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279. The hillside rapp clinic: intervention during the schizophrenia prodrome
84S
BIOLPSYCHL4TRY 1998;43:1S-133S
cognitive impairmentin healthy volunteersthat resembles aspects of schizophrenia.This similarity has been viewed as evidence for the involvement of the NMDA receptor is schizophrenia. We utilized subanesthetic doses of the NMDA antagonist, ketamine, to induce formal thoughtdisorder in healthy volunteers.Thoughtdisorder was assessed with the Scale of the Assessmentof Thought,Language,and Communication(TLC). Formal thought disorder in schizophrenic patients was similarly assessed with the TLC. We analyzed both groups of TLC ratings utilizing factors, as well as individual items and comparedthe two. Total TLC scores did not differ significantly between groups. Similarly, scores on the unidimensional seventy factor did not significantlydiffer; the positiveandnegativefactors did not significantlydiffer; and the verbal productionand disconnection factors failed to significantly differ. Of individual TLC items, only perseveration differed significantly between the two groups; with Bonferroni correction, no items differed significantly. Among the schizophrenicpatients, highest item scores were in povertyof speech, circumstantiality, loss of goal and poverty of content. In healthy volunteers receiving ketamine, highest scores were in the items for poverty of speech, circumstantiality,loss of goal and perseveration. These data suggestthat ketamine-inducedthoughtdisorderin healthy volunteersresembles schizophrenicthoughtdisorder.
279. THE HILLSIDE RAPP CLINIC: INTERVENTION DURING THE SCHIZOPHRENIA PRODROME B. Comblatt, M. Obuchowski, R. S. Goldman, A. Bergman, C. Smith, C. Baruch-Feldrnan & J. Becker Departmentof PsychiatryResearch,HillsideHospital,Glen Oaks,NY 11004 The schizophreniapmdmmeis consideredto be the periodfromthe tirst noticeablechangein behaviorto the emergenceof psychoticsymptoms. Interestin this stageof schizophreniahas recentlyincreaseddramatically with the recognitionthat the eartier the treatmentbeginsatler onset of psychosis, the better the early prognosis. It therefore follows that interventionbeginningbefore psychosis takes hold, i.e., during the pmdmmalperiod,may be the most effectivetreatmentpossible.
Saturday Abstracts
280. THE FIVE-FACTOR PERSONALITY MODEL IN SCHIZOPHRENIA R.J. Gurrera, N. Akhtar, S. Akdag, B. O’Donnell, P. Nestor & R.W. McCarley HarvardMedicalSchool,BostonMA 02115and Brockton-West RoxbutyDVAMC,BmcktonMA 02401 We examinedpersonalitydifferencesamongnormaland schizophrenic subjects using the five-factormodel of personality.NEO Five-Factor Inventory(FormS; Costa & McCrae, 1991)scale scores were used to assess five persomditydomains: neuroticism (N), extroversion (E), openness(0), agreeableness(A), and conscientiousness(C). Patients were medicatedand met DSM-IVcriteriafor chronicschizophrenia.All subjectswere male. Schizophrenics(n=25) differedsignificantlyfrom normrds(n=46) (F=3.36, df=65, p=.009) by one-way MANOVA. Schizophrenicmeanscoresweresignificantlyhigheron N (22.6vs 15.5; F=15.93, df= (1,69),pc.0005) and significantlylower on C (30.3 vs 34.1; F=4.91, df=(l,69), p=.03) and E (25.6 VS 29.0; F=4.35, df=(l,69), p=.041). Schizophrenicsalso showeda trend towardlower meanscoreson O (26.7vs 29.3;F=2.91, df= (1,69),p=.092). Basedon their reviewand meta-analysisof non-NEOdata Berenbaumand Fujita (1994)concludedthat schizophrenicsare moreintroverted,neuroticand peculiarthan normalsubjects.Comparedto normativedata, non-acute schizophrenicsscore higher on NEO-Nand lower on NEO-E and -A dimensions(Bagbyet al, 1997).In contrastto Bagbyet rd,we foundthat schizophrenicsscoreloweron C (i.e., are less purposeful,strong-willed, determined,scmpuious,punctual,reliable)and possiblyO (i.e., are less imaginative,aestheticallysensitive, intellectuallycurious, attentive to imer feelings), but do not differ from normals on A (interpersonal tendenciesof altruism,sympathy,cooperativeness,trust). Thus, schizophrenicsubjectsin oursampledifferedmoredistinctlyfromnormalsthan has beenshownpreviouslyusingnormativedata.To ourknowledge,this is the f~st time that the NEOFFI has been used to measurepersonality traits in schizophrenicpatientsand normalcontrols. REFERENCES:Bagbyet al (1997) Fkychiat~ Res, 70:83-94;Berenbaom& Fujita (1994).fAbnmm Psychol, 103:148-158.
