Neurobiology of Psychiatric Disorders PDF
Preview Neurobiology of Psychiatric Disorders
HANDBOOK OF CLINICAL NEUROLOGY Series Editors MICHAEL J. AMINOFF, FRANC¸OIS BOLLER, AND DICK F. SWAAB VOLUME 106 EDINBURGH LONDON NEW YORK OXFORD PHILADELPHIA ST LOUIS SYDNEY TORONTO 2012 ELSEVIERB.V Radarweg29,1043NX,Amsterdam,TheNetherlands #2012ElsevierB.V.Allrightsreserved. Nopartofthispublicationmaybereproducedortransmittedinanyformorbyanymeans,electronicor mechanical,includingphotocopying,recording,oranyinformationstorageandretrievalsystem,without permissioninwritingfromthepublisher.PermissionsmaybesoughtdirectlyfromElsevier’sRightsDepartment: phone:(þ1)2152393804(US)or(þ44)1865843830(UK);fax:(þ44)1865853333;e-mail: healthpermissions@elsevier.com.Youmayalsocompleteyourrequeston-lineviatheElsevierwebsiteat http://www.elsevier.com/permissions. ThisbookandtheindividualcontributionscontainedinitareprotectedundercopyrightbythePublisher(otherthan asmaybenotedherein). 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ThePublisher PrintedinChina The Publisher's CommissioningEditor:MichaelHouston policy is to use DevelopmentEditor:MichaelParkinson paper manufactured from sustainable forests ProjectManager:AnnieVictor Designer:KirsteenWright Handbook of Clinical Neurology 3rd Series Availabletitles Vol.79, The humanhypothalamus: basic and clinicalaspects, Part I, D.F. Swaab ISBN 9780444513571 Vol.80, The human hypothalamus: basic and clinical aspects,Part II, D.F. Swaab ISBN 9780444514905 Vol.81, Pain, F.Cerveroand T.S. Jensen, eds. ISBN 9780444519016 Vol.82,Motor neurone disorders and relateddiseases, A.A. Eisenand P.J.Shaw, eds.ISBN9780444518941 Vol.83, Parkinson’s diseaseand relateddisorders, Part I, W.C.Koller and E. Melamed,eds. ISBN 9780444519009 Vol.84,Parkinson’sdiseaseandrelateddisorders,PartII,W.C.KollerandE.Melamed,eds.ISBN9780444528933 Vol.85, HIV/AIDS and thenervoussystem, P. Portegiesand J. Berger, eds. ISBN 9780444520104 Vol.86, Myopathies, F.L. Mastaglia and D. Hilton Jones, eds.ISBN9780444518996 Vol.87, Malformations ofthe nervous system, H.B. Sarnat and P. Curatolo, eds.ISBN 9780444518965 Vol.88, Neuropsychology and behaviouralneurology,G.Goldenberg and B.C.Miller, eds. ISBN 9780444518972 Vol.89, Dementias, C.Duyckaerts and I.Litvan, eds. ISBN 9780444518989 Vol.90, Disorders ofconsciousness, G.B. Young and E.F.M. Wijdicks, eds. ISBN 9780444518958 Vol.91, Neuromuscular junction disorders, A.G. Engel, ed. ISBN 9780444520081 Vol.92, Stroke – Part I:Basicand epidemiologicalaspects, M.Fisher, ed.ISBN9780444520036 Vol.93, Stroke– Part II: Clinical manifestations and pathogenesis,M. Fisher, ed. ISBN 9780444520043 Vol.94,Stroke– Part III:Investigationsand management, M.Fisher, ed. ISBN 9780444520050 Vol.95, Historyofneurology, S.Finger, F.Boller and K.L. Tyler, eds. ISBN 9780444520081 Vol.96, Bacterialinfectionsofthecentralnervoussystem,K.L. RoosandA.R. Tunkel, eds.ISBN9780444520159 Vol.97, Headache, G. Nappi and M.A. Moskowitz, eds.ISBN9780444521392 Vol.98, Sleep disorders, Part I, P.Montagna and S.Chokroverty,eds. ISBN 9780444520067 Vol.99, Sleep disorders,Part II, P. Montagna and S. Chokroverty,eds.ISBN 9780444520074 Vol.100,Hyperkineticmovement disorders,W.J. Weiner and E. Tolosa, eds.ISBN 9780444520142 Vol.101,Muscular dystrophies,A.Amato and R.C.Griggs, eds.ISBN 978 0 080450315 Vol.102, Neuro-ophthalmology, C. Kennard and R.J. Leigh, eds.ISBN9780444529039 Vol.103,Ataxicdisorders, S.H. Subramony and A.Durr,eds.ISBN 9780444518927 Vol.104,Neuro-oncology,Part I, W. Grisoldand R. Sofietti, eds. ISBN 9780444521385 Vol.105,Neuro-oncology,Part II, W. Grisold and R. Sofietti,eds. ISBN 9780444535023 Foreword Wearepleasedtopresent,forthefirsttime,avolumeintheHandbookofClinicalNeurologyseriesdevotedexclu- sivelytopsychiatricdisorders.ItistruethatVolumes45and46ofthesecondseries–onClinicalNeuropsychology