Early Clinical Intervention and Prevention in Schizophrenia PDF
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EARLy CLINICAL INTERVENTION AND PREVENTIONI N SCHIZOPHRENIA EARLy CLINICAL INTERVENTION AND PREVENTION IN SCHIZOPHRENIA Edited by WILLIAM S. STONE, phD HarvardI nstituteo fP sychiatric Epidemiologya nd Genetics, and HarvardM edical School Departmento fP sychiatry at MassachusettsM ental Health Center, Boston, A1A V. STEPHEN FARAONE, phD HarvardI nstituteo fP sychiatric Epidemiologya nd Genetics, and HarvardM edical School Departmento fP sychiatry at Massachusetts General Hospital, Boston, A1A MING T. TSUANG, MO, phD, OSc HarvardI nstituteo fP sychiatric Epidemiologya nd Genetics, HarvardM edical School Departmentso fP sychiatry at MassachusettsM ental Health Center and Massachusetts General Hospital, and Departmento fE pidemiology, Harvard School ofP ublic Health, Boston, A1A ~ HUMANA PRESS ~ TOTOWA, NEW JERSEY © 2004 HumanaP ress Inc. 999 Riverview Drive, Suite 208 Softcover reprinto f the hardcover1 s t edition 2004 Totowa, New Jersey 07512 humanapress.com For additionalc opies, pricing for bulk purchases, andlor informationa bout other Humanat itles, contact Humanaa t the above addresso r at any of the following numbers:T el: 973-256-1699; Fax: 973-256-8341; E-mail: [email protected];websiteathumanapress.com All rights reserved. No parto f this book may be reproduced,s tored in a retrievals ystem, or transmittedi n any form or by any means, electronic, mechanical, photocopying, microfilming, recording, or otherwise without written permissionf rom the Publisher. 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For those organizationst hat have been granteda photocopy Iicense from the CCC, a separate system of paymenth as been arrangeda ndi s acceptablet o the HumanaP ress. The fee code for userso ftheT ransactional ReportingS ervice is 1-58829-001-8/04 $25.00. Libraryo f Congress Cataloging-in-PublicationD ata Early clinical interventiona nd preventioni n schizophrenia/ edited by William S. Stone, Stephen V. Faraone,M ing T. Tsuang. p. ;cm. Includes index. ISBN 978-1-4684-9833-2 ISBN 978-1-59259-729-1 (eBook) DOI 10.1007/978-1-59259-729-1 Additional material to this book can be downloaded from http://extras.springer.com 1. Schizophrenia--Prevention.2.S chizophrenia--Etiology.3 . Schizophrenia--Riskf actors. [DNLM: 1. Schizophrenia--genetics.2. Schizophrenia--prevention& control. WM 203 EI25 2004] I. Stone, William S., PhD. 11. Faraone,S tephen V. III. Tsuang, Ming T., 1931- RC514.E24 2004 616.89'8205--dc21 2003014324 PREFACE The primaryg oals of schizophreniar esearcha ret o understandt he causes of the disordera ndt o attenuatei ts symptoms.A dvancesi n diagnosis andt reatmenth ave produceds ignificantp rogresst owardt hese aims, but there are still many hurdles to clearb efore the biological, genetic, and environmentale tiologies of the illness are understoodf ully. Similarly,m uchw orki s neededt o alleviate the residuala nd positive symptomsa ssociatedw ith schizophrenia.O ne importantc onsequenceo f our progress to date combines our understandingo f the etiology of the disorder with ouru nderstandingo f treatmento ptions. Therei s a clearc onsensust hatb etter outcomes are associated with earlieri nitiationo f treatment. In fact, if a list of "holyg rails"c ould be identifiedi n schizophreniar esearch,n one would rankh ighert hant he developmento f strategiesa imed at preventingt he onset of the disorder.P reventioni tself, however, is a multidimensionalc oncept, and our currentd istancef rom the grail dependso n which dimensioni s the focus of attention. Althoughp rimaryp reventionr emainsf urthero ff on the horizon, early intervention for psychosis andt he developmento f psychosis (i.e., the prodrome)a re active areas of investigation.O ne of the most significanti mpedimentst o bothe arlyi ntervention and preventionr esearchi s thatw e do not yet know what the liability to schizophre- nia looks like. We do not know who will develop the disordera nd who will not. As a result, we do not know who should receive treatmentb efore theirc linical symp- toms become overt. This becomes more evident as the distance from psychosis increases. Prodromals ymptoms,w hich are a targeto f many currentm odels of early intervention,a re often nonspecific for schizophrenia.P roblems that may precede prodromals