281. TIME HOSPITALIZED PREDICTS RATE OF CORTICAL GRAY MATTER LOSS IN SCHIZOPHRENIA D.H. Mathalonl, E.V. Sullivanl, K.O. Lim192& A. Pfefferbauml’3
The RAPPclinic,whichis part of the Divisionof High-RiskStudiesat HillsideHospital,is a veryrecentlyinitiatedprogramconcernedwithall aspectsof the prodromalphaseof schizophrenia.Theprogramintegrates research and a varie~ of treatment strategies, and targets pmdromal patientsbetweenthe ages of 13and 25.
IDept.of Psychiatryand BehaviorrdSciences,StanfordUniversity Schoolof Medicine,‘VA Palo Alto HealthCare System,Stanford,CA 94305,and Centerfor HealthSciences,3SFUInternational,333 RavenswocdAvenue,MenloPark,CA 94025
In this report, we will introduce the RAPP clinic, describe the underlyingtheoreticalrationaleand outlinethe essentialaspects of the early interventionand research componentsof the program.Preliminary findingscomparingthe RAPPpatients, who are consideredto be at clinical risk for schizophrenia,with age-matchedsubjectsat genetic risk will be presented. Findingsfrom the Hillside Study of Risk and Early Detection in Schizophreniahave shownthat at-risk siblings of schizophrenic patients (ages 13-25) display substantial deficits in attention and short-termmemoryand are characterizedby features in AXIS 11 paranoid and schizotypal personality disorders. In this presentation, particular focus will be directed to the extent to which the RAPPclinic patients display neurocognitivedeficits and AXIS11 features that are consistent with those characterizing the genetically at-risk siblings of schizophrenia.
If psychosisper se is neurotoxic,then more severelyill schizophrenics should show greater brain volume loss over time. Previously, we examinedrates of MRI volumechanges(cc/year)for sulcaland ventricular CSFandcorticalgraymatterover an averageintervalof four years in 24 schizophrenicmen (age=39.4 *6.4 years, interval=3.6 k2.2 years).Resultsshoweda difiirsebrain volumedeclinein schizophrenia, relative to controls. Positive symptomspredicted a faster decline in frontal, temporal, and parietal cortical gray matter, while negative symptomspredicteda fasterdeclinein prefrontalgraymatterandgreater expansionof the third ventricle.In this report (23 schizophrenics,one outlier excluded),the proportionof days hospitalizedbetween MRI scans,reflectingclinicalseverityduringthe interscarrinterval,was used to predictthe rate of volumechangein corticalsulci and gray matterin six regions of interest, as well as ventricular CSF. Patients were
BIOLPSYCHL4TRY 1998;43:1S-133S
cognitive impairmentin healthy volunteersthat resembles aspects of schizophrenia.This similarity has been viewed as evidence for the involvement of the NMDA receptor is schizophrenia. We utilized subanesthetic doses of the NMDA antagonist, ketamine, to induce formal thoughtdisorder in healthy volunteers.Thoughtdisorder was assessed with the Scale of the Assessmentof Thought,Language,and Communication(TLC). Formal thought disorder in schizophrenic patients was similarly assessed with the TLC. We analyzed both groups of TLC ratings utilizing factors, as well as individual items and comparedthe two. Total TLC scores did not differ significantly between groups. Similarly, scores on the unidimensional seventy factor did not significantlydiffer; the positiveandnegativefactors did not significantlydiffer; and the verbal productionand disconnection factors failed to significantly differ. Of individual TLC items, only perseveration differed significantly between the two groups; with Bonferroni correction, no items differed significantly. Among the schizophrenicpatients, highest item scores were in povertyof speech, circumstantiality, loss of goal and poverty of content. In healthy volunteers receiving ketamine, highest scores were in the items for poverty of speech, circumstantiality,loss of goal and perseveration. These data suggestthat ketamine-inducedthoughtdisorderin healthy volunteersresembles schizophrenicthoughtdisorder.
279. THE HILLSIDE RAPP CLINIC: INTERVENTION DURING THE SCHIZOPHRENIA PRODROME B. Comblatt, M. Obuchowski, R. S. Goldman, A. Bergman, C. Smith, C. Baruch-Feldrnan & J. Becker Departmentof PsychiatryResearch,HillsideHospital,Glen Oaks,NY 11004 The schizophreniapmdmmeis consideredto be the periodfromthe tirst noticeablechangein behaviorto the emergenceof psychoticsymptoms. Interestin this stageof schizophreniahas recentlyincreaseddramatically with the recognitionthat the eartier the treatmentbeginsatler onset of psychosis, the better the early prognosis. It therefore follows that interventionbeginningbefore psychosis takes hold, i.e., during the pmdmmalperiod,may be the most effectivetreatmentpossible.
