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402. Neuroleptic induced dopamine D2 receptor up-regulation in schizophrenia
120s
BIOLPSYCHIATRY 1998:43 :1S-133S
outcomesandcontinuedrehospitalimtions. Appropriatedosingis impmtant becausepatientswhoareunderdnsd or whoreceiveexcessivedosesmay fail to respond,especiallyif a drug has a therapeuticwindowfor an efficaciousdose.Noncompliance may also resultsecontkuyto side effect occurrence.Thissmdyexaminedtrendarelatedto risperidonedosingwithin the state systemand detaminedrecidivismrates for thosewhohad be=en discharged.All patientstxeatedwithinan inpatientstatepsychiatricfacility were includedin this computerizeddatabase.This datasetcontains1,057 patientrecordsand reflectsrisperidoneusagepatternssimilarto national data.Meanrisperidonedoseshavedeclinedsignificmtlyeachyearsinceits introductionin bothdischargedandhmpitalizedpatients.In 1996,patients (n=449)whoweredischargedreceivedsignificantlylowerdosesthanthose remaininghospitalized(4.3 vs. 5.6 mgMay,p
400. WORD RECALL IN SCHIZOPHRENIA: A CONNECTIONIST MODEL P.G. Nestorl’2, S.J. Akdagl>2,B.F. O’Donnell, M. Niznikiewicz2, S. Law2, M.E. Shenton2 & R.W. McCarley2
Saturday Abstracts
increasedvariabilityin EEG activity of schizophrenicpatients. In the present study we examined this issue of variability using MEG recordings of evoked auditory fields of patients with schizophrenia compared to controls. Using a 7 channel neuromagnetometer,we recorded MEG evoked fields to 200 unattended 30 msec IKHz tone pips from 35 positionson each hemisphere,in 33 subjects(16 patients with schizophrenia or schizoaffective disorder; 17 controls). The antenor and posterior extrema of the 100 msec latency component (M1OO)were selected from this ensemble. The standard deviation at each sample point across trirds was computed, and means were calculated in the 200 msec pre-stimulus and 250 msec post-stimulus regions,and averagedacross extremafor each subject.We foundthat, comparedto controls, there was indeed significantlygreater variance (F=7.93, p=.009, df= 1)in bothpre- and post- stimultrsregionsof the waveformin the patients with schizophrenia.Comparedto controls, however, the patients with schizophrenia exhibited a statistically significant decrease in variance (F=7.91, p=.01, df= 1) in the post-stimuluscomponentof the waveform.This suggests the esaentirdlyrandom“noise” (“choppiness”)of the backgroundwaveformin the schizophrenic subjects, possibly related to impaired inhibitory mechanisms, was diminished during the post-stimulus period. This may have been due to appropriate activation of the auditory cortex involved in processing the unattended stimuli, which therefore no longer contributedto a generalized increase in backgroundactivity. Supportedby USPHSMH 47476. Davis, P.A. Evaluationof the electroencephalogramof schizophrenic patients.Am. J. Psychiat.%:851-860,1940.
IPsychologyDepartment,Universityof Massachusetts,Boston ‘PsychiatryDepartment,HarvardMedicalSchooland Brockton
VAMC
We examined word recall in patients with schizophreniausing an experimentalparadigmgeneratedfromconnectionistmodelsof learning. Schizophrenicand comparisonsubjectsfmt studiedand then recalleda list of 32 wordsof equaldifficulty.Thewordsvaziedonthe basisof lmtb connectivity(associativestrength)and networksize (numberof associates), such that the list containedequal proportionsof four types of words:(1) high connectivity-smallnetworksize; (2) low connectivitysmrdlnetworksize;(3) highconnectivity-largenetworksize;and(4)low connectivity-largenetwork size. Schizophrenicpatients recaUedfewer words,and showeda particularlypronouncedeffectfor the connectivity of the to-be-rememberedwords.For patients,regardlessof the network size of a word,recall improvedsubstantiallyfor wordsof high cormectivity, and declined dramaticallyfor words of low connectivity.By contrast, comparisonsubjects showedthe expectedeffects, with best recall for words of high connectivity-smallnetworksize, followedby wordsof lowconnectivity-smallnetworksize,andthenby wordsof high connectivity-largenetworksize, and finallyby wordsof low comectivity-kirgenetwork size. Schizophreniamay be characterizedby faulty modulationof associativelinks within a lexiconthat is thoughtto be widelydistributedacrossfrontaland temporallobes.
