased morphometric MRI study. Psychological Medicine, 40, 1879–1886. http://dx.doi.org/10.1017/ S0033291709991930 Sobin, C., & Sackeim, H. A. (1997). Psychomotor symptoms of depression. American Journal of Psychiatry, 154, 4–17. http://dx.doi.org/10.1176/ ajp.154.1.4

Scott, J. G., & Schoenberg, M. R. (2011). Frontal lobe/ executive functioning. In M. R. Schoenberg & J. G. Scott (Eds.), The little black book of neuropsychology: A syndrome-based approach (pp. 219–248). http:// dx.doi.org/10.1007/978-0-387-76978-3_10

Sørensen, H. J., Sæbye, D., Urfer-Parnas, A., Mortensen, E. L., & Parnas, J. (2012). Premorbid intelligence and educational level in bipolar and unipolar disorders: A Danish draft board study. Journal of Affective Disorders, 136, 1188–1191. http://dx.doi.org/ 10.1016/j.jad.2011.12.007

Seidman, L. J., Shapiro, D. I., Stone, W. S., Woodberry, K. A., Ronzio, A., Cornblatt, B. A., . . . Woods, S. W.

Steen, R. G., Mull, C., McClure, R., Hamer, R. M., & Lieberman, J. A. (2006). Brain volume in first-episode

88

Examination of Neurological and Neuropsychological Features in Psychopathology

schizophrenia: Systematic review and meta-analysis of magnetic resonance imaging studies. British Journal of Psychiatry, 188, 510–518. http://dx.doi.org/10.1192/ bjp.188.6.510 Stern, Y. (2009). Cognitive reserve. Neuropsychologia, 47, 2015–2028. http://dx.doi.org/10.1016/ j.neuropsychologia.2009.03.004

Copyright American Psychological Association. Not for further distribution.

Stone, W. S., & Hsi, X. (2011). Declarative memory deficits and schizophrenia: Problems and prospects. Neurobiology of Learning and Memory, 96, 544–552. http://dx.doi.org/10.1016/j.nlm.2011.04.006 Strauss, E., Sherman, E. M. S., & Spreen, O. (2006). A compendium of neuropsychological tests: Administration, norms, and commentary (3rd ed.). New York, NY: Oxford University Press. Strawn, J. R., Wehry, A. M., Chu, W. J., Adler, C. M., Eliassen, J. C., Cerullo, M. A., . . . Delbello, M. P. (2013). Neuroanatomic abnormalities in adolescents with generalized anxiety disorder: A voxel-based morphometry study. Depression and Anxiety, 30, 842–848. http://dx.doi.org/10.1002/da.22089 Su, L., Cai, Y., Xu, Y., Dutt, A., Shi, S., & Bramon, E. (2014). Cerebral metabolism in major depressive disorder: A voxel-based meta-analysis of positron emission tomography studies. BMC Psychiatry, 14, 321. http://dx.doi.org/10.1186/s12888-014-0321-9 Substance Abuse and Mental Health Services Administration. (2014). Results from the 2013 National Survey on Drug Use and Health: Mental health findings. Retrieved from https://www. samhsa.gov/data/sites/default/files/NSDUHmhfr2013/ NSDUHmhfr2013.pdf Szabadi, E., Bradshaw, C. M., & Besson, J. A. (1976). Elongation of pause-time in speech: A simple, objective measure of motor retardation in depression. British Journal of Psychiatry, 129, 592–597. http:// dx.doi.org/10.1192/bjp.129.6.592 Thomaes, K., Dorrepaal, E., Draijer, N. P., de Ruiter, M. B., Elzinga, B. M., van Balkom, A. J., . . . Veltman, D. J. (2009). Increased activation of the left hippocampus region in complex PTSD during encoding and recognition of emotional words: A pilot study. Psychiatry Research: Neuroimaging, 171, 44–53. http://dx.doi.org/10.1016/ j.pscychresns.2008.03.003 Tolman, A. W., & Kurtz, M. M. (2012). Neurocognitive predictors of objective and subjective quality of life in individuals with schizophrenia: A meta-analytic investigation. Schizophrenia Bulletin, 38, 304–315. http://dx.doi.org/10.1093/schbul/sbq077 Trivedi, M. H., & Greer, T. L. (2014). Cognitive dysfunction in unipolar depression: Implications for treatment. Journal of Affective Disorders, 152–154, 19–27. http://dx.doi.org/10.1016/ j.jad.2013.09.012

Trotta, A., Murray, R. M., & MacCabe, J. H. (2015). Do premorbid and post-onset cognitive functioning differ between schizophrenia and bipolar disorder? A systematic review and meta-analysis. Psychological Medicine, 45, 381–394. http://dx.doi.org/10.1017/ S0033291714001512 Tsopelas, C., Stewart, R., Savva, G. M., Brayne, C., Ince, P., Thomas, A., & Matthews, F. E. (2011). Neuropathological correlates of late-life depression in older people. British Journal of Psychiatry, 198, 109–114. http://dx.doi.org/10.1192/ bjp.bp.110.078816 Van Snellenberg, J. X., Girgis, R. R., Horga, G., van de Giessen, E., Slifstein, M., Ojeil, N., . . . Abi-Dargham, A. (2016). Mechanisms of working memory impairment in schizophrenia. Biological Psychiatry, 80, 617–626. http://dx.doi.org/10.1016/j.biopsych.2016.02.017 Vasic, N., Wolf, N. D., Grön, G., Sosic-Vasic, Z., Connemann, B. J., Sambataro, F., . . . Wolf, R. C. (2015). Baseline brain perfusion and brain structure in patients with major depression: A multimodal magnetic resonance imaging study. Journal of Psychiatry and Neuroscience, 40, 412–421. http:// dx.doi.org/10.1503/jpn.140246 Vasterling, J. J., Brailey, K., Constans, J. I., & Sutker, P. B. (1998). Attention and memory dysfunction in posttraumatic stress disorder. Neuropsychology, 12, 125–133. http://dx.doi.org/10.1037/ 0894-4105.12.1.125 Vasterling, J. J., & Brewin, C. R. (2005). Neuropsychology of PTSD: Biological, cognitive, and clinical perspectives. New York, NY: Guilford Press. Vasterling, J. J., Duke, L. M., Brailey, K., Constans, J. I., Allain, A. N., Jr., & Sutker, P. B. (2002). Attention, learning, and memory performances and intellectual resources in Vietnam veterans: PTSD and no disorder comparisons. Neuropsychology, 16, 5–14. http:// dx.doi.org/10.1037/0894-4105.16.1.5 Vrabie, M., Marinescu, V., Talaşman, A., Tăutu, O., Drima, E., & Micluţia, I. (2015). Cognitive impairment in manic bipolar patients: Important, understated, significant aspects. Annals of General Psychiatry, 14, 41. http://dx.doi.org/10.1186/ s12991-015-0080-0 Wagner, S., Doering, B., Helmreich, I., Lieb, K., & Tadi´c, A. (2012). A meta-analysis of executive dysfunctions in unipolar major depressive disorder without psychotic symptoms and their changes during antidepressant treatment. Acta Psychiatrica Scandinavica, 125, 281–292. http://dx.doi.org/ 10.1111/j.1600-0447.2011.01762.x Wechsler, D. (1987). Wechsler Adult Intelligence Scale. New York, NY: Psychological Corp. Wheeler, A. L., & Voineskos, A. N. (2014). A review of structural neuroimaging in schizophrenia: From 89

Jackson and Milberg

connectivity to connectomics. Frontiers in Human Neuroscience, 8, 653. http://dx.doi.org/10.3389/ fnhum.2014.00653

Copyright American Psychological Association. Not for further distribution.

Winokur, G., Morrison, J., Clancy, J., & Crowe, R. (1973). The Iowa 500: Familial and clinical findings favor two kinds of depressive illness. Comprehensive Psychiatry, 14, 99–106. http://dx.doi.org/10.1016/ 0010-440X(73)90002-3 Wittmann, A., Schlagenhauf, F., John, T., Guhn, A., Rehbein, H., Siegmund, A., . . . Ströhle, A. (2011). A new paradigm (Westphal-Paradigm) to study the neural correlates of panic disorder with agoraphobia. European Archives of Psychiatry and Clinical Neuroscience, 261, 185–194. http://dx.doi.org/10.1007/ s00406-010-0167-1 Woodberry, K. A., Giuliano, A. J., & Seidman, L. J. (2008). Premorbid IQ in schizophrenia: A meta-analytic review. American Journal of Psychiatry, 165, 579–587. http://dx.doi.org/10.1176/appi.ajp.2008.07081242 World Health Organization. (2001). The World health report 2001—Mental health: New understanding, new hope. Geneva, Switzerland: Author.

90

Yehuda, R., Golier, J. A., Tischler, L., Stavitsky, K., & Harvey, P. D. (2005). Learning and memory in aging combat veterans with PTSD. Journal of Clinical and Experimental Neuropsychology, 27, 504–515. http:// dx.doi.org/10.1080/138033990520223 Yozawitz, A. (1986). Applied neuropsychology in a psychiatric center. In I. Grant & K. M. Adams (Eds.), Neuropsychological assessment of neuropsychiatric disorders (pp. 121–146). New York, NY: Oxford University Press. Zakzanis, K. K., Leach, L., & Kaplan, E. (1998). On the nature and pattern of neurocognitive function in major depressive disorder. Neuropsychiatry, Neuropsychology, and Behavioral Neurology, 11, 111–119. Zhao, Q., Ma, Y.-T., Lui, S. S. Y., Liu, W.-H. L., Xu, T., Yu, X., . . . Chan, R. C. K. (2013). Neurological soft signs discriminate schizophrenia from major depression but not bipolar disorder. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 43, 72–78. http://dx.doi.org/10.1016/ j.pnpbp.2012.12.006

Chapter 5

Behavioral Genetic Insights on the Development of Psychopathology

Copyright American Psychological Association. Not for further distribution.