andNeurobehavioralDisorders–hadafewchaptersthatdealtwithaspectsofthemajorpsychiatricdisorders,but thesewerelimitedinscopeandnumber.Thevolumeswerepublishedin1985,whentherewasstillastrictseparation and even animosity between thefields ofneurology and psychiatry.GeorgeW. Bruyn,oneofthefoundersofthe HCN series, however, was not convinced of any fundamental difference between these two disciplines and stated boldly that, “psychiatry is nothing but unexplained neurology.” Many neurologists of the late nineteenth and early twentieth century felt quite at home with psychiatry, which was then considered to be a special branch of neurology, a point of view shared by such luminaries as Charcot, Meynert,Von Monakow, Edinger,Wernicke,Spielmeyer,Pick,and Von Gudden.Inthosedays, mostmentalhos- pitals had a laboratory for anatomy and pathology. Many of the famous university professors held chairs in both neurology and psychiatry, as they were interested in both the clinical and the fundamental aspects of the central nervoussystem.Foralongtimeformalizedresidencytrainingincludedbothpsychiatryandneurology,andtheterm “neuropsychiatry” was coined, to illustrate theintegration ofthetwo fields. Psychotherapy,developedbySigmundFreudintheearly1900s,wastheprincipalmethodoftreatmentformental disordersthroughoutthe1950s.Theemergenceofanalyticalpsychiatrygraduallyledtoaschismbetweenneurology andpsychiatry.Forinstance,intheNetherlandsthisresultedinacompleteseparationbetweenthetwowhen,in1974, theDutchSociety forNeurology and Psychiatry was split into two separatesocieties. Inthemeantime,inthelate1950s,thefirstantipsychoticandantidepressantdrugscameintowidespreaduseand theirclinicaleffectsresultedin“chemicalimbalance”hypotheses ofmentaldisorders.Thisformedtheconceptual basisforthedevelopmentof“biologicalpsychiatry”:researchnowfocusedonthebrainitselfandontheneurobio- logicalmechanismsthatcauseddisorderssuchasdepressionandschizophrenia.Wehavethus,inasense,comefull circle to a situation where the differences and borders between psychiatry and neurology are once again blurred. Mentalillnessesarenowconsideredtobegeneticallyandenvironmentallyinfluenceddisordersofbrainchemistry. Theemergenceanddevelopmentofimagingtechniqueshavecontributedtremendouslytotheshiftofattentionto the neurosciences in psychiatry. The structural and molecular basis of neuropsychiatric disorders is becoming clearer,makingthe present volume anextremely timely one. We congratulate the two volume editors, Thomas Schlaepfer and Charles Nemeroff, for putting together this outstandingvolume,whichwillappealtopsychiatrists,neurologistsandneuroscientistsalike.Clinical,genetic,molec- ular, imaging,neuropathological, immunological,epidemiological,metabolic, therapeutic and historicalaspects of the major psychiatric disorders are reviewed in a thoughtful and scholarly manner. In addition, the potential and limitationsofanimalexperimentalmodelsforthesedisordersareextensivelydiscussed. AsalwaysweareverygratefultotheteamatElsevier,andespeciallytoMr.MichaelParkinson,forexpertassis- tance in thedevelopment and production ofthis volume. MichaelJ. Aminoff Franc¸oisBoller Dick F.Swaab Preface (cid:1)Idon’tconsiderthismyscience.Thisismyavocation.Butthatavocationhasbeencompletelyinfluencedby my science.(cid:3) EricKandelina1996lecturecommemoratingthe100thanniversaryoftheNewYorkStatePsychiatricInstitute, ColumbiaUniversityCollegeofPhysiciansandSurgeons. ThisvolumeonpsychiatricdisordersappearsforthefirsttimeintheprestigiousHandbookofClinicalNeurology series;aneventthataffirmsourbeliefofafundamentalconceptualshiftintheconceptualizationofmentaldisor- ders.Psychiatryisthemedicaldisciplinediagnosticallyassessingandtreatingpatientswithmultifacetedandcomplex brain disorders that represent the leading causes of disability worldwide. These disorders are highly prevalent; each year over 25% of adult Americans carry the diagnosis of at least