ymptoms, such as negative symptoms, are even less clearly points on a trajectoryt o psychosis, as aret he absenceo f clinical symptomso ro thera bnormali- ties (e.g., neuropsychological,p sychophysiological,o r neurobiologicald eficits) in individuals with one or more risk factors for schizophrenici llness, such as those with a family history of the disorder,p regnancy,o r obstetricc omplications. Fortunately,t he situation is improving. High-risk longitudinal studies and family studies now identify a range of likely clinical, biological, cognitive, and social problems in relatives of patients with schizophreniat hat may represent liability/vulnerabilityf actors. A recent reformulationo f Paul Meehl's concept of schizotaxia supportst he view that one or more liability syndromesm ight be identifieda nd validated.T herei s also growing attentiont o the naturea nd delin- eation of the prodrome.B ecause interesti n the preventiono f schizophreniai s high, and characterizationo f liability syndromesh as the potentialt o move pre- v vi Preface vention researchf orward, the time seems right for a volume on prevention in schizophrenia. Early Clinical Interventiona nd Prevention of Schizophrenia focuses on the status of preventionr esearchw ithin the broaderc ontext of our currentk nowledge of the causes and early treatmentso f schizophrenia,w ith the goal of determining how early we can intervene in schizophrenic illness. To accomplisht his aim, we invited experts working in the field to contributec hap- ters in the frameworko f four majors ections. We also emphasizedo ur reformu- lation of schizotaxiat o substantiatet he notion thatt he liability to schizophrenia often manifests itself with meaningful clinical, neuropsychological,s ocial, and neurobiologicalc oncomitants. The first section reviews the origins of schizophrenia.I n ordert o develop rational interventions,i t is crucialt o understandw hatc auses the illness and how it develops. Thus, this section focuses on the genetic (Steve Faraone and colleagues), early environmenta(l SarnoffM ednicka ndc olleagues), andn eurodevelopmenta(lS tefano Marencoa nd Daniel Weinberger)d eterminantso f schizophrenia. With this frameworki n mind, the second section characterizesc urrentv iews of the vulnerabilityt o schizophrenia.I n particular,i t explores the natureo f the liability from several dimensions, including the prodrome( Jaak Rakfeldt and Thomas McGlashan)a nd our proposedp re-prodromasl yndromeo f schizotaxia (Steve Faraonea nd colleagues). More specific manifestationso f schizotaxia- used here in a generic sense to describe the liability to schizophrenia-include cognitive deficits in high-riskp opulations( Allan Mirsky and Connie Duncan) and in adult, nonpsychotic, biological relatives of patients with schizophrenia (William Kremen and AnneH off), socioemotional deficits (Elaine Walkera nd Karen Hochman), neuroanatomicala bnormalities (Larry Seidman and col- leagues), and neurophysiological deficits (Marina Myles-Worsley). Finally, Robin Murraya nd colleagues review several of the dimensions consideredi n previous chapterst o determinew hethers chizophreniai s actually predictable. The most importantv alue of characterizingt he liability to develop schizo- phreniai nvolves, arguably,t he identificationo f treatment/interventionta rgets. In this light, the thirds ection addressesi ssues of early interventiona nd preven- tion more directly. Following a discussion of conceptual and methodological considerationsn ecessary for the design and implementationo f preventionp ro- tocols (HendricksB rowna nd Steve Faraone),t he focus turnst o protocolsf or the treatmento f schizotaxia (Ming Tsuang and colleagues), prodromals ymptoms (BarbaraC ornblatta nd colleagues), and issues related to genetic counseling (Debby Tsuang and colleagues). Finally, the last section looks ahead to the nearf utureo f preventionr esearch from two vantage points. One involves representativen eurochemicala reas that are relevantf or schizotaxiar esearch,b ut are in need of additionali nvestigation Preface Vll (William Stone and colleagues), and the othere xplores the prospectso f molecu- lar biology for advancing the goals of preventiona nd early intervention( Will Carpentera nd James Koenig). Early Clinical Interventiona nd Prevention of Schizophrenia explores the multidimensionaln atureo fthe