Matt McGue, Gretchen Saunders, and Irving I. Gottesman

Behavioral genetics represents a small area within the field of psychopathology research, but it is an area that has had a large impact on how psychologists think about the origins of psychopathology. In the 20th century, behavioral genetics was focused primarily on establishing the heritable basis of psychopathology, usually with twin and adoption studies. In the 21st century, the field has shifted to trying to identify the specific genetic variants underlying heritable effects using molecular genetic approaches. In this chapter, we trace findings from twin and adoption studies through to molecular genetic investigations to characterize what is currently known about the genetics of psychopathology risk. We end the chapter with a discussion of models of gene–environment interplay. A major challenge for the field in the future will be understanding how genes and environments come together to affect the development of psychopathology. TWIN AND ADOPTION STUDIES One of the most replicated and robust observations in psychopathology research is that mental health problems aggregate in families. Indeed, dating from the founding of modern psychiatry, family history has been shown to be one of the most powerful predictors of risk for mental illness (Rosenthal, 1971). Yet familial aggregation may owe to the genes or the environments family members share. Building on the foundational work of R. A. Fisher (1919), biometrics

seeks to quantify and characterize genetic and environmental contributions to familial resemblance. To do this, biometrics depends on pivotal observations that allow investigators to investigate the separate contributions of genetic and environmental factors. This has typically involved the study of twins and adopted relatives, which have complementary strengths and weaknesses. Findings from twin and adoption studies have unequivocally documented the pervasive influence of genetic factors on psychopathology risk. These studies have also provided important insights into the nature of environmental risk.

Biometric Approaches and Heritability Psychopathology is familial, yet its transmission within families rarely follows expectations under a single-gene, Mendelian model. In the early part of the 20th century, many geneticists thought there were two alternative forms of inheritance: one that accounted for the familial transmission of single-gene characters such as those Mendel studied and a second that accounted for the inheritance of quantitative characters, such as those Galton studied. Fisher (1919) resolved the dispute by showing how Mendel’s laws of inheritance, when extended to allow for the effects of multiple alleles across multiple genetic loci, could give rise to the inheritance of quantitative phenotypes. Only one model of inheritance was needed. Biometrical genetics seeks to build on Fisher’s theoretical contributions to characterize the overall contribution of genetic and environmental factors to

Sadly, Irving I. Gottesman passed away on June 29, 2016. He was involved in the conceptualization and early drafts of the chapter but did not read the final version. http://dx.doi.org/10.1037/0000064-005 APA Handbook of Psychopathology: Vol. 1. Psychopathology: Understanding, Assessing, and Treating Adult Mental Disorders, J. N. Butcher (Editor-in-Chief) Copyright © 2018 by the American Psychological Association. All rights reserved.

APA Handbook of Psychopathology: Psychopathology: Understanding, Assessing, and Treating Adult Mental Disorders, edited by J. N. Butcher and J. M. Hooley Copyright © 2018 American Psychological Association. All rights reserved.

91

Copyright American Psychological Association. Not for further distribution.

McGue, Saunders, and Gottesman

phenotypic differences among individuals (Evans, Gillespie, & Martin, 2002). The basic biometric model assumes that the variance in a quantitative phenotype (e.g., height, neuroticism scale score, number of depression symptoms), denoted as P, can be represented as an additive combination of genetic and environmental components of variance: P = (A + D + I) + (C + E), where the three genetic components represent additive (A), dominance (D, i.e., the interaction of alleles at a single locus cumulated over multiple loci), and epistasis (I, i.e., the interaction of alleles across loci) effects, and the two environmental components represent shared (C) and nonshared environmental (E) effects. The shared environmental component represents the effects of those environmental factors that are shared by reared-together relatives (e.g., the socioeconomic status of the home, neighborhood and schools, common rearing practices of parents) and are thus the environmental basis for their phenotypic resemblance. The nonshared environmental component represents the effects of environmental factors that are not shared among relatives (e.g., unique traumatic experiences, peer group networks) and are thus the environmental basis for their phenotypic differences. The heritability of a trait is the proportion of phenotypic variance attributable to genetic factors, or h2 = (A + D + I) / P. The proportions of variance attributable to shared environmental (c2 = C / P) and nonshared environmental (e2 = E / P) factors are similarly defined. The basic properties of the heritability coefficient derive from its statistical definition as a ratio of two variances (i.e., genetic variance to total variance). By focusing on variance, heritability seeks to characterize the nature of individual differences in the population. It is important to note that attributes that do not vary in the population (e.g., humans having two eyes) would have a heritability coefficient of zero, even when these attributes have an obvious genetic basis. The heritability statistic has been a source of considerable controversy within psychology, yet it continues to be a valuable descriptive statistic within genetics, especially in the current molecular era (Visscher, Hill, & Wray, 2008). Heritability indexes the extent to which individual differences in a trait can be attributed to genetic differences among individuals. As such, it provides a 92

useful yardstick for gauging the success of efforts to identify the specific genetic variants affecting disease risk, as we discuss later in this chapter. The major concerns with heritability include that it is difficult to estimate, especially in human populations; that it is subject to misinterpretation (e.g., as an index of genetic determination); and that it is not a fixed constant but rather can vary depending on environmental circumstances (Johnson, Penke, & Spinath, 2011). Within psychology, the heritability coefficient has sometimes been misconstrued as an index of genetic determinism. A particularly notable example, described by the prominent economist Arthur Goldberger (1979), involved a twin study of income. In response to the finding that income was reported to be moderately heritable, the eminent psychologist Hans Eysenck was quoted as saying that the study “really tells the [Royal] Commission [on the Distribution of Income and Wealth] that they might as well pack up” (“Twins Show Heredity Link,” 1977, p. 337). In fact, heritability cannot tell one whether a trait is malleable; there are numerous examples of highly heritable traits that are responsive to environmental influence and intervention (Wells & Stock, 2011). Height provides a useful example. Twin studies have consistently reported heritability estimates of 80% or greater for height (Silventoinen et al., 2003). Nonetheless, North and South Koreans differ on average by about 7 centimeters in height (Schwekendiek, 2009), and the average height of an adult European man has increased by about 1 centimeter per decade throughout the 20th century (Hatton & Bray, 2010). Neither of these effects can be accounted for by genetic factors; they must be largely if not entirely due to differences in the environment. Heritability is also not a fixed biological constant. It is expected to be greater in situations in which there is little environmental variance and smaller in situations in which environmental variance is maximized. Rather than being a limitation, however, this feature of heritability can actually lead to unique insights into the nature of gene–environment interplay. A useful illustration is provided by a multicountry twin study of reading competency (Samuelsson et al., 2008). Among kindergartners, the heritability of reading achievement was estimated to be 68% in a sample of twins from Colorado

Copyright American Psychological Association. Not for further distribution.

Behavioral Genetic Insights on the Development of Psychopathology

but only 33% in a sample of Swedish twins. Reading is not emphasized in the curriculum for kindergartners in Sweden but is in Colorado. Consequently, whether Swedish kindergartners know how to read will depend heavily on experiences outside of school, experiences that are likely to differ markedly from one child to the next. In both countries, however, all first graders are exposed to a structured reading curriculum, making differential experiences outside of school less critical. In first grade, the heritability of reading was estimated to be approximately 80% in both countries. Whereas heritability refers to the proportion of variance in a quantitative trait attributable to genetic factors, many of the traits of interest to psychopathologists are discrete, for example, a diagnosis of schizophrenia, autism, or major depression. The multifactorial threshold (MFT) model provides a framework for investigating the quantitative inheritance of a discrete phenotype (van Dongen, Slagboom, Draisma, Martin, & Boomsma, 2012). In the MFT model, a discrete trait is considered to be the manifestation of an underlying continuously distributed variable, termed liability (Figure 5.1). An individual’s liability is not directly observed. Rather, what is observed is whether an individual’s liability exceeds some threshold value, which determines whether the individual is affected with the disorder. As with any quantitative phenotype, multiple genetic and environmental factors can contribute to variance in liability. When the MFT model is used to derive heritability estimates for categorical phenotypes, these estimates formally apply to the unobserved quantitative liability scale. More important, the MFT model implies that the genetic diathesis underlying psychopathology risk owes to multiple genes rather than just one gene (Gottesman & Shields, 1967). As we show later, this prediction from the MFT model has received consistent support from recent molecular genetic research.

Twin Studies of Psychopathology Logic of the twin design.  The most common behavioral genetic design involves comparison of the similarity of reared-together monozygotic (MZ) twins to the similarity of reared-together dizygotic

UNAFFECTED

AFFECTED

LIABILITY

Figure 5.1.  Multifactorial threshold model. A categorical phenotype, such as a psychiatric diagnosis, is assumed to be a manifestation of an underlying quantitative variable called liability. An individual will be affected whenever her or his combined liability score exceeds some threshold on the liability scale. As with other quantitative traits, both genetic and environmental factors can contribute to variance in liability.

(DZ) twins. MZ twins are the result of the fertilization of a single egg by a single sperm, which for some unknown reason divides into two zygotes some time within the first 10 days after conception. MZ twins have in effect inherited the same DNA sequence. In contrast, DZ twins are the result of the independent fertilization of two eggs by two sperm. Like ordinary siblings, DZ twins share on average half their segregating genetic material, but like MZ twins they are the same age and are reared together in the same home. Moreover, although DZ twin pairs can be either like-sex or unlike-sex, many studies restrict their samples to like-sex pairs to facilitate the comparison to the necessarily like-sex MZ pairs. The basic logic underlying a twin study is that if MZ twins are more similar on some trait than DZ twins, then genetic factors contribute to individual differences on that trait. The key comparisons from a twin study can be placed within a biometric framework. If one assumes that all genetic effects are additive, the 93

McGue, Saunders, and Gottesman

Copyright American Psychological Association. Not for further distribution.

