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88. Proton MRS in schizophrenia: Differences from controls and psychiatric symptom correlates
Thursday Abstracts
emotion.A clear demonstrationthat the retrospleniafcortexparticipates in emotionalprocessingwouldchallengecurrent views of the cortical regionsinvolvedin emotion.Surprisingly,mosttimctionalneoroimaging studiesof emotionallymeaningfulstimuliobservesignificantactivation in the retrosplenialcortex,but little significancehas beerrattributedto this. Our recent fMRIstudyof threat-relatedspokenwordsshowedthat retrosplenialcortexis more stronglyand consistentlyactivatedthan any otherregion,and may contributeto the effectsof emotionon memory. The currentstudytests the hypothesisthat retrosplenialcortexactivates duringprocessingof emotionallymeaningfulstimuliin general, that is, withoutrespectto valence(unpleasantvs. pleasant),modrdity(auditory vs. visual),or format(verbalvs. pictorial). Four subjectswere scannedwhile evaluatingalternating16”blocks of emotionallysalient and matched neutral spoken words. Emotionally salient words were either intensely unpleasantor intensely pleasant. Activationof retrosplenialcortex was observed with both intensely unpleasantand intenselypleasantwordsin 3 of 4 subjects.The lomtion of activationwith unpleasantand pleasantwords was identicafwithin subjects. Activation was stronger for pleasant words. One subjeet scannedwhile evaluatingvisuallypresentedpleasant words also activated retrosplenialcortex in the same location.Data from additional subjectsscarmedwhileevrduatingvisuallypresentedemotionallysalient wordsand pictureswill also be presented.These studieswill providea first test of the hypothesisthat the retrosplerrialcortexhas a role in the processingof affectivelymeaningfulstimuliwithoutrespectto valence, modalityor format.
87. PREFRONTAL CORTEX VOLUME IN CHRONIC SCHIZOPHRENIA: AN MRI REPLICATION STUDY. C.G. Wible, M.E. Shenton, R. Kikinis, F. Jolesz & R.W. McCarley HarvardMedicrdSchool,BrocktonVAMC,Brockton,MA 02401 Prefrontal cortical gray matter and white matter were measured in chronic schizophrenic(SZ) subjectsand matchedcontrols.This study wasdesignedas a replicationof a previousstudyof chronicSZin which prefrontal volume was not found to differ between SZ and control groups.However,the currentstudyexamineda muchhigherproportion of patientsshowingpredominantlynegativesymptomsthanthe previous study.Subjectswere 17right-handedmale SZ patientsand 17matched male controls.Gray matter was measuredusing 1.5 X .94 X .94 mm3 SPGRMRimagesthatwereacquiredusinga 1.5T system.Segmentation wasdoneusinga semi-automatedsegmentationteehniquein conjunction with manual editing. A three-factorrepeated measures ANOVAwas performedusingthe factorsgroup(SZandcontrol),tissue(grayor white matter) and side (right or left). The main finding of interest was a significant interaction of group, side, and tissue (F=8.04, df=l,32, P<.01). There were no significanteffects of groupor groupby tissue. T-tests showedreducedright whitemattervolumesin SZ subjects.Left and right prefrontalgray matter volumeswere also significantlynegativelycorrelatedwithtotalSANSscores(r.52;p<.05 for left graymatter andr.42;P<.05 for the right).SZ subjeets,but notcontrols,also showed a significantcorrelationbetweenrightprefrontalgraymattervolumeand right posterior amygdala-hippocampalcomplex volume (r=.73; p<.001). Theresultsconfm thoseof a previousstudyin ourlaboratory showing that prefrontal gray matter volume was not si@lcarrtly different between SZ and control subjects.High correlationsbetween temporaland prefrontalgraymatterregionswere also foundpreviously, but the correlationswere left-literalizedin SZ subjects.Thefindingof a right-laterdizcdreductionin whitemattervolumein SZ subjectsin this groupmay be relatedto the negativesymptomprofileof this group.
B1OLPSYCHIATRY 1998;43:1S-133S
27S
88. PROTON MRS IN SCHIZOPHRENIA: DIFFERENCES FROM CONTROLS AND PSYCHIATRIC SYMPTOM CORRELATES
J. Ventura, M.A. Thomas, B. Guze, A. Huda & D. Gutkind Universityof California,Los Angeles ProtonMR spectroscopystudies of patients with schizophreniareport reductionsof N-acetyl-aspartate(NAA)concentrationsin the prefrontal cortex and basal ganglia, but the findings have been inconsistent. Furthermore,the relationshipbetweenbrainneurochemistryand clinical symptomshas not beerrfolly investigated.Ten stable outpatientswith schizophreniawere compared to eleven normrdcontrols. Diagnostic screening and psychiatric symptomassessment was done by trained raters using the SCID-I and BPRS. A STEAMsequence (lWfE = 1500/20ms) witha 8 ml voxelsize was usedto examineratiosof NAA, Choline(Cho),myoinositol(orI),and Glutamateand Glutamine(Glx),to creating concentrationsin the medial frontal lobe and the nghtieft basal ganglia.NAA/Crratios were significantlylower in schizophrenia patients(Mean = 1.28)comparedto normals(Mean = 1.58,t = 2.34, p<.05). There were no other significantmetabolic ratio differencesin themedialfrontallobeor basalganglia.Forthe 10schizophreniapatients medialfrontrdNAA/Crwas significantlycorrelatedwith BPRSdepressive (r = .74, p=.012) and positive (r = .80, p=.005) symptoms. Negative symptomswere positivelycorrelated with rnI/Cr (r = .75, P=.olo). The abnormallylow concentrationof medial frontal NAA is consistentwiththeoriesof loss of neuronalintegrityin the frontallobes of schizophreniapatients.The correlationsof medialfrontalNAAwith depressiveand positivesymptomsis difficultto interpretand requires reification. However,the correlationswith medial frontal myoinositol suggestthat negativesymptomsmaybe associatedwitha breakdownof the neuronalintegrityof the cell.
