- Email: [email protected]
415. Effects of acute metabolic stress on pituitary-adrenal axis activation in patients with schizophrenia
124S
Saturday Abstracts
BIOLPSYCHIATRY 1998;43:1S-133S
design.I: patientsfollowinghslopcridoldiscontinuation,SODactivities wereinverselyandsignificantly(P=O.0365)correlatedwiththe Scalefor Assessmentof NegativeSymptoms(SANS)scoresbutnotwithscoreson the Bunney-Hamburg (BH)psychosisrating,the BriefPsychiatricRating Scale (BPRS),or the AbnormalInvoluntaryMovementScale (AIMS). Duringthe haloperidoltreatmentperiod,however,no significantcorrelations were demonstrated.Moreover,SOD activitieswere not significantlycorrelatedwith age, age at onset,durationof illness,or days off medication.Antipsychoticdrugdiscontinuationin chronicschizophrenic patientsis often associatedwith worseningof symptoms.Releasefrom the dopsmineblockadecould result in a hyperdopaminergicstate that subsequentlyleads to increased superoxideradical production (via oxidative metabolism of dopsmirre).SOD activity is coupled with supcroxideproduction.Since positive and negative symptomsoften covary, it is likely that the worseningnegative symptomsduringthe drug-freeconditionpermittedthe underlyingrelationshipbetweenSOD activityand negativesymptomsto emerge.These findingslend further supportto the notionthat oxidstivestress may contributeto the deficit syndromein schizophrenia.(Supportedby the Gflice of Research & Development,Departmentof VeteransAffairs)
413. CLINICAL IMPLICATIONS OF LIPID PEROXIDATION IN SCHIZOPHRENIA S. Mille#, B. Nguyenl’2,L.S. Mill< D.R. Evrtt’tsl’2, & S.P. Mahadikl’2 ITheVA MedicrdCenter,Augusta,GA 30904;W MedicalCollege of Georgia,,Augusta,GA; 3Universityof Georgia,,Athens,GA Severalbiologicaltheorieshavebeenproposedto explainthe etiopathophysiologyand psychopathologyof schizophrenia.Evidence is now increasingto supporta possible contributionof preferentialneuronal peroxidativedamage owing to increased “oxidativestress” (i.e., increased generationof reactive oxygenspecies (ROS) and/or impaired cellular antioxidantdefense)in schizophrenia.Neuronal(plrospholipid, proteinand DNA)peroxidativedamagecan affect the neurotrsnsrnitter receptor-mediatedsignaltransduction,enzymeactivityand geneexpressionwhichare consideredin schizophrenia.We havehere examinedthe relationshipbetweenthe levels of plasma lipid peroxidesand various dimensionsof psychopathology.levels of plasma lipid peroxideshave beengenerallyconsideredto be a reliableperipheralindexfor increased lipid peroxidationin the brain since brain is preferentiallyenrichedin lipidsthat are susceptiblefor peroxidation. Thixtypatients(mrde,ages 18-55of anyethnicorigin)withthe diagnosis of schizophreniawere thoroughlyevaluated on a large battery of neuropsychologicaltests (e.g., BPRS;Simpson-Angus,AIMS, MMSE etc.). Five milliliters(ml)of bloodwas drawnandplasmawas collected by centrifugation.The levels of lipid peroxides (nmoleshnl) were determinedby a conventionalassay for thiobarbituricacid reactive substances(TBARS).The levels of plasma TEARS were correlated positivelywith the conceptualdisorganization(P=< O.069),and negatively with the chlorpromazinedose (P=O.03)and with memorydysfunction(P=O.006).Therewas also a trendfor the antioxidanteffectof atypicalneuroleptics. These data suggestthat lipid peroxidationprobablyaffects the neurotransmitterfunctionand therebyaffectdifferentiallyvariousdimensions of psychopathologyas a function of the stage (acute vs chronic) of schizophreniaillness. Earlier we have foundthat the levels of TBARS were lower in patients with dementiacomparedto withoutdementia probablyindicatingthat patientswithdementiahavedecreasedlevelsof substrates,e.g.,essentialpolyunsaturatedfattyacids(EPUFAS),whichis consistentwiththe publishedreports.Sinceoxidstivedamageis prevent-
ableand 10SS of EPUFAsis correctable,understandingof therole of lipid peroxidstionin the psychopathologymay help to develop innovative therapeuticapproaches.
