- Email: [email protected]
85. In vivo measurement of presynaptic dopamine innervation in schizophrenia
26S
BIOLPSYCHIATRY 1998;43:L%133S
volumeloss. In addition,it is unclear how alterationsin hippocampal volume,if present, affect neumcognitivefunctioningin schizophrenia. Therefore,the objective of this study is to: 1) determineif there is hippocampalvolume loss in schizophreniautilizing quantitativeMRI measures,and 2) determinewhetherdeficitsin neurocognitivefunctioning are related to alterationsin hippocampalvolumein schizophrenia. Sixteenmedicated,schizophrenicpatientsand 14normalcontrolsubjects underwent both MRI and a neuropsychologicalbattery. MRI was performedusing a SiemensMagnetomVisionsystemat the SFVAMC Magnetic ResonanceUnit. The schizophrenicpatients met DSM-IV criteria for schizophrenia. MRI imaging sequences included: T1 weighted scout localizer scans; 2) oblique axial DSE scans agulated parallelto the opticnerve(TWTEltTE2=3CtO0/20/80 ms, 1.0x 1.4mmz resolution,3mmthick slices);and 3) an MP RAGEacquisition(TfUIW TE = 10/250/4ms, flip angle 15degrees,1.0x 1.0mmzresolution,1.4 mm thick slices). Quantitativehippocampalvohmtingwas performed usingin-housesoftwareby a singleoperatorto yieldanterior,posterior, and total volumes for the right and left hippocampiin all subjects. Repeated measures ANOVA revealed that compared to the control group,the patientswith schizophreniademonstratedsignificantlylower anteriorhippocampalvolumesin the schizophrenicpatientsbilaterally.In addition,a significantliteralizedasymmetry(Right>Ldt) wasnotedfor the anteriorand total hippocampalvolumesin both the schizophrenics and controls.Regressionanalysisof the hippocamprdvolumemeasures with specificcomponentsof the neuropsychologicalbatteryrevealeda significant associationof left anterior hippocampalvolume loss and impairedperformanceon the WisconsinCard SortTest (WCS~. These results suggesta relationshipbetweenleft anteriorhippocampalvolume loss and a specific measure of frontal lobe executivefunctioningand furthersupporta pathologicprocesslinkingthe hippocampusandfrontal lobe in schizophrenia.
84. MULTI-SLICE IH MAGNETIC RESONANCE SPECTROSCOPIC IMAGING IN SCHIZOPHRENIA C. Johnsonl, R.F. Deickenl’2’3,N. Schuffl’4 & M. Weiner1>4’5 IMagneticResonanceUnit and 2PsychiatryService,San Francisco Dept.of VeteransAffairsMedicalCenter(.SFVAMC),and the Departmentsof 3Psychiatry,4Radiology,and ‘Medicine,Universityof California,San Francisco N-acetylaspartate(NAA) is a neurortahxonal marker present entirely withinneuronsand axonsbut not maturegliat cells. Multi-sliceproton (’H) magneticresonancespectroscopicimaging(MRSI)allowsmeasurement of NAAin manydifferentbrain regionssimultaneously.Utilizing MRSIpermitsthe simultaneousassessmentof neuronalloss or dysfunction in gray matter regionsas well as the assessmentof axonalloss or dysfunctionin whitemattcrregions.Sucha techniqueis extremelyuseful for studying schizophreniawhere the neuropathologyappears to be distributedthroughoutmultipleneuroanatomically linkedregions.llrerefore, the objectiveof this studywas to obtainmultipleregionalassessments of NAA using multi-slice IH MRSI. Seven medicated,schizophrenicpatientsand 6 normalcontrolsubjectshaveundergoneMRIand IH MRSIusing a SiemensMagnetomVisionMRUMRSsystemat the SFVAMCMagneticResonanceUnit. The schizophrenicpatients met DSM-IVcriteriafor schizophrenia.MRIimagingsequencesincludedT1 weightedscout views along with coronalMP RAGEand axial double spin-echoimages.Multislice‘H MRSIusing a three slice methodwas performedusingthe followingacquisitionparameters:TWI’E= 1960/ 135ms,36 phase-encodingsteps in each directionwith circulark-space sampling,280x 280mmzFOVproviding,8 x 8 mmzin planeresolution. Usingspectroscopicimagingdisplaysoftware,individualMRSIvoxels
Thursday Abstracts
(1.5 ml) were then selectedin the frontalgray matter and white matter regionsbilaterallyusingthe higherresolutionco-registeredMR images. IH spectra from these voxels were fit by an automatedcurve fitting softwareprogramdevelopedin our laboratory.Concentrationestimates of NAA,choline,andcreatinewereobtainedbycorrectingpeakintegrals by the transmitter reference smpli@de for each subject. Repeated measures ANOVArevealed that comparedto the control group, the patientswith schizophreniademonstrateddecreasedNAAin the frontal cortex, frontal white matter, anterior cingolate region, and thalamus. These results suggest that there is evidence for neuronaland axonal dysfunctionor lossin multipleneuroanatomicallylinkedbrainregionsin schizophrenia.