89. A POTENTIAL CHOLINERGIC MECHANISM OF PROCAINE’S LIMBIC ACTIVATION B.E. Bensonl, R.E. Carson2, W. Sandova12, W.L. Linthicum2, T.A. Kimbrelll, D.O. Kieswette#, P. Herscovitch2, W.C. Eckelman2, U.D. McCarml, S.R.B. Weissl, R.M. Postl & T.A. Kette~ IBiologicalPsychiatryBranch,NIMH,NJ.H,Bethesda,MD, 20892, 2PETDepartment,NIH, Bethesda,MD, 20892,3StanfordUniversity Schoolof Medicine,Stanford,CA, 94305 In healthy volunteers,acute intravenousadministrationof the local anestheticprocaine results in transient robust emotionalaud seusory experiences,andincreasesin amygdalarand anteriorpsralimbiccerebraf bloodflow (CBF).Patientswith mcmddisordershave bluntedprocaineinducedCBFresponse,despitesimilarbehavioralresponses.Although, procaine is considered primarily a use-independentsodium charmel blocker,it exhibitshigheraffinityfor cholinergicmuscarinicM2 receptors. The anteriorparalimbicdistributionof the basal forebraincholinergic cell groupsand their immediateefferentsresemblesthe procairreinducedCBFactivationpattern.Tbus,we exploredwhethera muscarinic mechanismcouldcontributeto proeairre’seffeets. Weusedpositronemissiontomographyandtheradiotracer[18FJFP-TZfP, a ligandwiththehighestaftinityto cholinergicmuscarinicM2receptors,to m~~ -’s muse~c ~~ty. B*~e [18Fl~-m were cokctcdjustpnorto [18flFP-TZTPscansduringconstantpromineinfusion
emotion.A clear demonstrationthat the retrospleniafcortexparticipates in emotionalprocessingwouldchallengecurrent views of the cortical regionsinvolvedin emotion.Surprisingly,mosttimctionalneoroimaging studiesof emotionallymeaningfulstimuliobservesignificantactivation in the retrosplenialcortex,but little significancehas beerrattributedto this. Our recent fMRIstudyof threat-relatedspokenwordsshowedthat retrosplenialcortexis more stronglyand consistentlyactivatedthan any otherregion,and may contributeto the effectsof emotionon memory. The currentstudytests the hypothesisthat retrosplenialcortexactivates duringprocessingof emotionallymeaningfulstimuliin general, that is, withoutrespectto valence(unpleasantvs. pleasant),modrdity(auditory vs. visual),or format(verbalvs. pictorial). Four subjectswere scannedwhile evaluatingalternating16”blocks of emotionallysalient and matched neutral spoken words. Emotionally salient words were either intensely unpleasantor intensely pleasant. Activationof retrosplenialcortex was observed with both intensely unpleasantand intenselypleasantwordsin 3 of 4 subjects.The lomtion of activationwith unpleasantand pleasantwords was identicafwithin subjects. Activation was stronger for pleasant words. One subjeet scannedwhile evaluatingvisuallypresentedpleasant words also activated retrosplenialcortex in the same location.Data from additional subjectsscarmedwhileevrduatingvisuallypresentedemotionallysalient wordsand pictureswill also be presented.These studieswill providea first test of the hypothesisthat the retrosplerrialcortexhas a role in the processingof affectivelymeaningfulstimuliwithoutrespectto valence, modalityor format.