414. SCHIZOTYPAL SYMPTOMS IN FAMILIAL, CLINICAL AND COMMUNITY SAMPLES R. Toomeyl’2’3,M.J. Lyonsl’2’3,F.O. Buchtingl, K. Koenenl, S.V. Faraone2’3& M.T. Tsuang2’3 IBostonUniversityPsychologyDept.,Boston,MA 02215‘Harvard Instituteof PsychiatricGenetics,Boston,MA 021153HsrvardMedicrd SchoolDept. of Psychiatryat MassachusettsMentalHealthCenter, Boston,MA 02115and Brcdton/West RoxburyVA MedicalCenter. Brockton,MA 02401 We examinedschizotypalsymptomsand otherpersonalitytraits in four experimentalgroupsanda groupof normalcontrols.Twogroupsof first degree relatives were ascertainedthroughfamily studies: one sample related to schizophrenicpatients and the other related to affective disorderedpatients.We also aamrtaineda aarnpleof subjectspreviously hospitalizedwithborderlinepersonalitydisorder.Finally,we ascertained a sample of symptomaticvolunteerswho respondedto a newspaper advertisementseekingpeoplewith schizotypafsymptoms.All subjects wereadministeredthe StructuredInterviewfor Schizotypy.Additionally, subjectstilledouttwopcrsonrdityquestionnaires:shortformsof theNEO and MMPI.All groupsendorsedsome schizotypslsymptomsand some subjectsin each groupmet criteriafor schizotypalpersonalitydisorder. However, different patterns of symptoms emerged in the different groups.For example,whilethe borderlinesubjectsendorsedthe greatest numberof schizotypalsymptoms,the symptomaticvolunteersweremore likelyto endorsecertainpositivesymptoms,andthe relativeswere more likely to endorse certain negative symptoms.Groupsalso differed on some general personalitycharacteristics(e.g., symptomaticvolunteers demonstratedmore openness).We will report results on how groups comparedon the typicalWI profilefor schizotypy,as this profilehas been used by others to identify schizotypsl subjects, and on the relationshipbetweenschizotypalsymptomsand otherpersonalitytraits. In conclusion,differentmethodsof ascertaininggroupswithscfrizotypal symptomsgenerateddistinctconstellationsof symptomsandpersonality traits. Thesefindingsare discussedin terms of implicationsfor past and future studiesof schizophreniaspectrumcharacteristics.
415. EFFECTS OF ACUTE METABOLIC STRESS ON PITUITARY-ADRENAL AXIS Activation IN PATIENTS WITH
SCHIZOPHRENIA
I. Elmanl’2, D.R. Gastfriendl, C.M. Adle#, A.K. Malhotra2, C. Bi~, D. pick~ & A. Breie# ‘MassachusettsGeneralHospital,HarvardMedicsfSchool,Boston, MA ZExpcrimm@TherapeuticsBranch,Nationalhstitute of Mend Health,Bethesda,MD Althoughseverallines of evidencesuggestthat stms pkaysa role in the courseof schizopfueti studiesthathaveassessedstress-relevantneurobiologicalparametershave not producedconsistentmwdts.We examined effects of acute metaboficstress inducedby 2-deoxy-D-@coscon the pituitmy-adrenalaxis activation.Sixteen schizophrenicpatients and 11
SaturdayAbstracts
healthycontrolswereadministeredpbamlacoIo@caf dosesof 2DGandtheir arterial plasma was assayedfor levels of adrenocorticotropic hormone (ACTH)and cortisol.2DGinducedsignificantincma.w in the measured hormonesinbothgroupsandACfH elevationsweresignificantlygreaterin patientsthanin controls.Thesefindingsindicatethatschizophrenic patients havean exaggeratedACTHresponseto acutemetabolicstressexposure.