expected MZ correlation (rMZ) is given by a2 + c2, where a2 is the proportion of phenotypic variance attributable to additive genetic effects (sometimes called additive heritability to distinguish it from total heritability, or h2). The expected DZ correlation (rDZ) is given by 1 / 2 a2 + c2. Simple algebraic manipulation of these two equations, along with the constraint that the total normed variance, here a2 + c2 + e2, equals 1.0, gives the Falconer estimates (more commonly called ACE estimates) that are typically reported in most twin studies: a2 = 2(rMZ − rDZ) c2 = 2rDZ − rMZ e2 = 1 − rm Variance component estimation from a twin study rests on several key assumptions. Most significantly, for heritability estimates from twin studies to be unbiased, environmental factors cannot contribute to greater MZ than DZ similarity, an assumption that has been called the equal environmental similarity assumption. Over the past 40 years, there have been numerous empirical evaluations of this assumption using a variety of methodologies (for a recent review, see Felson, 2014). In general, this literature has suggested that any bias in heritability estimates from failure to meet the equal environmental similarity assumption is likely to be small. A second key assumption is the absence of fundamental differences between twins and nontwins that would limit the generalizability of findings from twin studies. This assumption has been of special concern to psychopathologists given the early claim that the unique nature of the twin relationship places twins at elevated risk of developing mental health problems (Jackson, 1960). In fact, large registry-based studies have found little difference in the rate of mental health problems among twins versus nontwins (Kendler, Pedersen, Farahmand, & Persson, 1996), and similar minimal differences have been reported on self-report personality scales (Johnson, Krueger, Bouchard, & McGue, 2002). A final key assumption in a twin study is that all of the genetic effects are additive. The existence of nonadditive genetic variance could lead to an overestimation of heritability and a comparable underestimation of the contribution of shared 94

environmental factors. Currently, there is considerable debate among genetic epidemiologists about the theoretical and empirical evidence for the existence of nonadditive genetic factors, and the issue remains open (Carlborg & Haley, 2004; Hill, Goddard, & Visscher, 2008). The relative contribution of nonadditive genetic effects to MZ and DZ twin similarity is greater than the 2:1 relative contribution for additive effects. Consequently, one indicator of genetic nonadditivity is an MZ correlation that exceeds the corresponding DZ correlation by more than a factor of 2. A recent massive meta-analysis of more than 2,700 twin studies that reported results on more than 17,500 traits on samples that totaled more than 14 million twin pairs concluded, however, that published twin correlations provided very little evidence of nonadditivity (Polderman et al., 2015). Findings from twin studies of psychopathology.  Table 5.1 summarizes findings from either single representative twin studies of psychopathology or, when available, meta-analyses of twin studies of psychopathology. For individual studies, the table reports twin concordance rates for the disorder and, when reported, estimates of the contribution of additive genetic (a2), shared environmental (c2), and nonshared environmental (e2) contributions to liability variance. Although concordance rates and associated variance component estimates vary from disorder to disorder, several general trends are notable. First, MZ twins are consistently more concordant for psychopathology than DZ twins, implicating the importance of genetic contributions to psychopathology risk. Estimates of additive genetic heritability are generally moderate, falling in the 30% to 60% range. Second, estimates of shared environmental contributions to liability variance are uniformly small. Growing up in the same family does not appear to contribute much to the familial aggregation of mental health problems. Finally, for most disorders the estimate of the nonshared environmental contribution to liability variance is moderate to large. The environment has a substantial influence on psychopathology risk, although the relevant environmental factors appear to be those that differentiate one family member from another rather than those that they share.

— —

Meta-analysis Twin study Twin study

Hettema et al. (2001)

Kendler, Neale, Kessler, Heath, and Eaves (1992a) Kendler, Karkowski, Neale, and Prescott (2001)

Kendler, Neale, Kessler, Heath, and Twin study Eaves (1992a) Kendler, Myers, Prescott, and Neale (2001) Twin study

Meta-analysis

3

Meta-analysis

Hettema, Neale, and Kendler (2001)

Taylor (2011)

5 —

Sullivan, Neale, and Kendler (2000) Meta-analysis Kendler, Gatz, Gardner, and Pedersen (2006) Twin study

M&F

8,485 4,358 5,502

M&F M F

1,198

1,081

Agoraphobia

9,007

M F

M

F

M&F

Panic disorder

4,561 832

0.12

0.41



— —

— — —



United States United States



1,198

1,081

M

F

M&F Social phobia

22,690

0.13

0.31



Obsessive-compulsive disorder

United States



2,106

MZ

0.10

0.12



0.12

0.15



— —

— — —



0.20 0.05 0.06

DZ

concordance

Proband-wise

M & F 0.67 M & F 0.40 M & F 0.43

Schizophrenia

62 67 25

Major depression

United States





Sex

Bipolar disorder

pairs

No. of twin

Generalized anxiety disorder

— Sweden



Denmark England Finland

Country



14

3

12

Meta-analysis

Sullivan, Kendler, and Neale (2003)

— — —

study

Twin study Twin study Twin study

No. of studiesa

Type of

Bertelsen, Harvald, and Hauge (1977) McGuffin et al. (2003) Kieseppä, Partonen, Haukka, Kaprio, and Lönnqvist (2004)

Author (year)

Representative Individual and Meta-Analyses of Twin Studies of Psychopathology

Table 5.1 

95% CI

Shared

— — —

c2

95% CI

environmentb

— — —

NR

NR 0.20 [0.00, 0.41]

0.30

0.38 [0.30, 0.46]

0.37 [0.07, 0.61]

0.39

0.43 [0.32, 0.53]













0.32 [0.24, 0.39] — 0.32 [0.24, 0.39] 0.17 [0.03, 0.29]

0.37 [0.33, 0.42] 0.29 [0.19, 0.38] 0.42 [0.36, 0.47]

0.81 [0.73, 0.90] 0.11 [0.03, 0.19]

— 0.85 [0.73, 0.93] 0.93 [0.69, 1.00]

a2

Genetic

Copyright American Psychological Association. Not for further distribution.

0.80

0.70

0.52

0.63

0.61

0.57

0.68 0.51

0.63 0.71 0.58

0.08

— 0.15 0.07

e2

95

(continues)

[0.59, 1.00]

NR

[0.50, 0.55]

[0.39, 0.93]

NR

[0.47, 0.68]

[0.61, 0.76] [0.41, 0.64]

[0.58, 0.67] [0.62, 0.81] [0.53, 0.64]

NR

[0.07, 0.27] [0.00, 0.31]

95% CI

Unique environment

Behavioral Genetic Insights on the Development of Psychopathology

96 20

a

Sex

M&F

M&F M&F

8,451

M&F

Autism spectrum disorder

12,623

37,700 542

M

M&F

M F

M&F M&F

Externalizing

1,198

34,973

7,539 4,483

14,471 48,491





— —

0.41



— —

— —

MZ



M&F









— —

0.24



— —

— —

DZ

concordance

Proband-wise

Attention-deficit/hyperactivity disorder





— United States

United States



— —

— —

pairs

No. of twin

Substance use disorder

Country

95% CI c2

b

95% CI

environment

Shared

NR

NR NR



0.12 NR



NR

0.76

NR

NR

0.74 [0.70, 0.87] 0.25 [0.12, 0.37)

0.49

0.45 0.60

0.71 [0.57, 0.82]

0.52 [0.54, 0.63] 0.13 [0.06, 0.22]

0.51 [0.38, 0.65] 0.20 [0.11, 0.28] 0.59 [0.44, 0.73] 0.15 [0.01, 0.30]

0.24 [0.20, 0.26] NR 0.51 [0.45, 0.56] 0.10 [0.03, 0.16]

a2

Genetic

NR

0.01

0.51

0.43 NR

0.29

0.35

0.29 0.26

NR 0.39

e2

[0.01, 0.03)

NR

NR

[0.18, 0.43)

[0.34, 0.41)

[0.22, 0.35) [0.23, 0.30)

[0.38, 0.42)

95% CI

Unique environment

Note. a2 = additive genetic heritability; c2= shared environmental component of variance; CI = confidence interval; DZ = dizygotic; e2 = nonshared environmental component of variance; F = female; M = male; MZ = monozygotic; NR = not reported. aOnly included for meta-analyses. bDash indicates that this parameter was constrained to be zero in the best-fitting model.

Meta-analysis

Faraone et al. (2005)

7

38

Meta-analysis Meta-analysis

42 —



Twin study

Meta-analysis Twin study

10

7 6

Meta-analysis

Meta-analysis

18 12

studies

study

Meta-analysis Meta-analysis

No. of

Type of

Tick, Bolton, Happé, Rutter, and Rijsdijk (2016)

Rhee and Waldman (2002) Hicks, Krueger, Iacono, McGue, and Patrick (2004) Bezdjian, Baker, and Tuvblad (2011)

Tobacco M. D. Li, Cheng, Ma, and Swan (2003) All drugs Kendler, Myers, Prescott, and Neale (2000)

Alcohol Walters (2002) Verhulst, Neale, and Kendler (2015) Cannabis Verweij et al (2010)

Author (year)

Representative Individual and Meta-Analyses of Twin Studies of Psychopathology

Table 5.1  (Continued)

Copyright American Psychological Association. Not for further distribution.

McGue, Saunders, and Gottesman

Copyright American Psychological Association. Not for further distribution.

Behavioral Genetic Insights on the Development of Psychopathology

These three general findings from twin studies of psychopathology will be familiar to any who have followed behavioral genetic research over the past 30 years. Indeed, they have been proclaimed as the “three laws of behavioral genetics” by the behavioral geneticist Eric Turkheimer (2000). Although the magnitude of genetic contributions may vary across behavioral phenotypes, twin studies are overwhelmingly consistent in indicating that genetic factors make some contribution to phenotypic variance. Alternatively, no complex behavioral trait is genetically determined. The consistent observation that genetically identical MZ twins are never perfectly concordant for psychopathology necessarily implicates the importance of environmental influences. Surprisingly, however, given the focus of much developmental psychopathology research, the relevant environmental influences appear to be those that create differences rather than similarities among reared-together relatives (Plomin, 2011).