liability to schizophrenia,o ften in the absence of psychosis or even a schizophrenia-relatedc linical diagnosis. Although prodro- mal or psychotic symptomsa re alreadyt argetso f active investigations,i t is clear thatp re-prodromailn terventionb asedo n clinical symptomso r cognitive deficits remainsp remature.Y et, as many of the authorsi n this volume demonstrate,t he field is at the point of mapping strategies and validating interventiont argets. Together with currente fforts to attenuatep rodromala nd incipient psychotic symptoms, these developments bring us closer to the thresholdo f prevention studies. It is hoped thatt he multidimensionala nd interdisciplinary descriptioonf these efforts will benefit everyone interestedi n the preventiono f schizophrenia, and moreb roadly,a nyone interestedi n the preventiono f majorm entald isorders. William S. Stone, PhD Stephen V. Faraone, PhD Ming T. Tsuang, MD, PhD, DSc CONTENTS Preface ............................................................................................................... v Contributors.. .................................................................................................... xi Value-Addede BooklPDA ............................................................................. xiv PART I. THE ETIOLOGYA ND GENETICS OF SCHIZOPHRENIA 1 The Genetic Basis of Schizophrenia. .................................................. 3 Stephen V. Faraone, Stephen J. Glatt, and Levi Taylor 2 Early EnvironmentalD eterminantso f Schizophrenia.. .................... 23 Jason Schiffman,J ohn Carter, Ricardo A. Mach6n, and SarnoffM ednick 3 ObstetricR isk Factorsf or Schizophreniaa nd Their Relationshipt o Genetic Predisposition:F ollowing Ariadne's Double-StrandedT hread Through Early Development ............ 43 Stefano Marenco and Daniel R. Weinberger PART II. THE VULNERABILITYT O SCHIZOPHRENIA 4 The Natureo f the Prodromei n Schizophrenia. ................................ 75 Jaak Rakfeldta nd Thomas H. McGlashan 5 The Nature of Schizotaxia ................................................................ 93 Stephen V. Faraone, Ming T. Tsuang, and Sarah I. Tarbox 6 A NeuropsychologicalP erspectiveo n Vulnerability to Schizophrenia:L essons From High-RiskS tudies. ............... 115 Allan F. Mirskya nd Connie C. Duncan 7 NeurocognitiveD eficits in the Biological Relatives of IndividualsW ith Schizophrenia. .......................................... 133 William S. Kremena nd AnneL . Hoff 8 The Nature and Origin of Socioemotional Deficits in Schizophrenia. ...................................................................... 159 Elaine Walkera nd Karen M. Hochman 9 NeuroimagingS tudies of Nonpsychotic First-DegreeR elatives of People With Schizophrenia:T owarda Neurobiology of Vulnerabilityt o Schizophrenia. ............................................ 179 LarryJ . Seidman, Heidi E. Wencel, Colm McDonald, Robin M. Murray, and Ming T. Tsuang ix x Contents 10 NeurophysiologicalE ndophenotypesi n Early Detection of Schizophrenia. ...................................................................... 211 Marina Myles-Worsley 11 Is the Development of SchizophreniaP redictable?. ..................... 225 Paola Dazzan, Eugenia Kravariti, Paul Fearon, and Robin M. Murray PART III. EARLY INTERVENTIONA ND PREVENTION OF SCHIZOPHRENIA 12 Preventiono f Schizophreniaa nd Psychotic Behavior: Definitions and Methodological Issues .................................... 255 C. HendricksB rown and Stephen V. Faraone 13 The Treatmento f Schizotaxia. ....................................................... 285 Ming T. Tsuang, Sarah I. Tarbox, Levi Taylor, and William S. Stone 14 Treatmento f the SchizophreniaP rodrome. ................................... 303 Barbara Cornblatt, Todd Lencz, ChristopherS mith, and AndreaA uther 15 The Role of Genetic Counseling. ................................................... 325 Debby W. Tsuang, Stephen V. Faraone, and Ming T. Tsuang PART IV. CHALLENGES FOR THE NEAR FUTURE 16 The Biology of Schizotaxia ........................................................... 339 William S. Stone, Stephen J. Glatt, and Stephen V. Faraone 17 MolecularM edicine and the Prospects for Prevention and Early Interventioni n Schizophrenia. ................................. 355 William T. Carpenter, Jr. and James I. Koenig Index .............................................................................................................. 