401. VARIANCE IN THE AUDITORY EVOKED FIELD MAY REFLECT IMPAIRED INHIBITORY MECHANISMS IN SCHIZOPHRENIA J. Sheederl, P. Tealel, D. Rojasl & M. Reitel>2 *Universityof ColoradoHealthSciencesCenter,Denver,CO 80262; 2DenverVA MedicalCenter,Denver,CO 80220 Nearly 60 years ago, Pauline Davis described the EEG of patients with schizophreniaas “choppy” (DAVIS, 1940), a manifestationof
402. NEUROLEPTIC INDUCED DOPAMINE D2 RECEPTOR UP-REGULATION IN SCHIZOPHRENIA S. Silvestri, J. Schroeder, B. Bubeck & S. Demisch Universityof Heidelberg- Dept. of Psychiatry,Voss Str. 4, D-6900 Heidelberg,Germany D2 receptor up-regulation is a well established effect of typical neurolepticsin animal experimentswhich has been implicated in the developmentof tardive dyskinesia(TD). This study was aimed at the investigationof the relationshipbetween vulnerabilityfactors for TD and D2 receptor up-regulation in patients with schizophrenia. D2 receptorbindingof 15patients with schizophreniawas assessed using IZ31-~ZM SpECT fi the neuroleptic.naive state and 3 days titer withdrawalof a standardisedtreatment with benperidol 12-16mg/day for 25 days. Change in D2 receptor binding was defined by the differenceof the basal gangliato frontal cortex index before and after treatment withdrawal.Similarly,the change in the prolactin response to an intravenouschallengewith benperidol8 mg was determined.An elevation of D2receptor bindingwas measuredin 7 patients while an increased prolactin response was present in all patients. The increase of D2receptor binding was related to the severity of extrapyramidal symptoms (r = -.52; P< O.05) and to poor treatment response of affective symptomson the BPRS (r = -.58; p< O.05).The change of D2receptor binding in the right basal ganglia was more pronounced in male than in female patients (df = 1; F = 4.30; p= 0.06). The results suggest that neuroleptic induced elevation of D2 receptor binding in the basal ganglia and D2 receptor hypersensitivityin the tuberoinfundibuktrsystem display different patterns and that the elevationof D2receptor bindingin the basal gangliamay be useful as an early indicator of the vulnerabilityfor developingTD.
BIOLPSYCHIATRY 1998:43 :1S-133S
outcomesandcontinuedrehospitalimtions. Appropriatedosingis impmtant becausepatientswhoareunderdnsd or whoreceiveexcessivedosesmay fail to respond,especiallyif a drug has a therapeuticwindowfor an efficaciousdose.Noncompliance may also resultsecontkuyto side effect occurrence.Thissmdyexaminedtrendarelatedto risperidonedosingwithin the state systemand detaminedrecidivismrates for thosewhohad be=en discharged.All patientstxeatedwithinan inpatientstatepsychiatricfacility were includedin this computerizeddatabase.This datasetcontains1,057 patientrecordsand reflectsrisperidoneusagepatternssimilarto national data.Meanrisperidonedoseshavedeclinedsignificmtlyeachyearsinceits introductionin bothdischargedandhmpitalizedpatients.In 1996,patients (n=449)whoweredischargedreceivedsignificantlylowerdosesthanthose remaininghospitalized(4.3 vs. 5.6 mgMay,p
400. WORD RECALL IN SCHIZOPHRENIA: A CONNECTIONIST MODEL P.G. Nestorl’2, S.J. Akdagl>2,B.F. O’Donnell, M. Niznikiewicz2, S. Law2, M.E. Shenton2 & R.W. McCarley2
Saturday Abstracts
increasedvariabilityin EEG activity of schizophrenicpatients. In the present study we examined this issue of variability using MEG recordings of evoked auditory fields of patients with schizophrenia compared to controls. Using a 7 channel neuromagnetometer,we recorded MEG evoked fields to 200 unattended 30 msec IKHz tone pips from 35 positionson each hemisphere,in 33 subjects(16 patients with schizophrenia or schizoaffective disorder; 17 controls). The antenor and posterior extrema of the 100 msec latency component (M1OO)were selected from this ensemble. The standard deviation at each sample point across trirds was computed, and means were calculated in the 200 msec pre-stimulus and 250 msec post-stimulus regions,and averagedacross extremafor each subject.We foundthat, comparedto controls, there was indeed significantlygreater variance (F=7.93, p=.009, df= 1)in bothpre- and post- stimultrsregionsof the waveformin the patients with schizophrenia.Comparedto controls, however, the patients with schizophrenia exhibited a statistically significant decrease in variance (F=7.91, p=.01, df= 1) in the post-stimuluscomponentof the waveform.This suggests the esaentirdlyrandom“noise” (“choppiness”)of the backgroundwaveformin the schizophrenic subjects, possibly related to impaired inhibitory mechanisms, was diminished during the post-stimulus period. This may have been due to appropriate activation of the auditory cortex involved in processing the unattended stimuli, which therefore no longer contributedto a generalized increase in backgroundactivity. Supportedby USPHSMH 47476. Davis, P.A. Evaluationof the electroencephalogramof schizophrenic patients.Am. J. Psychiat.%:851-860,1940.