one mental disorder and similar data has been reported for Europe. The public health impact of depression is in part due to the fact that available treatments are suboptimal; in the case of major depression, up to 40% of patients responding to antidepressant therapy suffer from clinically relevant residual symptoms despite optimized treatment and a large sequenced treatment (STAR*D) study, which analyzed outcome following several standardized treatment steps, reported that 33% of patients did not respond despite four evidence-based treatment steps. Historically, brain disorders of unknown etiology fell in the domain of psychiatry and those with known etiology in the domain of neurology. The quotation above by Eric Kandel was published in 1998. This paper and several others by him and others that predate it had a significant influence on the science of psychiatry, by addressing the conceptual shift from a purely psychoanalytic framework, often conceptualized as the antithesis of biological psychiatry, to the synthesis of psychiatry as a truly comprehensive, behavioral neuroscience. By studying the sea slug Aplysia and the fruit fly Drosophila, Kandel and his colleagues demonstrated that memory storage depends on the coordinated expres- sionofspecificgenes that codeforproteinsthatalter structural elementsofthebrain.Thisisparticularlynotable because Kandel, born in Vienna, connected after his immigration to the USA to that city’s psychiatric history by training as a psychoanalyst, a profession at that time far removed from the biological sciences. When Sigmund Freud – the founder of psychoanalysis – explored implications of unconscious mental processes for behavior, he tried to adopt a neuroscientific model of behavior in an attempt to develop a scientific psychology. He proposed that the cognitive mechanisms of normal and abnormal mental phenomena could be explained through orderly and rigorous study of brain systems. Given the state of scientific methodology in psychiatry at the time – mainly restricted to histopathology and assessing brain states by verbal reports of patient’s subjective experiences – this was a somewhatfutile attempt. Duringthe20thcentury,aseriesofrapidlychangingemphaseshavebeenprominentwithinpsychiatry,eachone dominating a period spanning two or more decades. These developments have contributed to both diffusion and confusionabout whatpsychiatry really isand what it stands for,ultimately affecting thecredibility oftheprofes- sion. The long-standing tradition of moving disorders from the domain of psychiatry to neurology once thepathophysiologywaselucidated,asoccurredwithpellagraandneurosyphilis,hasnowfinallyendedwithunder- standingthatthemajorpsychiatricdisordersareinfactbraindiseases.Researchonbraindisordershasledtonovel insights into etiology and pathogenesis using brain imaging techniques and molecular methods. Thus a number of genetic risk factors for psychiatric and neurological disorders have been identified and molecular pathological mechanisms are increasingly being scrutinized in appropriate experimental models. Molecular research has even leadtorecognitionofthebiologicalconsequencesandtransgenerationalimpactsofviolenceandabuse.Theappli- cation of the rapidly increasing knowledge base in molecular and cellular neurobiology into psychiatry presages a new understanding of psychiatric illness and its treatment, thereby overcoming the ideological struggles between x PREFACE biology and psychodynamics—a confrontation that often was detrimental to patient care. The application of evi- dence-based medicine to psychotherapeutic treatments has revealed the efficacy of cognitive behavior therapy (CBT),interpersonalpsychotherapy(IPT),dialecticalbehaviortherapy(DBT)andmostnotablyinsomerecentstud- ies,psychodynamicpsychotherapy.Molecularbiologicalresearchhasleadtonewhypothesesonbraindisorders;this