37. Diffusion tensor imaging of white matter tracts in schizophrenia

37. Diffusion tensor imaging of white matter tracts in schizophrenia

Thursday Abstracts clinicalsymptomsof scbizophn-mia spectmmillness.The identificationof psychophysiologicrd measuresthatare moresensitiveto the subtl...

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Thursday Abstracts

clinicalsymptomsof scbizophn-mia spectmmillness.The identificationof psychophysiologicrd measuresthatare moresensitiveto the subtlepsychopathologyof schizophreniaspectrumsubjectscouldprovide“target”intermediate phenotypesand thus add power to genetic linkage analyses. Prepulaeinhibition(PPI)of the startlereflex(SR)is anoperationalrneaame of Serrsorim otor gating.Sehiz.ophmrric patientaas well as individualswitb dizotypal personalitydisordershowreducedinhibitionof the SR when startlestimuliare precededby weakprestinndi.In addition,schizophrenic patientashow impairedhabituationof the SR, with a less than normal reductionof SRmagnitudeoverrepeatedpresentationsof startlingstimuli. We hypothesizedthat relativesof schir.ophrerric patientswouldalso abow PPIdeficitsreflectingtrait-linkeddeficitsin centralinhibition.We assessed 7 Wrizophrcnicprobands,21 of theirrelativesand 10normalcomparison subjectsin a startleparadigmthatprovidedmeasuresof PPIandhabituation of theSR.BoththeprobandsandtheirrelativeshadreducedPMat 30maw (effectsize = 2.0)and 120rnaec(effectsim = 0.8)interstimulusintervals. HabituationoftheSRbetweenthelirst andsecondblockof sfirnuliwasalso reducedin probands(15%, effect size=l.4) and relatives(33%,effect size=O.6)comparedto normalswhohada 47%reductionin SRmagnitude. “atephen~ Thesedata suggestthatPPIandhabituationareusefulintermedr @s of schizophreniaspectrumillness with potentialutilityin genetic linkageanalyses.

34. WORKING MEMORY AND SCHIZOPHRENIA W. Perry & D. Braff Universityof California,San Diego,Departmentof Psychiatry Workingmemoryhasbeerrdescribedas a brainsysteminvolvingtemporary storageandmanipulationof information.Schizophrenia patientahavebeen reportedto haveimpairedperformanceon workingmemorytasks.Selriw phreniapatientsandnormalcomparisonsubjectsweretestedona visuoapatial and an auditoryworkingmemorytask. Groupdifferenceson these measureswere assessed.Test @ormau @ was eonvdatedWitbverbal intelligenceandsymptomfactorscores.Visuospatialandauditoryworking memoryperformancewere cormktcd with each other and both were impairedin schizophrenia patientscomparedto thenormalsubjects.Preliminary resultssuggesttbat amongthe aehizophrerria patienta,lowerv.3bsJ intelligenceandgreaternegativesymptomfactorscoreswerecorrelatedwitb impairedworkingmemoryperformance.Thesefindingssupportthehypothesis that schizophreniapatienfihave impairedviauoapatialand auditory workingmemoryand suggeststhat verbal intelligence,althoughhighly correlatedwith workingmemoryperformance,is not responsiblefor the meaningtldrelationshipbetweenworkingmemoryand symptoms.The relationshipbetweenworkingmemorydeficitsandnegativesymptomsadds supprt forfrontalcortexdysfunctionin schimpbreniapatients.Theimportanceof ident@ingwhichaspectsof workingmemoryare mostcriticalto thestudyof schizoplueniaand whichtestabestmeasurethoaepammetmare discussed.

35. NEUROPSYCHOLOGICAL PREDICTION OF FUNCTIONAL OUTCOME IN FIRST-EPISODE SCHIZOPHRENIA R.S. Goldmanl, R.M. Bilderl, E. Pappadopulosl, G. Reiterl, J. Alvirl, D. Robinsonl & J. Lieberman2 lHillsideHospital,Glen Oaks,NY 11004;‘Universityof North Carolinaat ChapelHill, NC 27599

BIOLPSYCHIATRY 1998;43:1S-133S

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followingtreatment). m y~lm~ ~= ofinw~: m rmrnory,executive,mc4m,aaeneonandvisual-sptial;smlcawemz referenced to ear controlcohort(n=36). J33ternal wale mnakncy was high for dre resultingscales(Weffmen “ talpha appmrdng .90)andcomtmctvaliditywas alsoamrn-d by mn6rmmy factoranalysisof fit indices>.90). FutwtionaloutcOnEwas aaamsedwiththe SocialAdjuatrnentScale(SAS) aammimd at 2 yeas (64 ptients had neuropychological and @cmm measums)andat5 yearn(32@ientsItXXiVdbd3setsofrneamm)following tbefirstepiwde.Meaaumaof positive,mgativeand&m@mdon aym@orm weredme lcxkedto [email protected] multiplemgreaaion analyseslm’ealeddlat integrityof altentimlalfuncdom6 monthsfollowing lmatlwntacmmtedfor the gmateatvariancein twoyeargeneraladjusmlent outcomeF(1, 55)= 6.M,p=.02;mukipleR= .32]andwasalaopmdiedveof more-veda P(1,55) = 11.7,p=.(KIl;multipleR = .42].Atthe 5 yeartirnepoirLattentional fumtiorrwasonlymodemly mmiated Wilhbetter outcome.MeasmesOfmsidualsymptomfollowinginitialtleamEntfailedto predicttwoandfiveyearoutcome.m p’eaentstudytbatattentid -m “t ~ of c~~ ~, ~ nantof sulmequent functior3al mltconwin theearlycourse