85. IN VIVO MEASUREMENT OF PRESYNAPTIC DOPAMINE INNERVATION IN
SCHIZOPHRENIA
S.F. Taylorl, R. Tandonl, J.-K. Zubietal’2, P. Huguelet2 & K.A. Frey2$3 ‘Universi~of MichiganDepartmentof Psychiatry,AnnArbor,Ml 48109-0116;‘MentalHerdthResearchInstitute,Ann Arbor,MI; 3Universityof MichiganDepartmentof InternalMedicine,Divisionof NuclearMedicine Recentworkhas shownthatschizophrenicpatientsexhibitgreaterrelease of dopamineduringamphetaminechallenge,a tindingwhichmayreflect either an alteredregulationof dopanrinerelease or a higherdensityof dopaminergicterminalsin the striatmn.Althoughpost-mortemdata does not showgreater terminaldensityin schizophrenia,age-relateddecline mayobscurea phenomenonpresentat the onsetof the illness.To test the hypothesisof altered pre-synapticdopaminevesicles in schizophrenia, weperformeda positronemissiontomographicstudyusing[C-1l]alphadihydrotetmbcnazine (DTBZ),whichbindsto the vesicularmonoamine transporter,type2 (VMAT2).We predictedthat DTBZbindingwouldbe greater in patients in the early phases of illness and reduced with chronicityof illness, relativeto healthycontrols.Patients (9 SZ, mean age = 38 * 11.2;11CTRL,meanage = 37.2 k 11.2)underwentPET imagingof [C-11]DTBZbindingduringequilibriuminfusionof tracer. Bindingwas estimatedfromthe tissue-to-plasmavolumeof distribution (DV).preliminaryanalysisof VMAT2in the putarnen,estimatedfrom DV relativeto occipitalcortex,showedthe expectedage-relateddecline in VMAT2,with a trend towardsmore rapid decline and higherinitial terminaldensityin the schizophrenicpatients.Thisnew applicationof in vivo measurementof prc-synapticdopamineimervation provides an importanttool for understandingabnormaldopaminergicfunction in schizophrenia.
86. RETROSPLENIAL CORTEX INVOLVEMENT IN PROCESSING THE EMOTIONAL MEANING OF STIMULI R.J. Maddoek, M.H. Buonocore & A.S. Garrett Departmentsof Psychiatryand Radiology,Universityof California, Davis,Schoolof Medicine,Sacramento,CA 95817 Unlike the amygdala,orbital, insular, and anterior cingulatc cortices, whichare widelyrecognizedas havingmajorroles in humanemotion, the retrosplenialcortexis generallybelievedto have no involvementin
BIOLPSYCHIATRY 1998;43:L%133S
volumeloss. In addition,it is unclear how alterationsin hippocampal volume,if present, affect neumcognitivefunctioningin schizophrenia. Therefore,the objective of this study is to: 1) determineif there is hippocampalvolume loss in schizophreniautilizing quantitativeMRI measures,and 2) determinewhetherdeficitsin neurocognitivefunctioning are related to alterationsin hippocampalvolumein schizophrenia. Sixteenmedicated,schizophrenicpatientsand 14normalcontrolsubjects underwent both MRI and a neuropsychologicalbattery. MRI was performedusing a SiemensMagnetomVisionsystemat the SFVAMC Magnetic ResonanceUnit. The schizophrenicpatients met DSM-IV criteria for schizophrenia. MRI imaging sequences included: T1 weighted scout localizer scans; 2) oblique axial DSE scans agulated parallelto the opticnerve(TWTEltTE2=3CtO0/20/80 ms, 1.0x 1.4mmz resolution,3mmthick slices);and 3) an MP RAGEacquisition(TfUIW TE = 10/250/4ms, flip angle 15degrees,1.0x 1.0mmzresolution,1.4 mm thick slices). Quantitativehippocampalvohmtingwas performed usingin-housesoftwareby a singleoperatorto yieldanterior,posterior, and total volumes for the right and left hippocampiin all subjects. Repeated measures ANOVA revealed that compared to the control group,the patientswith schizophreniademonstratedsignificantlylower anteriorhippocampalvolumesin the schizophrenicpatientsbilaterally.In addition,a significantliteralizedasymmetry(Right>Ldt) wasnotedfor the anteriorand total hippocampalvolumesin both the schizophrenics and controls.Regressionanalysisof the hippocamprdvolumemeasures with specificcomponentsof the neuropsychologicalbatteryrevealeda significant associationof left anterior hippocampalvolume loss and impairedperformanceon the WisconsinCard SortTest (WCS~. These results suggesta relationshipbetweenleft anteriorhippocampalvolume loss and a specific measure of frontal lobe executivefunctioningand furthersupporta pathologicprocesslinkingthe hippocampusandfrontal lobe in schizophrenia.
