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A pet study of word generation in obligate carriers of the predisposition to schizophrenia

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A pet study of word generation in obligate carriers of the predisposition to schizophrenia
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  4 1 THE EFFECT OFANATYPICALANTIPSYCHOTIC RISPERIDONE ON TEMPORAL LOBEANDPREFRONTAL CORTEX ACTIVITYINSCHIZOPHRENIA Andrew M. Speer, S. Craig Risch, Mark B. Hamner, Monica Molloy,Helen G. Ulmer, C. Lindsay De Vane, Diana J.Vincent, Mark S. George Departmento Ps ychiatry M  U S  C J71AshleyAvenue Charleston SC 2942J. USA Background: Functionalbrainimagingfindingsinschizo phrenia havebeeninconsistent.Althoughtheylargelysupportmesolirnbichyperperfusionandfrontalhypoperfusiondefects,variabilityintheliteraturemayrepresentillnessprogressionorheterogeneityofpathogenesis.Neuro-cognitivetasksthatinvolveactivationofthetemporallobesandprefrontalcortexhavebeenreportedtoworsenhypoperfusioninschizophrenicpatientscomparedtonormals.WehavedesignedastudyusingechoplanarBOLDfMRIduringaverballluencytasktodirectlyexplorethesequestions. Methods : Patientswithschizophrenia matchedforage,gender,level of educationandseverity of illness willbeimagedatrestandduringaverballluencytask.Eachpatientisinitiallybeingscannedinamedication-freestate  4-7 daysduration and thenfollowing6weeksonafixeddose of eitherhaloperidol  N = 10at6-12mg/d ,risperidone N = 10at 4-8 mg/d orclozapine N = 5 at300-400mg/d .ClinicalresponseismeasuredbyserialPANSSand em ratings.10healthyvolunteers are beingseriallyscannedforcomparison. Results: Todate,wehavescanned20medication-freeschizophrenicpatientsandre-scanned3ofthesepatientsat6weeksfollowingtreatmentwithanatypicalantipsychoticagent.Wewillcomparetheextentthatrisperidoneandclozapinenormal ize prefrontalcortexfunctionatrestandactivationtohaloperidol.Wehypothesizethatthedegreeofprefrontalnormalization will correlatewithclinicalimprovement.•Acknowledgments:NARSAD,TheStanleyFoundation,JanssenPharmaceuticals   A PET STUDYOFWORDGENERATIONINOBLIGATECARRIERSOFTHEPREDISPOSITIONTOSCHIZOPHRENIA Sean A.Spence, TonmoySharma, Jonathan HelIewelI, Martin Stefan,PaulGrasby, Bill Deakin, Robin Murray, ChrisFrith,PeterLiddle MRC CyclotronUnit HammersmithHospital DuCaneRoad LondonWJ2OHS Buildingonpreviouslyreportedfindingsofaqualitativelydifferentanatomyunderlyingwordgenerationinchronicandacute drugnaive schizophrenicsandnormalindividualswe  7 havestudiedpresumedobligatecarriers of thepredispositiontoschizophrenia.Theseindividualsaredrawnfrommultiplyaffectedkindredsbutarethemselvesclinicallyunaffected.WehaveusedPETtomeasureregionalcerebralbloodflow rCllF in10obligatesand10normalcontrols controllingforage.sex,andverbalIQ .SubjectswerescannedwhilearticulatingwordsprovidedbytheexperimenteratarateofIevery5s,andalsowhilearticulatingself-generatedwordsatthesamerate.ThedifferenceinrCBFbetweenthetwoconditionsindicatesthepattern of cerebralactivityassociatedwithwordgeneration.Obligatesdemonstrateafocalfailureofactivationinleftmedialfrontallobe BrodmannArea6/8 .Thesefindingsareconsistentwiththeoriesimplicatingaheritablecomponenttothebraindysfunctionseeninschizophrenia. 4 I ALTEREDLATERALISATIONOFAUDITORYCORTICALRESPONSETOEXTERNALSPEECHINSCHIZOPHRENIA Peter W .R . Woodruff, Ian C. Wright, Michael Brammer,Edward T. Bullmore, RobertHoward, Anthony S. David, Jane Shapleski, Susan Rossell. Chris Andrew,Steven C.R .Williams, Robin M. Murray Department   PsychologicalMedicine Institute of Psychiatry Denmark   London SEJ SAp UK FunctionalMRIhasbeenusedongroupdatatodemonstratethatauditoryhallucinationsalterthepatternofauditorycortexactivationinresponsetoexternalspeech  I .Dopatientswithschizophreniaexhibitalteredlaterality in theirresponsetoexternalspeech7Eightschizophrenics DSM-IV [not activelyhallucinating withameanage36.0werecomparedwitheighthealthycontrols meanage35.1 [allright-handedmales .Subjectswerepresentedwithalternating40sepochs of speechbinaurallyandblanktapewhilstbeingscanned.Brainactivationmapsfromeachgroupweretransformedintostandardisedspaceandmedianimagesconstructed.Voxelsrepresentingthedifferencebetweenmedianimagesinthe2groupswerecomputed  p<0 .002 .Therewassignificantly greater activationinrightmiddletemporalgyrus llA21 and less activationinleftposteriorauditorycortex BA22 intheschizophrenicthanhealthycontrolgroup..Processing of externalspeechinschizophreniaappearstobebiasedtowardsrightauditorycortex regionsthoughttobeinvolvedinprosodicperception .Thisright-sidedshiftmaybeduetoabnormalintrinsicwiringoftheauditorysystemoranasymmetricattentionaleffectonsensorycortexinschizophrenia.References   WoodruffP.W.R.,WrightI,etal.,Neurolrnage,1996, 3,3, s522.
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