36. SENSORY “GATING IN” IN SCHIZOPHRENIA PATIENTS N. Boutrosl & R. Schlaudeckerl IYaleUniversitySchoolof Medicineand The West HavenVAMC, West havenCT 06516 A deficit in the ability to inhibit incoming irrelevant sensory input “Gating Out” has repeatedlybeen demonstratedin subjects suffering from Schizophrenia.It is likelyto be as importantthat patientsrespond properlyto morerelevantsensoryinput“GatingIn”.We havepreviously reportedthat normalsubjectsrespondto stimuluschangein mridenticrd paired-clickparadigms with a significantdecrease in the deof attenuationof the amplitudeof the secondof the two stimuliof the pair. in orderto assessthisfunctionin Schizophreniapatientswecomparedthe responses in identical-paired-clicksand un-identical-paired-clicksbetween 12 Schizophreniapatients and 12 age and sex matchednormal control subjects. While tbe ratios of the amplitudes of the second responses to the ilrat responses were much higher in Schizophrenia patients(F=28.297,P
Brain Imaging Thursday,May 28, 2:30 PM–5:00 PM, Location: Pier 3 Chairperson:KarenBerman 37. DIFFUSIONTENSOR IMAGING OF WHITE MAITER TRACTS IN SCHIZOPHRENIA K.O. Liml’2’4,M. Hedehus3, A. de Crespigny3, V. Menon2 & M. Moseley3 *VAPaloAltoHealthCareSystem,PaloAlto,CA94304;‘Department of Psychiatry,StanfoodUniversitySchoolof Medicine;3Depmtment of Radiology,StanfordUniversitySchoolof Medicine;4NathanKline Institutefor psychiatricResearch,Orangeburg,NY

The pment studyexaminedthe degm to Whichneumpsychow indices toxmnmtofthefmxepisode 2and5yearsfollowing mediatefnnetiorraloutcome Schizophrenicpatientshavebeenshownto havestructuralabnormalities “ Patientawemaaseswdwitha~~losi~ ofschim@ema batteryfollowingrmolutionof their initialpsychoticepisode(six rnondrs of the corpus callosum implyingdeficits in interhernisphericaxonal

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BIOLPSYCHIATRY 1998;43:1S-133S

comectivity.Diffusiontensor imaging(DTI)maps the degreeof directionalityof orientedwater proton anisotropicmotionsin white matter tract myelin bundles, and may be sensitiveto abnormalitiesin white matterintegrity.PatientswithDSM-IVschizophrenia(n = 8) andnormal controls (n = 6) underwenta DTI protocol,performedon a 1.5TGE SIGNAsystemusing a Pulsed GradientSpin Echo EPI techniqueand acquiring 18 oblique,AC-PCoriented,5 mm thick, skip O mm axial slices.Diffusionwas measuredalongthe six non-collineaxdirectionsand four diffusionweightedimagesacquiredand averagedfor each gradient direction. The diffusion tensor for each pixel was determined,and eigenvalues,eigenvectorsandthe FractionalArrisotropy(FA)calculated over all 18 slices. These vahreswere plottedas FA maps which were smoothed, spatially normalized to a template brain (based on six controls)in stereotacticTalairach space, and comparedacross groups usingSPM96.Oroupanalysisrevealeda significant(p<.05 c.omxtedfor multiplecomparisons)reductionin theFAin schizophrenics,prirnarilyin the corpuscallosum.This reducedfractionalanisotropyin the schizophrenics could be explainednot only by a reduced number of fiber bundles comprisingthe corpus callosum but also a disorderingof individualfibers within those bundles. Supportedby Departmentof VeteransAffairsand NIH (MH 30854,MH53313,NS35959).

38. SEASONAL VARIATIONS IN RIGHT-TOLEFT METABOLIC BALANCE IN THE PREFRONTAL CORTEX M. Bocherl’2, N. Kusubovl & T.E. Nordahll’2 ‘Center forFunctional Imaging,LBNL,Berkeley,Calif.9472Q~