Adoption Studies of Psychopathology In principle, an adoption study is the most direct method for assessing the separate contributions of genetics and the shared environment to familial resemblance. An adopted individual’s genetic background is determined by birth parents with whom the adopted individual was not raised; the adopted individual’s rearing environment is largely determined by non–genetically related adoptive relatives. Consequently, resemblance of the adopted individual to birth parents would implicate the importance of genetic factors, whereas resemblance to adopted relatives would implicate the importance of (shared) environmental influences. In practice, however, many factors limit the clean separation of genetic and environmental influence in this idealized version of an adoption study. For example, adopted individuals may share critical early developmental experiences with their birth parents (obviously the case for prenatal factors), and selective placement may result in a matching of adoptive homes to birth background. Perhaps the greatest limitation to adoption research is the feasibility of identifying large and representative samples of adopted individuals and their birth and adoptive parents. As a consequence,

most adoption studies of psychopathology have been undertaken using Nordic registers in which linkages allow an investigation of a selected number of psychopathology phenotypes. Although the number of studies is limited, findings from adoption studies have generally agreed with the conclusion from twin studies that familial resemblance for psychopathology owes predominantly to genetic factors. In the classic adoption studies of schizophrenia, for example, increased risk of schizophrenia was observed in the biological but not the adoptive relatives of adopted individuals with schizophrenia (Kendler & Gruenberg, 1984; Kendler, Gruenberg, & Kinney, 1994). A similar pattern of greater risk in biological versus adoptive relatives has been observed for a wide range of psychopathological conditions including attention-deficit/ hyperactivity disorder (ADHD; Sprich, Biederman, Crawford, Mundy, & Faraone, 2000), depression (Wender et al., 1986), bipolar disorder (Mendlewicz & Rainer, 1977), drug abuse (Kendler et al., 2015), alcoholism (Verhulst, Neale, & Kendler, 2015), and antisocial personality disorder (Rhee & Waldman, 2002). Although estimates of the shared environmental contribution to psychopathology are typically small, they are not necessarily zero (Burt, 2009), and adoption studies are uniquely positioned to identify aspects of the family environment, unconfounded by genetic factors, that are associated with psychopathology risk. The familial transmission of depression provides a useful example. There is a substantial literature showing increased risk of psychopathology among the children of depressed mothers (Goodman & Gotlib, 1999). Although various hypotheses have been advanced to account for this association (e.g., maternal depression alters parenting practices; Lovejoy, Graczyk, O’Hare, & Neuman, 2000), one possibility is that it is due to genetic transmission. The observation of increased behavioral and emotional problems among the adoptive offspring of depressed mothers (McAdams et al., 2015; Tully, Iacono, & McGue, 2008), however, demonstrates that the association cannot be attributed entirely to genetic factors. In a similar way, other adoption studies have, for example, demonstrated the importance of adopted parent divorce, criminal activity, 97

McGue, Saunders, and Gottesman

and substance abuse in the etiology of drug abuse (Kendler et al., 2012) and adoptive parent marital and legal problems in offspring aggression and antisocial behavior (Cadoret, Yates, Troughton, Woodworth, & Stewart, 1995).

Copyright American Psychological Association. Not for further distribution.

Comorbidity Among Mental Health Disorders Mental health disorders do not typically occur in isolation but rather co-occur, or are comorbid, with other mental health disorders (Kessler, Chiu, Demler, Merikangas, & Walters, 2005; Kessler et al., 1994). The pervasive comorbidity that exists among mental health disorders has fueled debate over current diagnostic boundaries and discussion over how genetic methods might inform that debate (Kendler, 2006). Greater than chance levels of comorbidity between two disorders suggests some shared etiology. That is, the genetic and environmental factors affecting risk for one disorder must overlap those affecting risk for the other. The simultaneous biometric analysis of multiple psychopathological disorders can provide important insights into the nature and sources of comorbidity, even if it cannot fully resolve nosological disputes (Neale & Kendler, 1995). The relationship between depression and anxiety disorders provides a useful early example of the utility of multivariate biometric approaches. A majority of individuals with depression also have an anxiety disorder; conversely, a large number of individuals with an anxiety disorder also have depression (Hirschfeld, 2001). Using a sample of 1,003 female twins, Kendler, Neale, Kessler, Heath, and Eaves (1992b) reported that genetic factors were the predominant source of the comorbidity of depression with generalized anxiety disorder. In fact, they were unable to statistically distinguish the genetic factors underlying the two disorders (i.e., the genetic correlation between the two disorders was not significantly different from 1.0). This study, thus, suggests that depression and generalized anxiety share the same genetic liability and that which disorder an individual develops depends on the environmental factors to which that individual is exposed. This initial report by Kendler et al. (1992b) has stimulated a series of biometric investigations of large samples of twins assessed on multiple 98

indicators of mental illness. Findings from these studies have consistently supported the existence of two broad quantitative dimensions underlying risk for common mental disorders (Kendler, Prescott, Myers, & Neale, 2003). Genetic and environmental contributions to risk for any given disorder will, consequently, be a function of genetic and environmental influences on the general dimensions, which account for the comorbidities among disorders, and genetic and environmental influences that are disorder specific, which serve to differentiate the etiology of one disorder from those of the others (Figure 5.2). The first general dimension of risk is called externalizing psychopathology. High scorers on this dimension are characterized by poor impulse control, disinhibited behavior, and transgressions against social norms. In childhood, externalizing psychopathology can manifest as a disruptive disorder such as ADHD, conduct disorder, or oppositional defiant disorder. In adulthood, it can manifest as a substance use disorder or antisocial behavior. Externalizing psychopathology is also correlated with normal-range variation in personality measures of impulsivity and low behavioral control (Krueger, McGue, & Iacono, 2001). The heritability of latent externalizing psychopathology has consistently been estimated to be high in samples of children (Bornovalova, Hicks, Iacono, & McGue, 2010), adolescents (Krueger et al., 2002; Young, Stallings, Corley, Krauter, & Hewitt, 2000), and adults (Hicks, Krueger, Iacono, McGue, & Patrick, 2004). The second major dimension of inherited risk is internalizing psychopathology, characterized by the experience of psychological distress and fear. Internalizing psychopathology can manifest as depression, an anxiety disorder, or a phobia and is correlated with normal-range variation in personality measures of negative emotionality or neuroticism (Krueger et al., 2001). Biometric analyses have also found internalizing psychopathology to be heritable, albeit not as heritable as externalizing psychopathology (Blonigen, Hicks, Krueger, Patrick, & Iacono, 2005). Externalizing and internalizing psychopathology apply to risk for common mental health disorders. There is also substantial comorbidity among less common disorders, such as schizophrenia, autism, and bipolar disorder, and, as with common

Behavioral Genetic Insights on the Development of Psychopathology

DISORDER – SPECIFIC GENETIC & ENVIRONMENTAL INFLUENCES

Dysthymia

Anxious Misery

General Anxiety

Internalizing

Phobias Fear Panic Disorder

Alcohol Dependence Drug Dependence

Externalizing

GENERAL GENETIC & ENVIRONMENTAL INFLUENCES

Copyright American Psychological Association. Not for further distribution.

Depression

ASPD

Figure 5.2.  Model of externalizing and internalizing psychopathology, based on the work of Krueger (1999), Kendler, Prescott, Myers, and Neale (2003), and Vollebergh et al. (2001). The nonrandom comorbidities among ­individual psychopathological disorders is accounted for by two broad latent dimensions of vulnerability, internalizing and externalizing, which are themselves correlated. Genetic and environmental contributions to risk of ­individual disorders are either general, mediated by their effects on internalizing and externalizing psychopathology, or disorder specific. ASPD = antisocial personality disorder.

disorders, this comorbidity appears to be due largely to shared genetic influences. In a large study of the relatives of more than 35,000 individuals with schizophrenia and more than 40,000 individuals with bipolar disorder, for example, Lichtenstein et al. (2009), using the extensive Swedish registry system, reported substantial familial co-aggregation between the two disorders. The siblings of an individual with schizophrenia were 3.7 times more likely to have bipolar disorder than the siblings of controls; conversely, the siblings of someone with bipolar disorder were 3.9 times more likely to have schizophrenia than controls. Using biometric analysis, these researchers concluded that the comorbidity between schizophrenia and bipolar disorder was due predominantly to shared genetic factors; the genetic correlation between the two disorders was estimated to be .60. More generally, Smoller (2013) summarized evidence for genetic contributions to

the comorbidities among a wide range of mental health disorders, finding that in many cases genetic correlations are moderate to strong.

Developmental Considerations One consistent finding from the behavioral genetic literature on phenotypic variation in the nonpathological range is that with age the importance of genetic influences increases whereas the contribution of the shared environment declines (Bouchard, 2013). This pattern has been observed for a diverse set of traits including general cognitive ability (Haworth et al., 2010), social attitudes (Eaves et al., 1997), and religiousness (Koenig, McGue, & Iacono, 2008); it has also been observed with physical measures such as brain anatomy (Lenroot & Giedd, 2008) and height, weight, and body mass index (Dubois et al., 2012). Age differences in the biometric components of phenotypic variance are 99

Copyright American Psychological Association. Not for further distribution.

McGue, Saunders, and Gottesman

thought be the result of two separate developmental processes. First, the declining contribution of the shared environment is hypothesized to arise because the influence of the family environment, and especially parents, diminishes as individuals pass from childhood through adolescence into early adulthood. Alternatively, the increase in genetic influences appears to be a consequence of genetic effects being amplified over time (Briley & Tucker-Drob, 2013; Ludeke, Johnson, McGue, & Iacono, 2013). That is, although the relevant genetic factors appear to be largely the same across development, the effect of these factors increases with age. This amplification of genetic effects has been hypothesized to be a consequence of active gene–environment correlational processes: With age, individuals gain increasing control over the environments they experience, and they often exert that control by selecting environments that complement underlying genetic tendencies and consequently amplify their effects (Scarr & McCartney, 1983). The consistent observation of age differences in the biometric components of variance underlying individual differences in nonpathological phenotypes raises the question as to whether a similar pattern is observed with mental health problems. The changing nature of mental health problems across development, necessitating different assessments at different ages, makes this question difficult to answer. Nonetheless, the data that do exist suggest that mental health problems show developmental trends similar to those seen with nonpathological phenotypes. In a meta-analysis of twin studies focused on adolescence and early adulthood, Bergen, Gardner, and Kendler (2007) reported that heritability estimates increased significantly with age for externalizing psychopathology, anxiety symptoms, and depression symptoms and increased (albeit not significantly) for alcohol consumption. Estimates of the shared environmental component of variance across development were not reported in this meta-analysis but have been reported in individual studies. In a retrospective study of cigarette, alcohol, and cannabis use in a large sample of middle-aged twins, for example, Kendler, Schmitt, Aggen, and Prescott (2008) reported that estimates of shared environmental influence were approximately 50% 100

in early adolescence but declined to near zero by middle age. Heritability estimates for the three substance use phenotypes showed the opposite pattern, increasing from near zero in early adolescence to approximately 50% in mid-life. A similar pattern of decreasing shared environmental influence and increasing heritability has been observed in longitudinal twin studies of substance use (Derringer, Krueger, Iacono, & McGue, 2010; Rose, Dick, Viken, & Kaprio, 2001), although the age ranges spanned by these studies are narrower than those in the retrospective report by Kendler et al. (2008). IDENTIFYING THE SPECIFIC GENETIC FACTORS UNDERLYING HERITABLE EFFECTS ON PSYCHOPATHOLOGY Heritability estimates from twin studies imply that individuals inherit differences in their DNA sequences that affect their risk of developing psychopathology. Identifying what those differences are could help illuminate disease biology, potentially leading to more effective interventions, and help identify at-risk individuals, making targeted prevention feasible. Identifying the specific genetic factors underlying mental health problems has, however, been much more difficult than was anticipated at the outset of the Human Genome Project. Early efforts to identify genetic risk factors using the candidate gene approach had a poor record of replication. Fortunately, beginning in 2005, genome-wide association studies (GWASs) have been successful in identifying genetic associations, although the effects they have uncovered have been characteristically small in magnitude, and the vast majority of the heritability of psychopathology remains unaccounted for or missing (Gratten, Wray, Keller, & Visscher, 2014). A major focus of current research is identifying the sources of missing heritability.