87. PREFRONTAL CORTEX VOLUME IN CHRONIC SCHIZOPHRENIA: AN MRI REPLICATION STUDY. C.G. Wible, M.E. Shenton, R. Kikinis, F. Jolesz & R.W. McCarley HarvardMedicrdSchool,BrocktonVAMC,Brockton,MA 02401 Prefrontal cortical gray matter and white matter were measured in chronic schizophrenic(SZ) subjectsand matchedcontrols.This study wasdesignedas a replicationof a previousstudyof chronicSZin which prefrontal volume was not found to differ between SZ and control groups.However,the currentstudyexamineda muchhigherproportion of patientsshowingpredominantlynegativesymptomsthanthe previous study.Subjectswere 17right-handedmale SZ patientsand 17matched male controls.Gray matter was measuredusing 1.5 X .94 X .94 mm3 SPGRMRimagesthatwereacquiredusinga 1.5T system.Segmentation wasdoneusinga semi-automatedsegmentationteehniquein conjunction with manual editing. A three-factorrepeated measures ANOVAwas performedusingthe factorsgroup(SZandcontrol),tissue(grayor white matter) and side (right or left). The main finding of interest was a significant interaction of group, side, and tissue (F=8.04, df=l,32, P<.01). There were no significanteffects of groupor groupby tissue. T-tests showedreducedright whitemattervolumesin SZ subjects.Left and right prefrontalgray matter volumeswere also significantlynegativelycorrelatedwithtotalSANSscores(r.52;p<.05 for left graymatter andr.42;P<.05 for the right).SZ subjeets,but notcontrols,also showed a significantcorrelationbetweenrightprefrontalgraymattervolumeand right posterior amygdala-hippocampalcomplex volume (r=.73; p<.001). Theresultsconfm thoseof a previousstudyin ourlaboratory showing that prefrontal gray matter volume was not si@lcarrtly different between SZ and control subjects.High correlationsbetween temporaland prefrontalgraymatterregionswere also foundpreviously, but the correlationswere left-literalizedin SZ subjects.Thefindingof a right-laterdizcdreductionin whitemattervolumein SZ subjectsin this groupmay be relatedto the negativesymptomprofileof this group.
B1OLPSYCHIATRY 1998;43:1S-133S
27S
88. PROTON MRS IN SCHIZOPHRENIA: DIFFERENCES FROM CONTROLS AND PSYCHIATRIC SYMPTOM CORRELATES
J. Ventura, M.A. Thomas, B. Guze, A. Huda & D. Gutkind Universityof California,Los Angeles ProtonMR spectroscopystudies of patients with schizophreniareport reductionsof N-acetyl-aspartate(NAA)concentrationsin the prefrontal cortex and basal ganglia, but the findings have been inconsistent. Furthermore,the relationshipbetweenbrainneurochemistryand clinical symptomshas not beerrfolly investigated.Ten stable outpatientswith schizophreniawere compared to eleven normrdcontrols. Diagnostic screening and psychiatric symptomassessment was done by trained raters using the SCID-I and BPRS. A STEAMsequence (lWfE = 1500/20ms) witha 8 ml voxelsize was usedto examineratiosof NAA, Choline(Cho),myoinositol(orI),and Glutamateand Glutamine(Glx),to creating concentrationsin the medial frontal lobe and the nghtieft basal ganglia.NAA/Crratios were significantlylower in schizophrenia patients(Mean = 1.28)comparedto normals(Mean = 1.58,t = 2.34, p<.05). There were no other significantmetabolic ratio differencesin themedialfrontallobeor basalganglia.Forthe 10schizophreniapatients medialfrontrdNAA/Crwas significantlycorrelatedwith BPRSdepressive (r = .74, p=.012) and positive (r = .80, p=.005) symptoms. Negative symptomswere positivelycorrelated with rnI/Cr (r = .75, P=.olo). The abnormallylow concentrationof medial frontal NAA is consistentwiththeoriesof loss of neuronalintegrityin the frontallobes of schizophreniapatients.The correlationsof medialfrontalNAAwith depressiveand positivesymptomsis difficultto interpretand requires reification. However,the correlationswith medial frontal myoinositol suggestthat negativesymptomsmaybe associatedwitha breakdownof the neuronalintegrityof the cell.
89. A POTENTIAL CHOLINERGIC MECHANISM OF PROCAINE’S LIMBIC ACTIVATION B.E. Bensonl, R.E. Carson2, W. Sandova12, W.L. Linthicum2, T.A. Kimbrelll, D.O. Kieswette#, P. Herscovitch2, W.C. Eckelman2, U.D. McCarml, S.R.B. Weissl, R.M. Postl & T.A. Kette~ IBiologicalPsychiatryBranch,NIMH,NJ.H,Bethesda,MD, 20892, 2PETDepartment,NIH, Bethesda,MD, 20892,3StanfordUniversity Schoolof Medicine,Stanford,CA, 94305 In healthy volunteers,acute intravenousadministrationof the local anestheticprocaine results in transient robust emotionalaud seusory experiences,andincreasesin amygdalarand anteriorpsralimbiccerebraf bloodflow (CBF).Patientswith mcmddisordershave bluntedprocaineinducedCBFresponse,despitesimilarbehavioralresponses.Although, procaine is considered primarily a use-independentsodium charmel blocker,it exhibitshigheraffinityfor cholinergicmuscarinicM2 receptors. The anteriorparalimbicdistributionof the basal forebraincholinergic cell groupsand their immediateefferentsresemblesthe procairreinducedCBFactivationpattern.Tbus,we exploredwhethera muscarinic mechanismcouldcontributeto proeairre’seffeets. Weusedpositronemissiontomographyandtheradiotracer[18FJFP-TZfP, a ligandwiththehighestaftinityto cholinergicmuscarinicM2receptors,to m~~ -’s muse~c ~~ty. B*~e [18Fl~-m were cokctcdjustpnorto [18flFP-TZTPscansduringconstantpromineinfusion