416. NEUROPATHOLOGICAL CORRELATES OF AUDITORY EVENTRELATED POTENTIALS IN RECENTONSET SCHIZOPHRENIA D. Umbrichtl’2, R. Bilde#, H. WU2,D. Javitt3 & J. Kane2 IPsychiatricUniversityHospitalZurich,ResearchDepartment,PO Box 68, 8029Zurich,Switzerland‘HillsideHospital,Research Depmtment,Glen Osks, NY 11004;3NatharrKlineInstitutefor PsychiatricResearch,Orangeburg,NY 10972 chronic schizophrenicpatientsshow deficientgenerationof the eventrelatedpotentialsmismatchnegativity(MMN),N2 and P3(MIelicitedin auditory‘oddball’paradigms.These abnormalitieshave been associated with neuroanatornical abnormalitiesin the right superiortemporalplane (h’fMN)andleftsupedortemporalgyms(P3).Weareperforminga studyto replicatethesefindingsin recent-onsetpatientsparticipatingin a studyof first-episodeschizophrenia. ERPsareobtainedinpassiveandactiveauditory ‘oddball’paradigms.HighresolutionMRimagesof the brainare acquired on a 1.5TGE HorizonEchoSpeedsystem(3D Fast SPGRwithII? Prep sequence;Coronalacquisition,TR = 14.5rns,TE=5.5ms,Tf=600rns,slice thickness=1.5mm).Datahavebeenobtainedin 18schizophrenicpatierm (m/f= 15/3;age = 23.8t 5.1;durationof ilfness1.3~2.2y) and9 normal controls(rn/f=5/4;age = 34.* 6.7).Forpreliminaryanalysesgreyrnati volumesof bothposteriorsuperiortemporalgyri (PST@weremeasured. Aftcrcovaryingfortheagedifferencepatientsshowedsmaoerarnplitudes of N2 andP3 thannormalcontrols,but not significantlydifferentvolumesof bothpSTGs.Amplitudesof MMN,N2andP3didnotcorrelatewithPSTG grey mattervolumes.Theseresultssuggestfirstfythat the observedERP abnormalities- comparableto those seen in chronicpatients- are not abnormalitiesandsecondlythat explainedby macroscopicneuroanatomical the correlationsreportedin samplesof chronicpatientsmaybe a mrmifestationof illnesschrmricityand/orseverity.In ourpresentationmoredetailed analysesusingseparatevolumesof Hescfd’sgyri and superiortemporal planeswilfbe provided.
417. AUDITORY EVENT-RELATED POTENTIALS (ERP) IN FIRST EPISODE AND CHRONIC SCHIZOPHRENIA D. Umbrichtl, D. Javitt2, J. Bates3, S. Pollak3, J. Lieberman4 & J. Kane3 IPsychiatricUniversityHospitalZurich,ResearchDepartment,PO Box 68, 8029Zurich,Switzerland‘NathanKlineInstitutefor Psychiatric Research,Orangebnrg,NY 109723HillsideHospital,Research Department,GlenOaks,NY 11004;4Department of Psychia@y, Universityof NorthCarolinaat ChapelHill,ChapelHill,NC 27599 Abnormalitiesof auditoryERPs,irrparticularmismatchnegativity(MMN) and P3, have beerrrepeatedlydescrlwd in chroNcschizophrenia.Some smdieshave shownassociationswith structuralabnormalitiesin specific corticalareas.‘firelackofERPdatafrompatientsat illnessonsethasleftthe questionunansweredwhetherthe neuropathology assumedto underliethe
BIOLPSYCHIATRY 1998;43:1S–133S
125S
ERP abnormalitiesis preexistingor possiblydue to neurodegenerative processesasseeiatedwith illnessprogression.We have recoded auditory ERPs(mismatchnegativity(MMN),N2andP3)irr44 patientsparticipating in a studyof firstepisodeschizophrenia,12chronicschizophrenicpatients takingpartin a clozapinestudy(age=36.5t7.l;rn/f=10/2) and 19normal controls(age:33.1t6.3 y; rdf= 14/4).26 of the frrstepisodepatientswere assessed witbin 12 months of tirst admission(=recerrt onset group; age=23.8~5.3;m/f=20/6), 17 within2 to 5 years (= fol.!ow-upgroup; age=32.0*7.3;rn/f=10/7).All patientgroupsshowedsignificantlysmaller N2 rmdP3 amplitudesthanthe controls.MMNwasreducedin the chronic patients,but not the frrst episodestudy patients.However,subdividing patientsaccordingto severityof illnesswe foundthat in the recentonset grouppatientzwithless severeformsof illnessdid not showsignificantly differentN2andP3amplitudesthannormalcontrols,whilein thefollow-up grouppatientsin both categoriesshowedabnormalitiesof these ERPs. Dccrmws of N2 amplitudewere significantlyassociatedwith illness duration.OurtindirrgsdemonstrateERPabnormalitiessuggestiveof preexistingneuropathology in temporoparietalassociationcortexin padentsat illness onset, but also provide some evidencethat is consistentwith neurndcgenerative diseasemodels.