Challenge of Finding the Genetic Variants Underlying Risk for Complex Phenotypes To understand the challenges inherent in identifying the specific genetic factors underlying psychopathology risk, it is helpful to consider how genetic risk for psychiatric disease is likely to be structured. Some human diseases are transmitted in

Copyright American Psychological Association. Not for further distribution.

Behavioral Genetic Insights on the Development of Psychopathology

a Mendelian fashion, in which risk is determined by the alleles inherited at a single genetic locus. This is the case for phenylketonuria, which is an autosomal recessive disorder, as well as for Huntington’s disease, which is autosomal dominant. Such diseases are called single-gene disorders because risk is determined by variants or alleles within a single gene. The Human Genome Project has been very successful in identifying the genetic variants underlying single-gene disorders (Glazier, Nadeau, & Aitman, 2002). In contrast, multifactorial disorders are complex, the result of the combined effect of multiple genetic and multiple environmental factors. Their intergenerational transmission does not conform to classical Mendelian ratios. Most common human genetic disorders, including psychopathology, are considered to be multifactorial, and identifying the relevant genetic variants is much more challenging with multifactorial diseases than with single-gene disorders. Two features of multifactorial disorders contribute to this challenge. First, for classical Mendelian disorders, inheritance of the risk genotype is typically sufficient for developing the disease in the absence of intervention. In contrast, with multifactorial disorders there is typically environmental modulation of genetic risk. The fundamental role of environmental influences in multifactorial disorders is evident in MZ twin concordance rates for psychopathology, which are typically substantially less than 100%, as is evident in Table 5.1. Second, genetic risk is attributable to a single gene of large effect for Mendelian disorders but to multiple genes for multifactorial disorders. Thus, and as we show, many genetic variants likely affect risk for each form of psychopathology, and the effect of any single variant on disease risk is likely to be very small and thus difficult to detect unless the sample is very large.

Candidate Gene Approach In the early stages of the Human Genome Project, the most common approach to identifying the genetic variants associated with psychopathology risk was a candidate gene study (Kwon & Goate, 2000). In principle, a candidate gene study involves the execution of a relatively simple research design. Investigators begin by targeting a specific gene or

set of genes on the basis of what is known about the biology of the disorder and genotyping one or more genetic variants in each targeted gene. If the phenotype is categorical (e.g., a diagnosis), then the frequencies of these variants would be compared in a sample of cases versus controls. If the phenotype is continuous (e.g., a count of symptoms), then variant status (usually summarized as a count of one of the alleles) would be correlated with the quantitative trait. In either case, the finding of a significant association would be taken as evidence that genetic variation in the candidate gene contributes to individual differences on the phenotype. There have been hundreds, perhaps thousands of candidate gene studies in psychology and psychiatry (Munafò & Flint, 2004). Despite the popularity of the candidate gene approach in human genetics, there have been concerns about the robustness of findings from these studies. In 2002, Hirschhorn, Lohmueller, Byrne, and Hirschhorn (2002) surveyed the fate of genetic associations reported in the literature for both behavioral and nonbehavioral disorders. Of the 600 significant genetic associations they identified, there was sufficient information (i.e., at least three subsequent studies) to judge the replicability of 166. Only six of the 166 reported associations were consistently replicated. Many factors have contributed to the poor replicability of candidate gene associations (Ioannidis, Ntzani, Trikalinos, & Contopoulos-Ioannidis, 2001). Foremost among these are small sample size and publication bias. The first generation of candidate gene studies were designed to have adequate statistical power for effects much larger than is now known to be the norm (see the section “Genome-Wide Association Studies” later in this chapter). Underpowered studies that achieve statistical significance are likely to overestimate the magnitude of effect and those unable to achieve statistical significance are unlikely to be published. Consequently, published studies are likely to substantially overestimate the magnitude of the effect, a phenomenon known as the “winner’s curse” (Xiao & Boehnke, 2009). To correct for this bias, there has been a call for larger studies, rigorous thresholds before an effect can be declared a discovery, and the pooling of studies using meta-analytic techniques. 101

Copyright American Psychological Association. Not for further distribution.

McGue, Saunders, and Gottesman

Another limitation of existing genetic association studies is that they have been based overwhelmingly on samples of individuals of European ancestry (Bustamante, Burchard, & De la Vega, 2011). Control for ancestral (often called racial) background is necessary in genetic association studies because of the phenomenon geneticists call population stratification. Human populations differ in the prevalence of many diseases (Breslau et al., 2006) and, because of their differing evolutionary histories, they also differ in the frequency of many genetic variants (Barbujani, Ghirotto, & Tassi, 2013). Consequently, genetic variants that vary by population will artifactually be associated with disease risk unless population structure is controlled for in the analysis (Colhoun, McKeigue, & Davey Smith, 2003). Although there are multiple ways to address the problem of population stratification, most involve at a minimum limiting analysis to one large ancestral group (e.g., Europeans, East Asians, sub-Saharan Africans). The result has been a Eurocentric bias in existing genetic association studies that is only now being addressed through calls to increase sample diversity (Bustamante et al., 2011). A further limitation of early candidate gene research in psychopathology was the relatively small number of genes that were investigated. Thousands of genes are expressed in the human brain, variation in any one of which might affect behavior. Nonetheless, until recently only a relatively small number of genes were the focus of candidate gene research. These were genes, sometimes called the “usual suspects” (Collier & Sham, 1998), for which there were genetic polymorphisms that could be genotyped and so investigated. Even though the number of targeted genes may have been limited, the candidate gene literature on psychopathology is voluminous and well beyond what we can reasonably summarize here. A recent review of candidate gene studies for major mental illness, for example, identified more than 1,500 separate meta-analyses (Gatt, Burton, Williams, & Schofield, 2015). Rather than try and review this vast literature, we have elected to highlight the candidate gene approach in psychopathology through four illustrative examples. 102

Genetic variation in the serotonin transporter and depression-related phenotypes.  The most widely studied genetic variant in the behavioral sciences is a polymorphism in the gene that codes for the serotonin transporter. The serotonin transporter binds free serotonin in the synaptic cleft and returns it to the presynaptic neuron. Multiple lines of evidence have implicated it as playing a role in psychiatric illness, especially depression (Spies, Knudsen, Lanzenberger, & Kasper, 2015). A major pharmacological treatment for depression, selective serotonin reuptake inhibitors, is thought to exert clinical efficacy by blocking the serotonin transporter, thus increasing the availability of serotonin in the synaptic cleft. The gene that codes for the serotonin transporter is known as SLC6A4, and a polymorphism in the promoter region of this gene, known as the serotonin transporter gene-linked promoter region, or 5-HTTLPR, polymorphism, is associated with different levels of gene expression. The polymorphism involves the presence (designated the long or l allele) or absence (the short or s allele) of 40 to 46 DNA bases, with the s allele being associated with lower levels of gene expression and thus less production of the serotonin transporter product. The first published study on the behavioral correlates of 5-HTTLPR reported that those who carried at least one s allele scored approximately one third standard deviation higher on a personality measure of neuroticism than those who were homozygous for the l allele (Lesch et al., 1996). In this study, the 5-HTTLPR variant was estimated to account for approximately 3% of the variance in neuroticism. Rapidly following this initial publication was a report of the s allele’s being associated with increased risk of depression (Collier et al., 1996). After these initial promising results, a perplexing series of both successful and unsuccessful reports of associations of 5-HTTLPR with both neuroticism (Ball et al., 1997; Ebstein et al., 1997) and depression (Furlong et al., 1998) ensued. However, statistical significance may not be a good way to judge replicability, especially when replication attempts are underpowered. To make sense of the complex pattern of candidate gene association findings, genetics researchers have turned to meta-analysis (Munafò & Flint, 2004).

Copyright American Psychological Association. Not for further distribution.

