Early Clinical Intervention and Prevention in Schizophrenia

373 Pages·2004·7.259 MB·English

by  Stephen V. Faraone PhD, Stephen J. Glatt PhD, Levi Taylor PhD (auth.), William S. Stone PhD, Stephen V. Faraone PhD, Ming T. Tsuang MD, PhD, DSc (eds.)

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
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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