IPsychologyDepartment,Universityof Massachusetts,Boston ‘PsychiatryDepartment,HarvardMedicalSchooland Brockton
VAMC
We examined word recall in patients with schizophreniausing an experimentalparadigmgeneratedfromconnectionistmodelsof learning. Schizophrenicand comparisonsubjectsfmt studiedand then recalleda list of 32 wordsof equaldifficulty.Thewordsvaziedonthe basisof lmtb connectivity(associativestrength)and networksize (numberof associates), such that the list containedequal proportionsof four types of words:(1) high connectivity-smallnetworksize; (2) low connectivitysmrdlnetworksize;(3) highconnectivity-largenetworksize;and(4)low connectivity-largenetwork size. Schizophrenicpatients recaUedfewer words,and showeda particularlypronouncedeffectfor the connectivity of the to-be-rememberedwords.For patients,regardlessof the network size of a word,recall improvedsubstantiallyfor wordsof high cormectivity, and declined dramaticallyfor words of low connectivity.By contrast, comparisonsubjects showedthe expectedeffects, with best recall for words of high connectivity-smallnetworksize, followedby wordsof lowconnectivity-smallnetworksize,andthenby wordsof high connectivity-largenetworksize, and finallyby wordsof low comectivity-kirgenetwork size. Schizophreniamay be characterizedby faulty modulationof associativelinks within a lexiconthat is thoughtto be widelydistributedacrossfrontaland temporallobes.
401. VARIANCE IN THE AUDITORY EVOKED FIELD MAY REFLECT IMPAIRED INHIBITORY MECHANISMS IN SCHIZOPHRENIA J. Sheederl, P. Tealel, D. Rojasl & M. Reitel>2 *Universityof ColoradoHealthSciencesCenter,Denver,CO 80262; 2DenverVA MedicalCenter,Denver,CO 80220 Nearly 60 years ago, Pauline Davis described the EEG of patients with schizophreniaas “choppy” (DAVIS, 1940), a manifestationof
402. NEUROLEPTIC INDUCED DOPAMINE D2 RECEPTOR UP-REGULATION IN SCHIZOPHRENIA S. Silvestri, J. Schroeder, B. Bubeck & S. Demisch Universityof Heidelberg- Dept. of Psychiatry,Voss Str. 4, D-6900 Heidelberg,Germany D2 receptor up-regulation is a well established effect of typical neurolepticsin animal experimentswhich has been implicated in the developmentof tardive dyskinesia(TD). This study was aimed at the investigationof the relationshipbetween vulnerabilityfactors for TD and D2 receptor up-regulation in patients with schizophrenia. D2 receptorbindingof 15patients with schizophreniawas assessed using IZ31-~ZM SpECT fi the neuroleptic.naive state and 3 days titer withdrawalof a standardisedtreatment with benperidol 12-16mg/day for 25 days. Change in D2 receptor binding was defined by the differenceof the basal gangliato frontal cortex index before and after treatment withdrawal.Similarly,the change in the prolactin response to an intravenouschallengewith benperidol8 mg was determined.An elevation of D2receptor bindingwas measuredin 7 patients while an increased prolactin response was present in all patients. The increase of D2receptor binding was related to the severity of extrapyramidal symptoms (r = -.52; P< O.05) and to poor treatment response of affective symptomson the BPRS (r = -.58; p< O.05).The change of D2receptor binding in the right basal ganglia was more pronounced in male than in female patients (df = 1; F = 4.30; p= 0.06). The results suggest that neuroleptic induced elevation of D2 receptor binding in the basal ganglia and D2 receptor hypersensitivityin the tuberoinfundibuktrsystem display different patterns and that the elevationof D2receptor bindingin the basal gangliamay be useful as an early indicator of the vulnerabilityfor developingTD.