researchwillundoubtedlyleadtoconceptuallynewtherapeuticstrategiesandtheunderstandingofthemechanisms ofactionofeffectivepsychopharmacologicalandpsychotherapeutictreatments.Inthefutureitwillbegermaneto strengthen translational research approaches, a process in which new basic research findings will be translated to clinical application – and from bench to bedside and back – clinical observations are fed back to basic research allowing thegenerationof newtestablehypotheses. In this volume we sought to provide a comprehensive and integrated view of psychiatric care and its current scientificfoundationsin45chapters.Togiveatrulyinternationaloverview–wellwithinthetraditionofSigmund FreudandEricKandel–weinvitedtwoauthorsforeachchapter,recognizedexpertsinthechapter’ssubjectarea, onefromtheUSAandonefromelsewhere.Inmostcasesthisambitiousgoalwasachieved,resultinginoutstanding reviewsofthetopicsreflectingtheinternationalstateofthescience.Eachchapterwasreviewedbytheeditorsand the series editors to assure completeness of coverage and quality. We truly believe that the burgeoning body of research on the pathogenesis and pathophysiology of psychiatric illness and the increasing number of treatments availabletopatientsreviewedinthisvolumeisatlastbeginningtoliftthestigmaofmentalillnessandofferinghope to thosewho sufferfrom it. Thomas E. Schlaepfer Charles B. Nemeroff Contributors J.L. Ayuso-Mateos R.M. Bonelli Psychiatry Department, Hospital Universitario dela DepartmentofNeuropsychiatry, Sigmund Freud Princesa, Universidad Auto´noma deMadrid, UniversityVienna, Vienna, Austria Madrid,Spain O.Boxer A.-M. Bao DepartmentofPsychiatry and Biobehavioral Sciences, Departmentof Neurobiology, Institute of David Geffen School ofMedicine atUCLA, and Neuroscience,ZhejiangUniversitySchoolofMedicine, DepartmentofPsychology,UCLACollegeofLetters& Hangzhou, China, and Netherlands Institutefor Science, and UCLA Semel Institute forNeuroscience Neuroscience,an institute oftheRoyalNetherlands and Human Behavior,Los Angeles,CA,USA Academy ofArtsand Sciences,Amsterdam,The Netherlands S. Brunnhuber DepartmentofPsychiatryandPsychotherapyII,SALK, M.F. Beal UniversityofSalzburg, Salzburg, Austria Departmentof Neurology and Neuroscience, Weill MedicalCollege ofCornellUniversity, New York, L.M.Cancela NY, USA DepartmentofPharmacology,University ofCordoba, Cordoba, Argentina M. Berger A.Ciaramella Departmentof Psychiatryand Psychotherapy, DepartmentofOncology, Azienda Ospedaliera UniversityMedicalCenterFreiburg,Freiburg,Germany UniversityofPisa, Pisa, Italy G.E. Berrios S. Claes Neuropsychiatry Service,University ofCambridge, DepartmentofPsychiatry, UniversityPsychiatric Cambridge,UK Center,CampusLeuven,UniversityofLeuven,Leuven, Belgium R.M.Bilder Departmentof Psychiatryand BiobehavioralSciences, L.Clark David Geffen School ofMedicineat UCLA,and DepartmentofExperimental Psychology, DepartmentofPsychology,UCLACollegeofLetters& MRC–Wellcome Trust Behavioural and Clinical Science, and UCLA Semel Institute for Neuroscience Neurosciences Institute,University ofCambridge, and Human Behavior, LosAngeles, CA, USA Cambridge, UK E.B.Binder M.Cristancho DepartmentofPsychiatryandBehavioralSciences and Clinical ResearchScholarsProgram,Departmentof Departmentof Genetics, Emory UniversityAtlanta, Psychiatry, Universityof Pennsylvania School of GA, USA,and Max Planck Instituteof Psychiatry, Medicine, Philadelphia, PA, USA Munich, Germany J.F.Cubells J. Blanch DepartmentofHumanGeneticsand Department of Psychiatry Department, Instituteof Neurosciences, Psychiatry and Behavioral Sciences,EmoryUniversity Hospital Clı´nic deBarcelona, Barcelona,Spain School ofMedicine,Atlanta,GA, USA xii CONTRIBUTORS K.V. Danilenko S. Gibiino Institute ofInternal Medicine, Siberian Branch ofthe Institute ofPsychiatry, Universityof Bologna, RussianAcademy of Medical Sciences,Novosibirsk, Bologna, Italy Russia