418. MEASURING PERSEVERATIONS IN SCHIZOPHRENIA PATIENTS W. Perry & D. Braff Universityof California,San Diego,Departmentof Psychiatry Perseverationshavebeenassociatedwithfrontallobeimpairmentandare often observedamong schizophreniapatients.We assessed perseverations in schizophreniapatients (N = 71) using the WisconsinCard SortingTest (WCST)and a new Rorschachperseverationscale which yieldsthreeperseverationsubscoresanda total score.We alsocompared the resultsof the schizophreniapatientswitha normalcomparisongroup (N = 71). We found that schizophreniapatients demonstrateda high number of perseverationson both the WCST and the Rorschach perseverationscale whencomparedto the normafcomparisonsubjects. Among schizophreniapatients, WCST perseverative responses was significantlycorrelatedwith Rorschach-derivedstuck-in-setperseverations, WAIS-RVocabukuyscores and negative symptomratings. No signiflcarrtdifferencesin any of the measures of perseverationwere found to be associatedwith diagnostic subtype.Finally, WCST and Rorschach measures for the schizophreniaand normal comparison participantswere entered into a logistic regression.The WCST total errors and the three Rorschachperseverationmeasuresresulted in the correct classificationof 89.4%of the total cases, with a sensitivityof 91%,specificityof 91%and positivepredictivepowerof 87.8%.These data provideevidencethat perseverativebehavioris widelyobservedin schizophreniapatientsusing a varietyof instruments.The authorswill discuss the benefit of using multiple measures of perseverationin schizophreniaresearch.
419. FURTHER EVIDENCE OF PREFRONTAL DYSFUNCTION IN SCHIZOPHRENIA: ANTISACCADE AND WCST PERFORMANCE IN ACUTE AND REMITTED SCHIZOPHRENIA AND FIRST DEGREE RELATIVES C.E. Curtis, K.J. Feil & W.G. Iacono Departmentof Psychology,Universityof Minnesota,MinneapolisMN 55455 Increasingevidenceimplicatesdysfunctionof the prefrontal cortex as an importantfactor in the pathologyof schizophrenia.In the current
Saturday Abstracts
BIOLPSYCHIATRY 1998;43:1S-133S
design.I: patientsfollowinghslopcridoldiscontinuation,SODactivities wereinverselyandsignificantly(P=O.0365)correlatedwiththe Scalefor Assessmentof NegativeSymptoms(SANS)scoresbutnotwithscoreson the Bunney-Hamburg (BH)psychosisrating,the BriefPsychiatricRating Scale (BPRS),or the AbnormalInvoluntaryMovementScale (AIMS). Duringthe haloperidoltreatmentperiod,however,no significantcorrelations were demonstrated.Moreover,SOD activitieswere not significantlycorrelatedwith age, age at onset,durationof illness,or days off medication.Antipsychoticdrugdiscontinuationin chronicschizophrenic patientsis often associatedwith worseningof symptoms.Releasefrom the dopsmineblockadecould result in a hyperdopaminergicstate that subsequentlyleads to increased superoxideradical production (via oxidative metabolism of dopsmirre).SOD activity is coupled with supcroxideproduction.Since positive and negative symptomsoften covary, it is likely that the worseningnegative symptomsduringthe drug-freeconditionpermittedthe underlyingrelationshipbetweenSOD activityand negativesymptomsto emerge.These findingslend further supportto the notionthat oxidstivestress may contributeto the deficit syndromein schizophrenia.(Supportedby the Gflice of Research & Development,Departmentof VeteransAffairs)
413. CLINICAL IMPLICATIONS OF LIPID PEROXIDATION IN SCHIZOPHRENIA S. Mille#, B. Nguyenl’2,L.S. Mill< D.R. Evrtt’tsl’2, & S.P. Mahadikl’2 ITheVA MedicrdCenter,Augusta,GA 30904;W MedicalCollege of Georgia,,Augusta,GA; 3Universityof Georgia,,Athens,GA Severalbiologicaltheorieshavebeenproposedto explainthe etiopathophysiologyand psychopathologyof schizophrenia.Evidence is now increasingto supporta possible contributionof preferentialneuronal peroxidativedamage owing to increased “oxidativestress” (i.e., increased generationof reactive oxygenspecies (ROS) and/or impaired cellular antioxidantdefense)in schizophrenia.Neuronal(plrospholipid, proteinand