Behavioral Genetic Insights on the Development of Psychopathology

H. Clarke et al. (2010) undertook a meta-analysis of the association of 5-HTTLPR with depression. Pooling results across 46 separate case–control samples, they reported a pooled odds ratio (OR) associated with each s allele of 1.08. Although this OR was statistically significant, it is substantially smaller than the OR of 1.28 reported in the initial study (Collier et al., 1996), an indication that the winner’s curse phenomenon is at play. Interestingly, H. Clarke et al. also determined that a case–control study would require a total sample size of 5, 600 to have statistical power of at least 80% to detect an OR of this magnitude. None of the 46 samples they included in their meta-analysis even approached this sample size. A meta-analysis of 28 separate samples investigating the association of 5-HTTLPR with self-reported neuroticism came to similar conclusions (Munafò et al., 2009). The pooled standardized mean difference between carriers of the s allele versus ll homozygotes (d = 0.07) was statistically significant but again much smaller than the effect reported in the original study (d = 0.33). It has been hypothesized that the association of 5-HTTLPR with depression- and anxiety-related traits may be a consequence of its effect on amygdala function. The amygdala has a primary role in the processing and storage of emotional memories, and MRI studies have reported that individuals with depression or anxiety show increased amygdala activation in response to threatening stimuli. Hariri et al. (2002) investigated right amygdala response to a fearful face in a sample of 14 carriers of the s allele and 14 ll homozygotes. Mean response was significantly higher among carriers of the s allele with a standardized mean difference of d = 3.75. A statistically significant result in a small sample is precisely the circumstance likely to result in an overestimation of effect, so it is critical that the replicability of the original result be evaluated. Munafò, Brown, and Hariri (2008) meta-analyzed findings from 14 studies investigating the association of right amygdala function and 5-HTTLPR. They reported a pooled standardized mean difference of d = .63 between s carriers versus ll homozygotes, which although statistically significant was clearly substantially lower than the originally reported standardized mean difference of d = 3.75. A subsequent

meta-analysis reported an even smaller pooled standardized estimate of d = 0.21 in 34 samples, which was borderline statistically significant (Murphy et al., 2013). It is important to note that Murphy et al. (2013) reported results suggesting publication bias in this area. For example, the pooled standardized mean difference was d = 0.35 in 29 published studies but d = −0.66 in unpublished studies, and the published studies had an excess of statistically significant results relative to what would be expected given the statistical power of those studies. The literature on the 5-HTTLPR polymorphism serves to highlight the difficulties with candidate gene studies in psychiatry and behavioral genetics. The functional nature of the polymorphism makes it a strong candidate for various psychopathological conditions, and interest in this polymorphism was further encouraged by initial results that reported strong associations with a range of relevant outcomes. However, as evidence has accumulated, the strength of these associations, as reflected in metaanalyses, has diminished. Given the totality of evidence, we cannot rule out associations of 5-HTTLPR with depression and related phenotypes, although we can say that the strength of any association must be far weaker than suggested in the initial reports. Some have suggested that genotype–environment interactions may have contributed to the inconsistency of findings with 5-HTTLPR, a possibility we return to later in the chapter. Dopamine D2 receptor and addiction.  Activation of the dopamine system is a primary pathway by which drugs of abuse are experienced as positively reinforcing (Koob & Le Moal, 2001). Consequently, genetic variation in dopamine system genes, and especially the dopamine D2 receptor (DRD2), have received considerable attention by addictions researchers. In an initial investigation of the importance of DRD2 in addictions, Blum et al. (1990) reported that 69% of 35 individuals with alcoholism but only 20% of 35 control individuals carried the A1 allele in the Taq1A polymorphism in DRD2. The OR for the association was 8.7, a very large effect. Nonetheless, as with other initial reports of a genetic association in a small sample, the initial publication by Blum et al. was followed by a series 103

Copyright American Psychological Association. Not for further distribution.

McGue, Saunders, and Gottesman

of both positive replications and failures to replicate, leading some to conclude that the association was likely not real (Gelernter et al., 1991). As evidence has accumulated, however, systematic reviews of the DRD2–alcoholism literature have concluded in favor of the existence of a modest association. The most recent of these meta-analyses combined findings from 61 separate studies and reported a statistically significant pooled OR of 1.19 between the Taq1A polymorphism and alcoholism (Wang, Simen, Arias, Lu, & Zhang, 2013). Moreover, a sufficient number of samples allowed these investigators to show that the strength of the association did not differ between individuals of East Asian (pooled OR of 1.17 in 15 samples) and European (pooled OR of 1.16 in 34 samples) ancestry. Consequently, there does appear to be an association between the Taq1A polymorphism and alcoholism risk, although clearly the strength of this association is considerably weaker than what was reported in the initial report. The association of the Taq1A polymorphism with alcoholism highlights another major challenge in genetic association analysis: Determining the causal basis for a specific genetic association can be difficult. Although the Taq1A polymorphism was initially characterized as a DRD2 variant, it actually changes the protein-coding sequence of a nearby gene on chromosome 11q, ankyrin repeat and kinase domain containing-1 (ANKK1), which is involved in dopamine synthesis (Gorwood et al., 2012). Thus, the association may have nothing to do with DRD2 but rather may arise because the altered ANKK1 protein increases the risk of alcoholism. Alternatively, alleles at physically proximal loci will be correlated (a phenomenon geneticists call linkage disequilibrium, which we return to later), so that the association with the ANKK1 variant may arise because it is correlated with a nearby causal variant in the DRD2 locus. Finally, perhaps the association with alcoholism may arise because the Taq1A polymorphism regulates the expression of the nearby DRD2 gene, perhaps by altering the protein sequence in ANKK1. In any case, even when a positive genetic association can be confirmed, it can be very difficult to determine why the association arises. This is especially true when the magnitude of the association is small, which we now know to be the norm. 104

Another issue raised by research in this area concerns whether the Taq1A polymorphism is a specific risk factor for alcoholism or conveys general risk for substance abuse or externalizing psychopathology. A meta-analysis of nine studies of opiate dependence reported a statistically significant pooled OR of 1.09 for the Taq1A polymorphism, supporting the hypothesis that it is a general marker of risk (Gorwood et al., 2012). However, the same investigators did not find a significant association in their meta-analysis of 10 studies of stimulant dependence (pooled OR of 1.00) and, although they did find a significant association in 23 studies of nicotine dependence, the direction of effect was opposite to that reported for the other substance use disorders (pooled OR of 0.92; Gorwood et al., 2012). The only non–substance abuse indicator of externalizing psychopathology for which there are a sufficient number of studies to justify a meta-analytic review is ADHD. Pan, Qiao, Xue, and Fu (2015) meta-analyzed 11 association studies of the Taq1A polymorphism and ADHD and concluded that there was a significant association (pooled OR of 1.79). However, there is considerable heterogeneity in the reported results, with a single study reporting an extreme outlier OR of 7.50 (Kopecková et al., 2008). Whether the Taq1A polymorphism is associated with general substance abuse or externalizing risk remains an open question. Alcohol-metabolizing variants and ­alcoholism.  The primary metabolic pathway for the elimination of ethanol is the liver (Edenberg, 2007; Figure 5.3). Ethanol is first converted to acetaldehyde by the enzyme alcohol dehydrogenase (ADH), and acetaldehyde is then converted to acetate by the enzyme aldehyde dehydrogenase (ALDH). Multiple genes code for the alternative forms of the ADH and ALDH enzymes. Acetaldehyde is a highly toxic substance, and many of the dysphoric physiological effects of drinking, including nausea, headaches, and dizziness, are associated with high levels of acetaldehyde. Consequently, genetic variants in ADH that code for the rapid conversion of ethanol to acetaldehyde or genetic variants in ALDH that code for the slow conversion of acetaldehyde to acetate would be

Behavioral Genetic Insights on the Development of Psychopathology

ETHANOL

ACETATE

ACETALDEHYDE ADH (ADH1B ADH1C)

ALDH (ALDH2)

Copyright American Psychological Association. Not for further distribution.

Figure 5.3.  Metabolism of ethanol. The primary pathway for the elimination of ethanol is in the liver, where ethanol is converted to acetaldehyde, which is in turn converted to acetate. The enzyme involved in the first step is called alcohol dehydrogenase (ADH); the enzyme involved in the second step is called aldehyde dehydrogenase (ALDH). Multiple genes code for each enzyme; the ones most prominently linked to drinking behavior are listed parenthetically.

expected to be protective against heavy drinking and alcohol dependence (Macgregor et al., 2009). Because the conversion of acetaldehyde to acetate is the rate-limiting step in ethanol metabolism, genetic variation in ALDH might be expected to have the strongest effect on drinking behavior. A genetic variant in the gene that codes for the mitochondrial form of ALDH, known as ALDH2, has been shown to be protective against heavy drinking and alcoholism. This variant (designated the ALDH2*2 allele) results in a change in the coding sequence of the gene and results in a deficient form of the ALDH enzyme with greatly reduced capacity to convert acetaldehyde to acetate. The ALDH2*2 variant is relatively common in East Asian samples but very rare or nonexistent in other world populations (H. Li et al., 2009). As expected, the ALDH2*2 variant is associated with markedly lower rates of heavy drinking and alcoholism (Luczak, Glatt, & Wall, 2006). Although the nature of the association between ALDH2*2 and drinking seems relatively straightforward—the inability to metabolize the toxic substance acetaldehyde will discourage heavy drinking—the strength of the association has been found to be moderated by several contextual factors. For example, the strength of the protective effect of the ALDH2*2 allele has diminished over time in Japan as that society has become more tolerant of drinking (Higuchi et al., 1994). Moreover, the ALDH2*2 allele appears to have little protective effect among adolescents, perhaps because adolescent drinking is strongly driven by peer group pressure (Irons, Iacono, Oetting, & McGue, 2012). Thus, environmental modulation of genetic

influence is evident even when the nature of that influence appears to be relatively direct. Rapid conversion of ethanol to acetaldehyde by the ADH enzyme would also be expected to protect against heavy drinking, although to a lesser degree than with ALDH2. Seven genes code for different versions of the ADH enzyme. Genetic variation in two of these, ADH1B and ADH1C, has been associated with drinking behavior (Edenberg, 2007). A genetic variant in ADH1B that is associated with rapid oxidation of ethanol (designated the ADH1B*2 allele) has been shown to be protective against alcoholism. This variant is common in East Asian populations, somewhat less common in Ashkenazi Jewish populations, and rare among Africans and Europeans (Hasin et al., 2002; Whitfield, 2002). The ADH1C*1 allele shows a modest protective effect against heavy drinking and is also most common in East Asian populations (Edenberg, 2007). Dopamine system genes and attention-deficit/ hyperactivity disorder.  Disruption in the dopamine system has long been hypothesized to contribute to risk for ADHD (Wender, 1973). The fronto-subcortical regions (striatum) thought to be impaired in ADHD are rich in dopamine pathways, and pharmacological treatments for ADHD have their therapeutic effect by increasing the availability of dopamine at the synaptic cleft (Biederman & Faraone, 2005). The strong presumption that dopamine is involved in ADHD has motivated systematic genetic investigation of genes known to influence dopamine neurotransmission, including dopamine receptors (DRD1, DRD2, DRD3, DRD4, and DRD5); proteins involved either in the synthesis (e.g., dihydroxyphenylalanine) or the degradation (e.g., catechol-O-methyltransferase [COMT], monoamine oxidase A) of dopamine; and the dopamine transporter (DAT1; Gizer, Ficks, & Waldman, 2009). Because methylphenidate, the standard pharmacological treatment for ADHD, has its clinical effect by blocking DAT1, the first candidate gene to be investigated in ADHD was the gene (SLC6A3) that codes for DAT1. Two small early studies reported significant associations of ADHD with a variant in the noncoding region of SLC6A3 (Cook et al., 1995; Gill, Daly, Heron, Hawi, & Fitzgerald, 1997). This 105

Copyright American Psychological Association. Not for further distribution.