C.F. Gillespie D.Denys Department ofPsychiatry and Behavioral Sciences, Department ofPsychiatry,Academic MedicalCentre, Emory University School ofMedicine, Atlanta, Amsterdam,The Netherlands GA, USA M. Deuschle J.M. Gorman CentralInstitute ofMental Health,Mannheim, Comprehensive Neuroscience Inc, WhitePlains, NY, Germany USA B.W. Dunlop L.Gray Moodand Anxiety Disorders Program,Emory ClinicalResearch Scholars Program,Department of University School ofMedicine,Atlanta,GA, USA Psychiatry,University ofPennsylvania School of Medicine, Philadelphia, PA, USA T.D. Ely Department ofPsychiatryand BehavioralSciences, B.Greenberg EmoryUniversitySchoolofMedicine,Atlanta,GA,USA Department ofPsychiatry and HumanBehavior, Brown University, Butler Hospital, Providence, E.J. Engstrom RI, USA Department ofHistory, HumboldtUniversity, Berlin, Germany C. Guilleminault Stanford UniversitySleep Disorders Program, C. Fassbender Stanford, CA, USA Department ofPsychiatryand BehavioralSciences, MIND Institute, University ofCalifornia Davis School P.D.Harvey ofMedicine, Sacramento, CA, USA Department ofPsychiatry and Behavioral Sciences, Emory University School ofMedicine, Atlanta, P. Fossati GA, USA Department ofPsychiatry,Salpeˆtrie`re Hospital, Paris, France U. Hegerl Department ofPsychiatry, Universityof Leipzig, G.Gabbard Leipzig, Germany Menninger Departmentof Psychiatryand Behavioral C.M.Heim Sciences,BaylorCollegeofMedicine,Houston,TX,USA Department ofPsychiatry and Behavioral Sciences, Emory University School ofMedicine, Atlanta, S.-F. Gao GA, USA Department ofNeurobiology, Instituteof Neuroscience,ZhejiangUniversitySchoolofMedicine, S.P. Henderson Powell Hangzhou, China Spring GroveHospital Center,Catonsville, MD, USA M. Gerardi Department ofPsychiatryand BehavioralSciences, B.Herpertz-Dahlmann EmoryUniversitySchoolofMedicine,Atlanta, Department ofChildand Adolescent Psychiatry, GA, USA RWTH Aachen University, Aachen, Germany M. Gerlach R.B. Hidalgo LaboratoryofClinicalNeurochemistry,Departmentof Department ofPsychiatry, Depressionand Anxiety Child and Adolescent Psychiatryand Psychotherapy, DisordersResearch Institute, UniversityofSouth University ofWu¨rzburg, Wu¨rzburg, Germany Florida College ofMedicine,Tampa,FL, USA S.N. Ghaemi K. Holtkamp Department ofPsychiatry,Tufts MedicalCenter, DRKClinic of Childand Adolescent Psychiatry, Boston, MA,USA Bad Neuenahr,Germany CONTRIBUTORS xiii P. Holtzheimer K.R.R. Krishnan Departmentof Psychiatryand Behavioral Sciences, DepartmentofPsychiatry and Behavioural Sciences, EmoryUniversity, Atlanta,GA, USA Duke UniversityMedicalCenter,Durham, NC, USA L.J. Hoppe R.A. Lanius ACSENTLaboratory, Department ofPsychology DepartmentofPsychiatry, UniversityofWestern and Department ofPsychiatry,University ofCape Ontario, London, Ontario,Canada Town, Medical Research CouncilofSouth Africa – Y.Lecrubier Anxiety and Stress DisordersUnit,Cape Town, French NationalInstitute ofHealth and Medical SouthAfrica Research (INSERM),Paris, France; now deceased N.S. Hudepohl R.D. Levitan Departmentof Psychiatry,University ofCincinnati DepartmentofPsychiatry, Centre forAddiction and College ofMedicine,Cincinnati, OH, USA MentalHealth,UniversityofToronto,Toronto,Canada J. Ipser A.R. Lingford-Hughes Departmentof Psychiatry,University ofCape Town, DepartmentofNeuropsychopharmacology, Imperial Groote Schuur Hospital, Cape Town, South Africa College, London, UK M.R.Irwin L.Lit CousinsCenter for Psychoneuroimmunology,Semel DepartmentofPsychiatry andBehavioralSciencesand Institute forNeuroscience, UniversityofCalifornia, DepartmentofNeurology, MIND Institute, University Los Angeles CA, USA ofCalifornia Davis Schoolof Medicine, Sacramento, CA, USA E.G. Iskander Mount Sinai Medical Center, New York, NY, USA D.Maust Clinical ResearchScholarsProgram,Departmentof S.H. Juul Psychiatry, Universityof Pennsylvania School of Departmentof