DNA)peroxidativedamagecan affect the neurotrsnsrnitter receptor-mediatedsignaltransduction,enzymeactivityand geneexpressionwhichare consideredin schizophrenia.We havehere examinedthe relationshipbetweenthe levels of plasma lipid peroxidesand various dimensionsof psychopathology.levels of plasma lipid peroxideshave beengenerallyconsideredto be a reliableperipheralindexfor increased lipid peroxidationin the brain since brain is preferentiallyenrichedin lipidsthat are susceptiblefor peroxidation. Thixtypatients(mrde,ages 18-55of anyethnicorigin)withthe diagnosis of schizophreniawere thoroughlyevaluated on a large battery of neuropsychologicaltests (e.g., BPRS;Simpson-Angus,AIMS, MMSE etc.). Five milliliters(ml)of bloodwas drawnandplasmawas collected by centrifugation.The levels of lipid peroxides (nmoleshnl) were determinedby a conventionalassay for thiobarbituricacid reactive substances(TBARS).The levels of plasma TEARS were correlated positivelywith the conceptualdisorganization(P=< O.069),and negatively with the chlorpromazinedose (P=O.03)and with memorydysfunction(P=O.006).Therewas also a trendfor the antioxidanteffectof atypicalneuroleptics. These data suggestthat lipid peroxidationprobablyaffects the neurotransmitterfunctionand therebyaffectdifferentiallyvariousdimensions of psychopathologyas a function of the stage (acute vs chronic) of schizophreniaillness. Earlier we have foundthat the levels of TBARS were lower in patients with dementiacomparedto withoutdementia probablyindicatingthat patientswithdementiahavedecreasedlevelsof substrates,e.g.,essentialpolyunsaturatedfattyacids(EPUFAS),whichis consistentwiththe publishedreports.Sinceoxidstivedamageis prevent-
ableand 10SS of EPUFAsis correctable,understandingof therole of lipid peroxidstionin the psychopathologymay help to develop innovative therapeuticapproaches.
414. SCHIZOTYPAL SYMPTOMS IN FAMILIAL, CLINICAL AND COMMUNITY SAMPLES R. Toomeyl’2’3,M.J. Lyonsl’2’3,F.O. Buchtingl, K. Koenenl, S.V. Faraone2’3& M.T. Tsuang2’3 IBostonUniversityPsychologyDept.,Boston,MA 02215‘Harvard Instituteof PsychiatricGenetics,Boston,MA 021153HsrvardMedicrd SchoolDept. of Psychiatryat MassachusettsMentalHealthCenter, Boston,MA 02115and Brcdton/West RoxburyVA MedicalCenter. Brockton,MA 02401 We examinedschizotypalsymptomsand otherpersonalitytraits in four experimentalgroupsanda groupof normalcontrols.Twogroupsof first degree relatives were ascertainedthroughfamily studies: one sample related to schizophrenicpatients and the other related to affective disorderedpatients.We also aamrtaineda aarnpleof subjectspreviously hospitalizedwithborderlinepersonalitydisorder.Finally,we ascertained a sample of symptomaticvolunteerswho respondedto a newspaper advertisementseekingpeoplewith schizotypafsymptoms.All subjects wereadministeredthe StructuredInterviewfor Schizotypy.Additionally, subjectstilledouttwopcrsonrdityquestionnaires:shortformsof theNEO and MMPI.All groupsendorsedsome schizotypslsymptomsand some subjectsin each groupmet criteriafor schizotypalpersonalitydisorder. However, different patterns of symptoms emerged in the different groups.For example,whilethe borderlinesubjectsendorsedthe greatest numberof schizotypalsymptoms,the symptomaticvolunteersweremore likelyto endorsecertainpositivesymptoms,andthe relativeswere more likely to endorse certain negative symptoms.Groupsalso differed on some general personalitycharacteristics(e.g., symptomaticvolunteers demonstratedmore openness).We will report results on how groups comparedon the typicalWI profilefor schizotypy,as this profilehas been used by others to identify schizotypsl subjects, and on the relationshipbetweenschizotypalsymptomsand otherpersonalitytraits. In conclusion,differentmethodsof ascertaininggroupswithscfrizotypal symptomsgenerateddistinctconstellationsof symptomsandpersonality traits. Thesefindingsare discussedin terms of implicationsfor past and future studiesof schizophreniaspectrumcharacteristics.