Thursday Abstracts

who fall outsideof currentsyndromeboundaries.As part of a studyof childhood-onsetschizophrenia(COS), we identified a subgroup of childrenwithatypicalpsychosis,provisionallylabelled“mukidimensionally impaired”(MDI).These MDI childrendiffer from COS in king markedlyimpulsive,inattentive,emotionallylabile and in lacking the pervasivehallucinations,delusionsor thoughtdisordercharacteristicsof COS.Allof the MIXchildrenmetcriteriafor ADHD.Onthe otherhand, we have shownthat bothMDI and COSchildrenshare a similarpattern of early transient autistic features, expressiveand receptive language deficits,similarneuropsychological profileandincreasedratesof schizophrenicspectrumdisordersin first degreerelatives(Kumraet al,, 1998; submitted). Methods:Anatomicbrainmagneticresonanceimageswere obtainedfor 15patientswithmultidimensionally impairedsyndromeand35age-,sexaodheight-matchednormalcontrolswhowere scannedduringthe same timeperiod.Quantitativemeasurementswereobtainedfor the cerebrum, anteriorfrontalregion,lateral ventricles,thalamus,basal gangliastructures, corpuscallosum,temporallobe, hippocampus,and amygdala. Results:For the MDIsubjects,totalcerebralvolumeandanteriorfrontal volume were smaller (t=2.85, P=0.006 and ANCOVA, F=19.7, P= O.0001respectively);and the lateral ventricles were larger than healthycontrols(ANCOVA,F=4.11, P= O.05). Discussion:AnatomicMN brainmeasuresof childrenwith mukidimensionallyimpairedsyndromeexhibita patternof abnormalitiessimilarto that foundfor childhood-onset schizophrenia(Frazieret al., 1996)and to that repmtedfor adultschizophrenicpatients.Thesedata supportstudiescited aboveindicatinga closerelationshipbetweenMJXandschizophrenia.

CA95817 of Psychiatry, UCDavisMedicalCenter,Sacramento, The authorshave recentlyobservedseasonalvariationsof hemispheric cerebral glucosemetabolicasymmetryindex for the humanprefrontal cortex (Nordahland Cohen 1997).This PET-FDGstudy was done in normalvolunteersresidingin the east coast.Cerebralglucosemetabolic ratesof therightprefrontrdregionshowedan inclinationtobe higherthan the left in winterandlowerin summer.Thepurposeof the presentstudy, was to test the replicabilityof the abovefindingsin a small groupof normalsubjects,livingin a differentclimaticandtime-zone(westcoast, California).Methods: 18~G w= injec~d in 10 subjects (4 ‘g summerand 6 during winter), performinga Stroopmental task. PET slices were acquiredwith a high-resolution,single-slicetomographin threeplanesdefinedby an MRI.An indexof metabolichemisphericwas calculatedas the ratio of (R-L)to (R+L) for eachregion.ANOVAwas used to evaluate seasonal group differences. Results: A significant (p
39. BRAIN ANATOMIC MAGNETIC RESONANCE IMAGING IN PEDIATRIC PATIENTS WITH “MULTIDIMENSIONALLY IMPAIRED SYNDROME” S. Kumra, J.N. Giedd, S. Hamburger & J.L. Rapoport Fromthe ChildPsychiatryBranch,NationalInstituteof MentalHealth Objective:Thereis a growingrecognitionof a sizeablegroupof children withcomplexdevelopmentaldisordersandtransientpsychoticsymptoms

40. VIEWING EMOTIONAL STIMULI INCREASES SKIN CONDUCTANCE AND BLOOD FLOW IN LIMBIC BRAIN S.F. Taylorl, I. Liberzonl’2, L. Deckerl, R.A. Koeppe3 & S. Minoshima3 IUniversityof MichiganDepartmentof Psychiatry,ArmArbor,Ml 48109-0116;2AmrArborVeteransAdministntionMedicalCenter; 3Urriversityof MichiganDepartmentof InternalMedicine,Divisionof NuclearMedicine Emotionally-salientstimuli elicit peripheralautonomicrespmes, like increasesin skinconductance(SCR),whichare abnormatin psychiatric disorders,suchas schizophrenia.Evidencefromarrimrdresearchsuggests that centralcontrolof this responsearisesin the reticularformationand posteriorhypothalamus,while modulatoryinfluencesfrom emotionally salientstimuliderivefromthe amygdalaandcorticalstructures.Usingan [0-15] PET methodology,we soughtto map the peripheralautonomic responseto these predictedcentralregions.Ten healthyfemale subjects viewedslides selectedfrom the InternationalAffectivePicture System, consistingof eitheremotionallyneutralor negativevisualcontent(facial mutilation,morgue pictutvs). While viewing slides (5 sec per slide) duringeach of 8, 60 sec PET scans,subjectseither rated the seventyof the aversive content (encodingphase, scans 1-2, 7-8) or determined whetherthe imageshad been previouslypresented(recognitionphase, scans4-6).Whileencodingnegativeimages,comparedto neutralimages, subjectsexhibitedgreater SCRS,and cerebral blood flow increasedin bilateralamygdala,thalamic/hypotbakmicarea,midbrainandleft lateral prefrontalcortex.Correlationmapscalculatedfor regionalbrain activity and SCR magnitudeduring the scanning session showed significant positive correlations in the right amygdala, midbrain and thalarmd hypothalamus.While recognizingnegative images, subjects activated righ~ lateral prefrontalcortex. Recognizingnegativeimages differentially affected regional activity in the occipital cortex (greater during