McGue, Saunders, and Gottesman

variant is known as a variable number of tandem repeats (VNTR) polymorphism because it involves a block of DNA bases (in this case, 40) repeated in tandem with the number of repeats varying among individuals in the population (most alleles are either 10 repeats or nine repeats). Both studies reported that the 10-repeat allele, which is very common in the population (e.g., with a frequency of approximately 70% among Europeans; Kang, Palmatier, & Kidd, 1999), was significantly and moderately (OR = ∼ 2.0) associated with increased risk of ADHD. Because the variant is not in the coding region of the gene, the association is thought to arise because either the VNTR variant influences how SLC6A3 is transcribed or it is correlated with another variant in the SLC6A3 gene that affects transcription. Although the two initial positive reports were encouraging, not every subsequent replication was positive (e.g., Lunetta, Faraone, Biederman, & Laird, 2000), underscoring the need for a systematic analysis of the cumulative record. Gizer et al. (2009) meta-analyzed 34 studies of SLC6A3 and ADHD and reported a modest but statistically significant association (pooled OR = 1.10), with the common 10-repeat allele being associated with increased risk. The second most frequently studied dopamine system gene in ADHD is the gene that codes for the dopamine D4 receptor (DRD4). The regions of the brain thought to be affected in ADHD are rich in DRD4s (Faraone & Biederman, 1998), and early candidate gene studies reported an association between DRD4 and the personality trait of novelty seeking (Benjamin et al., 1996; Ebstein et al., 1996), although the robustness of that association has been questioned by subsequent meta-analytic results (Munafò, Yalcin, Willis-Owen, & Flint, 2008). The main polymorphism investigated in DRD4 is a 48-base VNTR in the coding region of the gene. The number of the repeats of this block can vary anywhere from two to 11, although the most common alleles are the four-repeat and seven-repeat alleles, with the latter being the allele found initially to be associated with novelty seeking. Gizer et al. (2009) meta-analyzed 26 studies of this polymorphism in ADHD, reporting a statistically significant but moderate pooled OR of 1.27, with the seven-repeat allele being the risk allele. Gizer et al. also meta-analyzed 106

studies of other dopamine system genes, reporting a modest but significant pooled OR of 1.22 for DRD5 but nonsignificant effects for DRD2, DRD3, and COMT. As we noted previously, however, an updated meta-analysis of DRD2 and ADHD (Pan et al., 2015) did report a significant pooled OR of 1.79, although marked between-study heterogeneity suggests that caution is warranted when interpreting this result. Given that ADHD appears to be associated with multiple dopamine system genes, the question arises as to how the separate variants combine to affect ADHD risk. There is some evidence that DAT1 is associated primarily with the hyperactive–impulsive symptoms of ADHD (Mill et al., 2005; Waldman et al., 1998), whereas is DRD4 is associated primarily with symptoms of inattention (Lasky-Su et al., 2008; McCracken et al., 2000; Rowe et al., 1998). This dissociation has even been seen in laboratory studies. For example, Gizer and Waldman (2012) investigated performance on a continuous performance task and reported that DAT1 was associated with commission errors (an indicator of impulsivity) but not with omission errors (an indicator of inattention), whereas DRD4 showed the opposite pattern of association. Nonetheless, there are studies that have not found this differential association of DAT1 and DRD4 with subtypes of ADHD symptoms (Bidwell et al., 2011), suggesting that the issue is not resolved. Conclusions on candidate gene studies.  Our review of the candidate gene literature was limited to four cases, selected to illustrate limitations in even the successful applications of this approach. Nonetheless, several general conclusions are warranted. The standard candidate gene approach, whereby an investigator targets one or more genes on the basis of what is known about the biology of the phenotype, has had an inconsistent record in producing replicable associations. This problem is not specific to behavioral phenotypes, because a similar pattern of inconsistent results has been reported in candidate gene studies of nonbehavioral phenotypes. In cases in which replicable candidate gene associations have been documented through meta-analysis, the pooled effect size is typically far

Behavioral Genetic Insights on the Development of Psychopathology

smaller than the effect size reported in the initial report (i.e., the winner’s curse), and there are both positive reports as well as studies that fail to replicate the association. Caution is needed in interpreting the results of any single candidate gene study. Conclusions should be based on meta-analyses that have a sufficient number of studies to judge the replicability of results and whether there is evidence of publication bias.

Copyright American Psychological Association. Not for further distribution.

Genome-Wide Association Studies By 2005, advances in genotyping technology enabled a new, hypothesis-free approach for identifying the genetic variants underlying inherited risk. Rather than target a particular candidate gene or genomic location, in a GWAS the entire genome is surveyed to find the genetic variants underlying disease (Visscher, Brown, McCarthy, & Yang, 2012). In a GWAS, a large number of single nucleotide polymorphisms, or SNPs—at a minimum several hundred thousand but more typically one million or more—are tested for association with the target phenotype. A SNP refers to location in the genome where individuals differ in the DNA base they have inherited. Although each SNP could have up to four different alleles, that is, the G, C, T, and A nucleotide bases that make up DNA, the overwhelming majority of people in the population will usually have one of only two of the bases. It is the biallelic nature of SNPs that has made it relatively easy to efficiently genotype a large number of them. In principal, any of the 3.2 billion bases in the human genome could vary in the population. Practically, most of these variants would be rare or private, carried by a relatively small number of individuals in the world. Rather than try and survey every possible genetic variant, a GWAS focuses on the several million SNPs that are common (the definition geneticists use is that the least frequently occurring of the two alleles has a frequency of at least 1% in the population) and thus likely to be represented in any large sample. Moreover, because the SNPs are distributed throughout the genome, it is not necessary that every potential SNP be genotyped. Common SNPs that are located close to one another (i.e., on the order of thousands of bases) are likely to be highly correlated, a phenomenon

geneticists call linkage disequilibrium. Consequently, a half million or more SNPs distributed across the genome ensures that most common SNP variation is captured in a GWAS either directly through genotyping or indirectly through linkage disequilibrium. A GWAS is in some ways misleadingly simple. In a case–control GWAS, the frequency of the least frequently occurring (or minor) allele for each SNP is statistically compared in the two samples, and this test is repeated for each genotyped SNP. For a quantitative phenotype, the analysis would involve repeatedly regressing the outcome on each SNP (summarized by a count, 0–1–2, usually of the minor allele). In either case, the large number of computed statistical tests requires some correction for multiple testing to protect against false-positive results (e.g., by chance one would expect that 5%, or 50,000, tests of one million true null hypotheses to be statistically significant at the .05 level). The standard threshold for declaring a discovery in a GWAS is p < 5*10−8, which has various justifications, including that it corresponds to a Bonferroni correction of a .05 p-value threshold based on one million independent tests. In addition, most GWASs will involve some correction for population structure, because ethnic group differences in the frequencies of SNPs coupled with their phenotypic differences could easily result in artifactual associations (Cardon & Palmer, 2003). In interpreting GWAS findings, it is helpful to understand that the design of GWASs is based on a particular model of disease called the common disease–common variant (CDCV) model (Reich & Lander, 2001). Unlike Mendelian diseases such as Huntington’s disease or cystic fibrosis, which are rare, mental health disorders are considered to be common heritable disorders. How, though, can a disorder be both heritable and common if it is associated with markedly reduced fertility (e.g., people with schizophrenia reproduce at 50% or less the rate of people without schizophrenia)? Under the CDCV model, the genetic variants underlying disease are common in the population but are only weakly associated with risk. Individuals who develop schizophrenia, for example, are expected to carry a large number of these weak-effect risk alleles, but so too 107

Copyright American Psychological Association. Not for further distribution.

McGue, Saunders, and Gottesman

will individuals who have not developed schizophrenia, albeit at a slightly lower frequency than individuals with schizophrenia. Consequently, most of the schizophrenia risk alleles in the population are carried by individuals who do not have schizophrenia and so do not have a selective disadvantage. In short, the CDCV model hypothesizes that disorders such as schizophrenia are the cumulative result of many weakly associated genetic variants that are common in the population. To be adequately powered to detect variants of small effect with a very low p-value threshold requires samples that are much larger than a single investigator could hope to collect. Indeed, the experience of the first 10 years of GWAS has indicated that very little is discovered unless the number of cases exceeds 10,000 in a case–control analysis (Gratten et al., 2014). It is for this reason that various consortia have been established, including the Psychiatric Genetics Consortium (Sullivan, 2010). The progression of GWAS for schizophrenia from this consortium provides a helpful illustration of the importance of large samples. The first large-scale GWAS of schizophrenia was published in 2009 and involved a sample of more than 3,000 individuals with schizophrenia and more than 3,500 controls, and yet it yielded no significant genetic associations among the approximately one million genotyped markers tested (Purcell et al., 2009). In 2013, the sample of cases had increased to more than 21,000 and controls to more than 38,000, and 22 significant genetic associations had been found (Ripke et al., 2013). By 2014, the sample included more than 38,000 cases and more than 100,000 controls, and 108 significant genetic associations were reported (Schizophrenia Working Group of the Psychiatric Genomics Consortium, 2014). Table 5.2 summarizes findings from large-scale GWASs of selected psychiatric phenotypes as well as four quantitative behavioral traits that are associated with mental health problems. Except for schizophrenia, few other psychiatric disorders have amassed a GWAS sample exceeding the threshold of 10,000, when significant GWAS results can be expected to emerge. Achieving the large samples that are needed in GWAS can be especially difficult for psychiatric diagnoses, which require intensive clinical 108