415. EFFECTS OF ACUTE METABOLIC STRESS ON PITUITARY-ADRENAL AXIS Activation IN PATIENTS WITH
SCHIZOPHRENIA
I. Elmanl’2, D.R. Gastfriendl, C.M. Adle#, A.K. Malhotra2, C. Bi~, D. pick~ & A. Breie# ‘MassachusettsGeneralHospital,HarvardMedicsfSchool,Boston, MA ZExpcrimm@TherapeuticsBranch,Nationalhstitute of Mend Health,Bethesda,MD Althoughseverallines of evidencesuggestthat stms pkaysa role in the courseof schizopfueti studiesthathaveassessedstress-relevantneurobiologicalparametershave not producedconsistentmwdts.We examined effects of acute metaboficstress inducedby 2-deoxy-D-@coscon the pituitmy-adrenalaxis activation.Sixteen schizophrenicpatients and 11
SaturdayAbstracts
healthycontrolswereadministeredpbamlacoIo@caf dosesof 2DGandtheir arterial plasma was assayedfor levels of adrenocorticotropic hormone (ACTH)and cortisol.2DGinducedsignificantincma.w in the measured hormonesinbothgroupsandACfH elevationsweresignificantlygreaterin patientsthanin controls.Thesefindingsindicatethatschizophrenic patients havean exaggeratedACTHresponseto acutemetabolicstressexposure.
416. NEUROPATHOLOGICAL CORRELATES OF AUDITORY EVENTRELATED POTENTIALS IN RECENTONSET SCHIZOPHRENIA D. Umbrichtl’2, R. Bilde#, H. WU2,D. Javitt3 & J. Kane2 IPsychiatricUniversityHospitalZurich,ResearchDepartment,PO Box 68, 8029Zurich,Switzerland‘HillsideHospital,Research Depmtment,Glen Osks, NY 11004;3NatharrKlineInstitutefor PsychiatricResearch,Orangeburg,NY 10972 chronic schizophrenicpatientsshow deficientgenerationof the eventrelatedpotentialsmismatchnegativity(MMN),N2 and P3(MIelicitedin auditory‘oddball’paradigms.These abnormalitieshave been associated with neuroanatornical abnormalitiesin the right superiortemporalplane (h’fMN)andleftsupedortemporalgyms(P3).Weareperforminga studyto replicatethesefindingsin recent-onsetpatientsparticipatingin a studyof first-episodeschizophrenia. ERPsareobtainedinpassiveandactiveauditory ‘oddball’paradigms.HighresolutionMRimagesof the brainare acquired on a 1.5TGE HorizonEchoSpeedsystem(3D Fast SPGRwithII? Prep sequence;Coronalacquisition,TR = 14.5rns,TE=5.5ms,Tf=600rns,slice thickness=1.5mm).Datahavebeenobtainedin 18schizophrenicpatierm (m/f= 15/3;age = 23.8t 5.1;durationof ilfness1.3~2.2y) and9 normal controls(rn/f=5/4;age = 34.* 6.7).Forpreliminaryanalysesgreyrnati volumesof bothposteriorsuperiortemporalgyri (PST@weremeasured. Aftcrcovaryingfortheagedifferencepatientsshowedsmaoerarnplitudes of N2 andP3 thannormalcontrols,but not significantlydifferentvolumesof bothpSTGs.Amplitudesof MMN,N2andP3didnotcorrelatewithPSTG grey mattervolumes.Theseresultssuggestfirstfythat the observedERP abnormalities- comparableto those seen in chronicpatients- are not abnormalitiesandsecondlythat explainedby macroscopicneuroanatomical the correlationsreportedin samplesof chronicpatientsmaybe a mrmifestationof illnesschrmricityand/orseverity.In ourpresentationmoredetailed analysesusingseparatevolumesof Hescfd’sgyri and superiortemporal planeswilfbe provided.