Psychiatryand Behavioral Sciences, Medicine, Philadelphia, PA, USA EmoryUniversitySchoolof Medicine, Atlanta, GA, USA E.A. Mayer Center forNeurobiology ofStress, Divisionof P.W.Kalivas Digestive Diseases, David Geffen School ofMedicine Departmentof Neurosciences, MedicalUniversity of atUCLA,LosAngeles,CA,USA SouthCarolina,Charleston,SC, USA W. McDonald C. Kilts DepartmentofPsychiatry and BehavioralSciences, Brain ImagingResearch Center, PsychiatricResearch Emory University, Atlanta, GA, USA Institute,UniversityofArkansasforMedicalSciences, LittleRock,AR, USA J.McPartland DepartmentofPsychiatry, Yale ChildStudyCenter, K. Konrad New Haven, CT, USA NeuropsychologySection, DepartmentofChildand Adolescent Psychiatry, RWTH AachenUniversity, R.Mergl Aachen, Germany DepartmentofPsychiatry, UniversityofLeipzig, Leipzig, Germany G.F. Koob Committee on theNeurobiology of Addictive T.Mu¨ller Disorders, TheScrippsResearch Institute, LaJolla, DepartmentofNeurology, St. Josef Hospital, Ruhr CA, USA UniversityBochum,Bochum, Germany M. Kosel J.Mun˜oz-Moreno Departmentof Psychiatry,University ofBonn, Bonn, Fundacio´ Lluita Contra laSIDA, Hospital Universitari Germany Germans Trias i Pujol, Badalona,Spain xiv CONTRIBUTORS H.A. Nasrallah K.J.Ressler Department ofPsychiatry,University ofCincinnati DepartmentofPsychiatryandBehavioralSciencesand College ofMedicine, Cincinnati,OH, USA Yerkes Research Center, Emory University, Atlanta, GA, USA U.M. Nater DepartmentofPsychiatryandBehavioralSciences, R.Reverte EmoryUniversitySchoolofMedicine,Atlanta,GA,USA PsychiatryDepartment, Fundacio´ Pere Matade les Terres del’Ebre, Amposta,Spain C.B. Nemeroff Department ofPsychiatryand BehavioralSciences, R.G. Robinson Leonard M.MillerSchool ofMedicine Universityof Department ofPsychiatry, Roy Jand Lucille ACarver Miami, Miami, FL, USA College of Medicine, The Universityof Iowa, Iowa City, IA, USA D.J. Nutt NeuropsychopharmacologyUnit, Centre for S. Roose Pharmacology and Therapeutics, Division of Department ofPsychiatry, College ofPhysiciansand Experimental Medicine,DepartmentofMedicine, Surgeons,Columbia University, NewYork, NY, USA ImperialCollege, London, UK B.Rothbaum P. Olgiati Department ofPsychiatry and Behavioral Sciences, Institute ofPsychiatry,University ofBologna, Emory University School ofMedicine, Atlanta, GA, Bologna,Italy USA C.M. Pariante M.Rothermundt Institute ofPsychiatry,King’s College London, Department ofPsychiatry, Universityof Muenster, London, UK Muenster, Germany C.R. Raison H.G. Ruhe´ Department ofPsychiatryand BehavioralSciences, Program for MoodDisorders AMC/De Meren, EmoryUniversitySchoolofMedicine,Atlanta, Academic Medical Centre, Universityof Amsterdam, GA, USA Amsterdam, The Netherlands M.M.Rasenick S. Rushing Departments of Physiology & Biophysicsand ClinicalResearch Scholars Program,Department of Psychiatry, UniversityofIllinois Chicago College of Psychiatry,University ofPennsylvania School of Medicine,Chicago, IL, USA,and Jesse Brown VA Medicine, Philadelphia, PA, USA MedicalCenter,Chicago, IL B.J. Sahakian G.Reeves Department ofPsychiatry, Universityof Cambridge Department ofPsychiatry,Division ofChildand School ofClinical Medicine, Addenbrooke’s Hospital, Adolescent Psychiatry,University ofMarylandSchool Cambridge, UK ofMedicine, Baltimore,MD, USA A.G. Reid S.E. Sarkstein Oxford Health NHS FoundationTrust, Specialist School ofPsychiatry and ClinicalNeurosciences, Community Addiction Service-Bucks (SCAS-B),High UniversityofWestern Australia,Perth, Australia Wycombe, UK T.Schlaepfer P. Riederer Department ofPsychiatry, Universityof Bonn, Department ofPsychiatryand Psychotherapy and NPF Germany, and Division ofPsychiatricNeuroimaging, Center of Excellence Laboratories,University of DepartmentofPsychiatry,TheJohnsHopkinsHospital, Wu¨rzburg,Wu¨rzburg,Germany Baltimore, MD, USA
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