Saturday Abstracts
280. THE FIVE-FACTOR PERSONALITY MODEL IN SCHIZOPHRENIA R.J. Gurrera, N. Akhtar, S. Akdag, B. O’Donnell, P. Nestor & R.W. McCarley HarvardMedicalSchool,BostonMA 02115and Brockton-West RoxbutyDVAMC,BmcktonMA 02401 We examinedpersonalitydifferencesamongnormaland schizophrenic subjects using the five-factormodel of personality.NEO Five-Factor Inventory(FormS; Costa & McCrae, 1991)scale scores were used to assess five persomditydomains: neuroticism (N), extroversion (E), openness(0), agreeableness(A), and conscientiousness(C). Patients were medicatedand met DSM-IVcriteriafor chronicschizophrenia.All subjectswere male. Schizophrenics(n=25) differedsignificantlyfrom normrds(n=46) (F=3.36, df=65, p=.009) by one-way MANOVA. Schizophrenicmeanscoresweresignificantlyhigheron N (22.6vs 15.5; F=15.93, df= (1,69),pc.0005) and significantlylower on C (30.3 vs 34.1; F=4.91, df=(l,69), p=.03) and E (25.6 VS 29.0; F=4.35, df=(l,69), p=.041). Schizophrenicsalso showeda trend towardlower meanscoreson O (26.7vs 29.3;F=2.91, df= (1,69),p=.092). Basedon their reviewand meta-analysisof non-NEOdata Berenbaumand Fujita (1994)concludedthat schizophrenicsare moreintroverted,neuroticand peculiarthan normalsubjects.Comparedto normativedata, non-acute schizophrenicsscore higher on NEO-Nand lower on NEO-E and -A dimensions(Bagbyet al, 1997).In contrastto Bagbyet rd,we foundthat schizophrenicsscoreloweron C (i.e., are less purposeful,strong-willed, determined,scmpuious,punctual,reliable)and possiblyO (i.e., are less imaginative,aestheticallysensitive, intellectuallycurious, attentive to imer feelings), but do not differ from normals on A (interpersonal tendenciesof altruism,sympathy,cooperativeness,trust). Thus, schizophrenicsubjectsin oursampledifferedmoredistinctlyfromnormalsthan has beenshownpreviouslyusingnormativedata.To ourknowledge,this is the f~st time that the NEOFFI has been used to measurepersonality traits in schizophrenicpatientsand normalcontrols. REFERENCES:Bagbyet al (1997) Fkychiat~ Res, 70:83-94;Berenbaom& Fujita (1994).fAbnmm Psychol, 103:148-158.
281. TIME HOSPITALIZED PREDICTS RATE OF CORTICAL GRAY MATTER LOSS IN SCHIZOPHRENIA D.H. Mathalonl, E.V. Sullivanl, K.O. Lim192& A. Pfefferbauml’3
The RAPPclinic,whichis part of the Divisionof High-RiskStudiesat HillsideHospital,is a veryrecentlyinitiatedprogramconcernedwithall aspectsof the prodromalphaseof schizophrenia.Theprogramintegrates research and a varie~ of treatment strategies, and targets pmdromal patientsbetweenthe ages of 13and 25.
IDept.of Psychiatryand BehaviorrdSciences,StanfordUniversity Schoolof Medicine,‘VA Palo Alto HealthCare System,Stanford,CA 94305,and Centerfor HealthSciences,3SFUInternational,333 RavenswocdAvenue,MenloPark,CA 94025
In this report, we will introduce the RAPP clinic, describe the underlyingtheoreticalrationaleand outlinethe essentialaspects of the early interventionand research componentsof the program.Preliminary findingscomparingthe RAPPpatients, who are consideredto be at clinical risk for schizophrenia,with age-matchedsubjectsat genetic risk will be presented. Findingsfrom the Hillside Study of Risk and Early Detection in Schizophreniahave shownthat at-risk siblings of schizophrenic patients (ages 13-25) display substantial deficits in attention and short-termmemoryand are characterizedby features in AXIS 11 paranoid and schizotypal personality disorders. In this presentation, particular focus will be directed to the extent to which the RAPPclinic patients display neurocognitivedeficits and AXIS11 features that are consistent with those characterizing the genetically at-risk siblings of schizophrenia.
If psychosisper se is neurotoxic,then more severelyill schizophrenics should show greater brain volume loss over time. Previously, we examinedrates of MRI volumechanges(cc/year)for sulcaland ventricular CSFandcorticalgraymatterover an averageintervalof four years in 24 schizophrenicmen (age=39.4 *6.4 years, interval=3.6 k2.2 years).Resultsshoweda difiirsebrain volumedeclinein schizophrenia, relative to controls. Positive symptomspredicted a faster decline in frontal, temporal, and parietal cortical gray matter, while negative symptomspredicteda fasterdeclinein prefrontalgraymatterandgreater expansionof the third ventricle.In this report (23 schizophrenics,one outlier excluded),the proportionof days hospitalizedbetween MRI scans,reflectingclinicalseverityduringthe interscarrinterval,was used to predictthe rate of volumechangein corticalsulci and gray matterin six regions of interest, as well as ventricular CSF. Patients were