417. AUDITORY EVENT-RELATED POTENTIALS (ERP) IN FIRST EPISODE AND CHRONIC SCHIZOPHRENIA D. Umbrichtl, D. Javitt2, J. Bates3, S. Pollak3, J. Lieberman4 & J. Kane3 IPsychiatricUniversityHospitalZurich,ResearchDepartment,PO Box 68, 8029Zurich,Switzerland‘NathanKlineInstitutefor Psychiatric Research,Orangebnrg,NY 109723HillsideHospital,Research Department,GlenOaks,NY 11004;4Department of Psychia@y, Universityof NorthCarolinaat ChapelHill,ChapelHill,NC 27599 Abnormalitiesof auditoryERPs,irrparticularmismatchnegativity(MMN) and P3, have beerrrepeatedlydescrlwd in chroNcschizophrenia.Some smdieshave shownassociationswith structuralabnormalitiesin specific corticalareas.‘firelackofERPdatafrompatientsat illnessonsethasleftthe questionunansweredwhetherthe neuropathology assumedto underliethe
BIOLPSYCHIATRY 1998;43:1S–133S
125S
ERP abnormalitiesis preexistingor possiblydue to neurodegenerative processesasseeiatedwith illnessprogression.We have recoded auditory ERPs(mismatchnegativity(MMN),N2andP3)irr44 patientsparticipating in a studyof firstepisodeschizophrenia,12chronicschizophrenicpatients takingpartin a clozapinestudy(age=36.5t7.l;rn/f=10/2) and 19normal controls(age:33.1t6.3 y; rdf= 14/4).26 of the frrstepisodepatientswere assessed witbin 12 months of tirst admission(=recerrt onset group; age=23.8~5.3;m/f=20/6), 17 within2 to 5 years (= fol.!ow-upgroup; age=32.0*7.3;rn/f=10/7).All patientgroupsshowedsignificantlysmaller N2 rmdP3 amplitudesthanthe controls.MMNwasreducedin the chronic patients,but not the frrst episodestudy patients.However,subdividing patientsaccordingto severityof illnesswe foundthat in the recentonset grouppatientzwithless severeformsof illnessdid not showsignificantly differentN2andP3amplitudesthannormalcontrols,whilein thefollow-up grouppatientsin both categoriesshowedabnormalitiesof these ERPs. Dccrmws of N2 amplitudewere significantlyassociatedwith illness duration.OurtindirrgsdemonstrateERPabnormalitiessuggestiveof preexistingneuropathology in temporoparietalassociationcortexin padentsat illness onset, but also provide some evidencethat is consistentwith neurndcgenerative diseasemodels.
418. MEASURING PERSEVERATIONS IN SCHIZOPHRENIA PATIENTS W. Perry & D. Braff Universityof California,San Diego,Departmentof Psychiatry Perseverationshavebeenassociatedwithfrontallobeimpairmentandare often observedamong schizophreniapatients.We assessed perseverations in schizophreniapatients (N = 71) using the WisconsinCard SortingTest (WCST)and a new Rorschachperseverationscale which yieldsthreeperseverationsubscoresanda total score.We alsocompared the resultsof the schizophreniapatientswitha normalcomparisongroup (N = 71). We found that schizophreniapatients demonstrateda high number of perseverationson both the WCST and the Rorschach perseverationscale whencomparedto the normafcomparisonsubjects. Among schizophreniapatients, WCST perseverative responses was significantlycorrelatedwith Rorschach-derivedstuck-in-setperseverations, WAIS-RVocabukuyscores and negative symptomratings. No signiflcarrtdifferencesin any of the measures of perseverationwere found to be associatedwith diagnostic subtype.Finally, WCST and Rorschach measures for the schizophreniaand normal comparison participantswere entered into a logistic regression.The WCST total errors and the three Rorschachperseverationmeasuresresulted in the correct classificationof 89.4%of the total cases, with a sensitivityof 91%,specificityof 91%and positivepredictivepowerof 87.8%.These data provideevidencethat perseverativebehavioris widelyobservedin schizophreniapatientsusing a varietyof instruments.The authorswill discuss the benefit of using multiple measures of perseverationin schizophreniaresearch.
419. FURTHER EVIDENCE OF PREFRONTAL DYSFUNCTION IN SCHIZOPHRENIA: ANTISACCADE AND WCST PERFORMANCE IN ACUTE AND REMITTED SCHIZOPHRENIA AND FIRST DEGREE RELATIVES C.E. Curtis, K.J. Feil & W.G. Iacono Departmentof Psychology,Universityof Minnesota,MinneapolisMN 55455 Increasingevidenceimplicatesdysfunctionof the prefrontal cortex as an importantfactor in the pathologyof schizophrenia.In the current