367 CONTRIBUTORS ANDREA AUTHER, PhD • Departmento fP sychiatryR esearch, The Zucker Hillside Hospital of the North Shore-LongI sland Jewish Health System, Glen Oaks, NY C. HENDRICKS BROWN, phD • Departmento fE pidemiologya nd Biostatistics, College ofP ublic Health, University ofS outh Florida, Tampa, FL and Departmentso fB iostatistics and Mental Hygiene, The Johns Hopkins BloombergS chool ofP ublic Health, Baltimore, MD WILLIAM T. CARPENTER, JR., MD • Departmento f Psychiatry, University ofM arylandS chool ofM edicine and MarylandP sychiatric Research Center, Baltimore, MD JOHN CARTER, MA • Social Science Research Institute, University ofS outhernC alifornia, Los Angeles, CA BARBARA CORNBLATT, phD • Departmento fP sychiatryR esearch, The Zucker Hillside Hospital oft he North Shore-LongI sland Jewish Health System, Glen Oaks, NY PAOLA DAZZAN, MD, MSc, MRCPsych • Division ofP sychological Medicine, Instituteo fP sychiatry, London, United Kingdom CONNIE C. DUNCAN, phD • Clinical Psychophysiologya nd Pharmacology Laboratory,D epartmento f Psychiatry, UniformedS ervices University of the Health Sciences and Section on Clinical and Experimental Neuropsychology, National Instituteo fM ental Health, Bethesda, MD STEPHEN V. FARAONE, phD· HarvardI nstituteo fP sychiatric Epidemiology and Genetics, and HarvardM edical School Departmento f Psychiatry at MassachusettsG eneral Hospital, Boston, MA PAUL FEARON, MB, MSc, MRCPI, MRCPsych· Division ofP sychological Medicine, Instituteo f Psychiatrya nd Guy's, King's and St. Thomas's School ofM edicine, London, United Kingdom STEPHEN J. GLATT, phD· Departmento f Psychiatry, HarvardM edical School, Departmento f Psychiatrya t MassachusettsM ental Health Center; HarvardI nstituteo fP sychiatric Epidemiologya nd Genetics, Boston, MA KAREN M. HOCHMAN, MD • Departmento f Psychiatrya nd Behavioral Science, Emory University School ofM edicine, Atlanta, GA ANNE L. HOFF, phD • Departmento fP sychiatrya nd Behavioral Sciences, University of California, Davis School ofM edicine, Sacramentoa nd Napa State Hospital, Napa, CA xi Xli Contributors JAMES I. KOENIG, phD • Departmento f Psychiatry, University ofM aryland School ofM edicine and MarylandP sychiatric Research Center, Baltimore, MD EUGENIA KRAVARITI, MA, MSc, phD • Division of Psychological Medicine, Insti- tute of Psychiatry, London, United Kingdom WILLIAM S. KREMEN, phD • Departmento f Psychiatry and Behavioral Sciences, University of California, Davis School ofM edicine, Sacramento and Napa State Hospital, Napa, CA TODD LENCZ, PhD • Departmento f PsychiatryR esearch, The Zucker Hillside Hospital of the North Shore-LongI sland Jewish Health System, Glen Oaks, NY RICARDO A. MACHON, PhD • Departmento f Psychology, Loyola Marymount University, Los Angeles, CA STEFANO MARENCO, MD • Clinical Brain Disorders Branch, National Institute ofM ental Health, Bethesda, MD COLM McDoNALD, MB, MRCPsych • Division ofP sychological Medicine, Instituteo f Psychiatry, London, United Kingdom THOMAS H. MCGLASHAN, MD • Departmento f Psychiatry, Yale Psychiatric Research Center, Yale University, New Haven, CT SARNOFF MEDNICK, phD, MD • Social Science Research Institute, University ofS outh California, Los Angeles, CA ALLAN F. MIRSKY, PhD· Section on Clinical and ExperimentalN europsychology, National Instituteo fM ental Health, Bethesda, MD ROBIN M. MURRAY, MD, FRCPsych, DSc· Division of Psychological Medicine, Instituteo f Psychiatry, London, United Kingdom MARINA MYLES-WORSLEY,p hD • Departmento f Psychiatry, University of Utah School ofM edicine, Salt Lake City, UT JAAK RAKFELDT, phD· Social WorkD epartment,S outhernC onnecticutS tate University and Departmento fP sychiatry, Yale University, New Haven, CT JASON SCHIFFMAN, phD • Departmento f Psychiatry, University of Hawaii at Manoa, Honolulu, HI LARRY J. SEIDMAN, phD • Departmento fP sychiatry, HarvardM edical School; Departmento f Psychiatrya t MassachusettsM ental Health Center, BrocktonlWestR oxburyV A Medical Center and MassachusettsG eneral Hospital, HarvardI nstituteo f Psychiatric Epidemiologya nd Genetics, Boston, MA CHRISTOPHERS MITH, MA • Departmento f PsychiatryR esearch, The Zucker Hillside Hospital of the North Shore-LongI sland Jewish Health System, Glen Oaks, NY
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