evaluations. Major depressive disorder, which with more than 75,000 cases is the largest GWAS sample in Table 5.2, illustrates one strategy for building a large sample (Hyde et al., 2016). This study used the 23andMe database; respondents were simply asked whether they had ever been diagnosed with depression. Although a self-reported diagnosis has obvious limitations, it does allow for a large sample, and the depression GWAS produced more significant SNP associations than all other psychiatric diagnoses other than schizophrenia. Depression also illustrates another strategy for building large GWAS samples, known as the proxy phenotype strategy. There is considerable evidence that the personality trait of neuroticism is highly genetically correlated with depression. Consequently, neuroticism, self-report measures of which are available in many samples, can serve as a proxy for depression. The 11 SNP associations with neuroticism reported in the GWAS of more than 170,000 respondents provide likely candidates for depression (Okbay et al., 2016). Although we are at the early stages of GWAS with mental health phenotypes, several general conclusions are warranted. The phenotypic effect of any single variant identified in GWAS is likely to be very small. At the start of the candidate gene era, psychiatric geneticists assumed moderate effect sizes for individual genetic variants, ORs of approximately 2.0 in case–control comparisons, and r2s of 1% to 2% for quantitative traits. It is now known that the effect associated with any single GWAS-identified variant is likely to be very small. The SNP with the lowest p value (3.5*10−31) in the most recent schizophrenia GWAS had a frequency of .864 in cases and .850 in controls, yielding an OR of 1.21 (Schizophrenia Working Group of the Psychiatric Genomics Consortium, 2014). In the GWAS of quantitative traits by Okbay et al. (2016), the largest individualvariant r2 was .011% for neuroticism, .003% for subjective well-being, and .002% for depression symptoms. One implication of the very small effect associated with any single variant in a GWAS is that there must be a large number, likely thousands, of variants influencing risk for any specific disease phenotype. Indeed, the aggregate effect of known GWAS variants accounts for a very small portion

Behavioral Genetic Insights on the Development of Psychopathology

Table 5.2 Genome-Wide Association Studies of Representative Mental Health Disorders of Quantitative Behavioral Phenotypes Phenotype

ns

Study

No. of

Proportion

Total SNP

independent

of variance

heritability

genome-wide accounted for

(SE )a

significant

by significant

SNPs

SNPs

108

.034

.19 (.007)

5

NR

.23 (.010)

17

NR

.21 (.021)

0 0

0 0

.17 (.025) .28 (.023)

0 3 11 2

0 .0003 .0025 .0006

.027 (.060) .040 (.002) .091 (.007) .047 (.004)

Copyright American Psychological Association. Not for further distribution.

Mental health diagnoses Schizophrenia Bipolar disorder Major depressive disorder Autism spectrum disorder Attention-deficit/hyperactivity disorder

Schizophrenia Working Group 32,405 cases, of the Psychiatric Genomics 113,075 controls Consortium (2014) Mühleisen et al. (2014) 9,747 cases, 14,278 controls Hyde et al. (2016) 75,607 cases, 231,747 controls Chaste et al. (2015) 2,576 families L. Yang et al. (2013) 1,040 cases, 963 controls Quantitative phenotypes

Extraversion Subjective well-being Neuroticism Depression symptoms

van den Berg et al. (2016) Okbay et al. (2016) Okbay et al. (2016) Okbay et al. (2016)

63,030 298,420 170,911 180,866

Note. NR = not reported; SE = standard error; SNP = single nucleotide polymorphism. aTotal SNP heritability reported in the Genome-wide association studies for quantitative phenotypes and in Lee et al. (2013) for mental health diagnoses.

of heritable variation. Taking schizophrenia as an example, the 108 SNP variants identified by GWASs account for 3.4% of schizophrenia liability variance; biometric estimates of the heritability of schizophrenia liability are on the order of 60% to 80%. The difference between the biometric estimates of heritability from twin studies and the cumulative effect of SNPs identified in GWASs is known as the missing heritability problem.

Missing Heritability Despite massive sample sizes, the variants identified in GWASs account for only a small portion of the heritable variation; most of the heritability is “missing” (Manolio et al., 2009). Several factors have been posited as contributing to missing heritability. First, it may be that twin studies have systematically overestimated heritability (Zuk,

Hechter, Sunyaev, & Lander, 2012). Although this possibility cannot be ruled out, missing heritability characterizes virtually all phenotypes that have been investigated with GWASs. Consequently, for this to be a major contributor to missing heritability would require there to be a general bias in twin studies that leads to overestimated heritability with behavioral and nonbehavioral phenotypes. A second possibility is that the GWAS samples are not large enough to detect all relevant SNP variants. The increase in the number of detected SNP associations with increasing sample size in GWASs of schizophrenia suggests that additional variants would be identified with larger samples. There is a statistical procedure that can estimate the total variance that could be accounted for by all genotyped SNPs without specifying which of these SNPs are associated with the phenotype (J. A. Yang, Lee, 109

Copyright American Psychological Association. Not for further distribution.

McGue, Saunders, and Gottesman

Goddard, & Visscher, 2011). This heritability estimate, which is often called the SNP heritability, is reported in the final column of Table 5.2. The SNP heritabilities for the mental health diagnoses are all moderate in magnitude, suggesting that larger GWAS samples should identify additional SNP variants. Interestingly, the SNP heritabilities for the quantitative traits are very small, suggesting that GWAS of these phenotypes may produce limited results even with very large samples. A third possible source of missing heritability is nonadditivity. Statistical analysis in GWASs is based on an additive model of variant effects. Each genetic variant is represented by an additive count of a single allele, so that nonadditive within-locus (i.e., dominance) effects are not included, and are analyzed separately from the effects of other variants, so that synergies among loci (i.e., epistasis) are also not modeled. Although failure to consider nonadditive models may contribute to missing heritability, it is not likely to have a large effect given the limited evidence for nonadditive genetic effects from other sources (Hill et al., 2008). Finally, and perhaps most significant, GWAS only investigates common SNPs, a subset of the genetic differences that exist in the population. For example, both the 5-HTTLPR variant, which is an insertion–deletion, and the DAT1 variant, which is a VNTR, which have been the target of considerable candidate gene research, are not captured by GWAS genotyping platforms. Copy number variants (CNVs) are also not captured but are known to contribute to psychopathology risk. CNVs are regions of the genome ranging from kilobases to several megabases of DNA that are either duplicated or deleted (Kirov, 2015). Although CNVs can be inherited, most are de novo (i.e., new) mutations that occurred during the process of gametogenesis and so are associated with sporadic instances of disease. CNVs are rare, with population frequencies much less than one per thousand, but they can potentially have a large phenotypic effect because of the large number of bases, often spanning multiple genes, that are either deleted or duplicated. Williams syndrome, for example, is a unique behavioral disorder characterized by intellectual disability, especially in the visuospatial domain, and an overly friendly 110

personality (Martens, Wilson, & Reutens, 2008). The syndrome, which is almost always sporadic, affects about one in every 7,500 births and is due to a deletion of approximately 1.5 million DNA bases on chromosome 7q. Some CNVs increase risk for a specific form of psychopathology. For example, deletion of approximately three megabases of DNA on chromosome 22q (variously known as velocardiofacial syndrome, DiGeorge syndrome, or 22q11.2 deletion syndrome) is associated with a 20- to 30-fold increase in schizophrenia risk. Alternatively, many CNVs convey risk for multiple neuropsychiatric disorders. For example, deletion of approximately 600 kilobases on chromosome 16p11.2 increases risk for autism, intellectual disability, and epilepsy; duplication of the same region is associated with increased risk for schizophrenia, autism, and intellectual disability (Coe, Girirajan, & Eichler, 2012). The region on 7q that when deleted leads to Williams syndrome appears to result in increased risk of schizophrenia when duplicated (Kirov, 2015). Although CNVs can have a large effect on psychopathology risk, because they are rare they account for only a small portion of missing heritability. It is estimated, for example, that from 5% to 7% of individuals with autism spectrum disorder (ASD; Geschwind & State, 2015) and 2% to 3% of individuals with schizophrenia carry a CNV associated with increased psychopathology risk. Findings with CNVs raise the general issue of the contribution of rare variants to psychopathology risk. Recall that GWAS is designed to detect the effect of common variants (i.e., those with a frequency of 1% or greater) under the CDCV model. An alternative model is the common disease–rare variant, or CDRV, model (Pritchard & Cox, 2002). Under the CDRV model, inherited disease is the consequence of many different rare variants, each of which can have a large effect on phenotypic risk. Breast cancer provides a useful illustration of the CDRV model (McClellan & King, 2010). Mutations in any one of 13 different genes are associated with an inherited form of breast cancer. Each of these mutations is rare but associated with a substantial increase in breast cancer risk. A woman who develops an inherited form of breast cancer typically carries a mutation in only one of these genes.

Copyright American Psychological Association. Not for further distribution.

Behavioral Genetic Insights on the Development of Psychopathology

Rare variant associations can be difficult to establish, often requiring very large samples to provide adequate sensitivity and DNA sequencing in order to identify novel variants that have not been previously catalogued. Nonetheless, there is support for the contribution of rare variants to psychopathology risk, especially with ASD and schizophrenia. Indirect support for a role of rare variants comes from studies on paternal age effects. Risk for ASD and schizophrenia increases with paternal age independent of any association with maternal age (McGrath et al., 2014). Paternal age effects are observed with many rare genetic diseases (e.g., progeria, hemophilia) and are thought to be a consequence of de novo mutations transmitted through sperm (i.e., de novo mutations in the sequence of DNA usually arise during cell division and new sperm are continuously being produced through meiosis, whereas a woman is born with all her eggs). On average, people inherit approximately 50 to 60 de novo mutations, most of which come through the father’s sperm. The rate of de novo mutation increases by approximately two per year of father’s age (Goldmann et al., 2016). Thus, a 45-year-old father would on average transmit about 40 more mutations than a 25-year-old father. Nonetheless, although rare de novo mutations likely contribute to the paternal age effect observed with ASD and schizophrenia, they are unlikely to fully account for that effect; other factors must be at play (Gratten et al., 2016). The study by Purcell et al. (2014) illustrates the challenges associated with obtaining evidence of the contribution of specific rare variant effects. The study included approximately 2,500 individuals with schizophrenia and an equal number of controls, and it involved the sequencing of the coding regions of 2,546 genes selected as candidates on the basis of GWAS and CNV findings. Individuals with schizophrenia were found to carry a heavier overall burden of rare mutations (frequency