84. MULTI-SLICE IH MAGNETIC RESONANCE SPECTROSCOPIC IMAGING IN SCHIZOPHRENIA C. Johnsonl, R.F. Deickenl’2’3,N. Schuffl’4 & M. Weiner1>4’5 IMagneticResonanceUnit and 2PsychiatryService,San Francisco Dept.of VeteransAffairsMedicalCenter(.SFVAMC),and the Departmentsof 3Psychiatry,4Radiology,and ‘Medicine,Universityof California,San Francisco N-acetylaspartate(NAA) is a neurortahxonal marker present entirely withinneuronsand axonsbut not maturegliat cells. Multi-sliceproton (’H) magneticresonancespectroscopicimaging(MRSI)allowsmeasurement of NAAin manydifferentbrain regionssimultaneously.Utilizing MRSIpermitsthe simultaneousassessmentof neuronalloss or dysfunction in gray matter regionsas well as the assessmentof axonalloss or dysfunctionin whitemattcrregions.Sucha techniqueis extremelyuseful for studying schizophreniawhere the neuropathologyappears to be distributedthroughoutmultipleneuroanatomically linkedregions.llrerefore, the objectiveof this studywas to obtainmultipleregionalassessments of NAA using multi-slice IH MRSI. Seven medicated,schizophrenicpatientsand 6 normalcontrolsubjectshaveundergoneMRIand IH MRSIusing a SiemensMagnetomVisionMRUMRSsystemat the SFVAMCMagneticResonanceUnit. The schizophrenicpatients met DSM-IVcriteriafor schizophrenia.MRIimagingsequencesincludedT1 weightedscout views along with coronalMP RAGEand axial double spin-echoimages.Multislice‘H MRSIusing a three slice methodwas performedusingthe followingacquisitionparameters:TWI’E= 1960/ 135ms,36 phase-encodingsteps in each directionwith circulark-space sampling,280x 280mmzFOVproviding,8 x 8 mmzin planeresolution. Usingspectroscopicimagingdisplaysoftware,individualMRSIvoxels
Thursday Abstracts
(1.5 ml) were then selectedin the frontalgray matter and white matter regionsbilaterallyusingthe higherresolutionco-registeredMR images. IH spectra from these voxels were fit by an automatedcurve fitting softwareprogramdevelopedin our laboratory.Concentrationestimates of NAA,choline,andcreatinewereobtainedbycorrectingpeakintegrals by the transmitter reference smpli@de for each subject. Repeated measures ANOVArevealed that comparedto the control group, the patientswith schizophreniademonstrateddecreasedNAAin the frontal cortex, frontal white matter, anterior cingolate region, and thalamus. These results suggest that there is evidence for neuronaland axonal dysfunctionor lossin multipleneuroanatomicallylinkedbrainregionsin schizophrenia.
85. IN VIVO MEASUREMENT OF PRESYNAPTIC DOPAMINE INNERVATION IN
SCHIZOPHRENIA
S.F. Taylorl, R. Tandonl, J.-K. Zubietal’2, P. Huguelet2 & K.A. Frey2$3 ‘Universi~of MichiganDepartmentof Psychiatry,AnnArbor,Ml 48109-0116;‘MentalHerdthResearchInstitute,Ann Arbor,MI; 3Universityof MichiganDepartmentof InternalMedicine,Divisionof NuclearMedicine Recentworkhas shownthatschizophrenicpatientsexhibitgreaterrelease of dopamineduringamphetaminechallenge,a tindingwhichmayreflect either an alteredregulationof dopanrinerelease or a higherdensityof dopaminergicterminalsin the striatmn.Althoughpost-mortemdata does not showgreater terminaldensityin schizophrenia,age-relateddecline mayobscurea phenomenonpresentat the onsetof the illness.To test the hypothesisof altered pre-synapticdopaminevesicles in schizophrenia, weperformeda positronemissiontomographicstudyusing[C-1l]alphadihydrotetmbcnazine (DTBZ),whichbindsto the vesicularmonoamine transporter,type2 (VMAT2).We predictedthat DTBZbindingwouldbe greater in patients in the early phases of illness and reduced with chronicityof illness, relativeto healthycontrols.Patients (9 SZ, mean age = 38 * 11.2;11CTRL,meanage = 37.2 k 11.2)underwentPET imagingof [C-11]DTBZbindingduringequilibriuminfusionof tracer. Bindingwas estimatedfromthe tissue-to-plasmavolumeof distribution (DV).preliminaryanalysisof VMAT2in the putarnen,estimatedfrom DV relativeto occipitalcortex,showedthe expectedage-relateddecline in VMAT2,with a trend towardsmore rapid decline and higherinitial terminaldensityin the schizophrenicpatients.Thisnew applicationof in vivo measurementof prc-synapticdopamineimervation provides an importanttool for understandingabnormaldopaminergicfunction in schizophrenia.
86. RETROSPLENIAL CORTEX INVOLVEMENT IN PROCESSING THE EMOTIONAL MEANING OF STIMULI R.J. Maddoek, M.H. Buonocore & A.S. Garrett Departmentsof Psychiatryand Radiology,Universityof California, Davis,Schoolof Medicine,Sacramento,CA 95817 Unlike the amygdala,orbital, insular, and anterior cingulatc cortices, whichare widelyrecognizedas havingmajorroles in humanemotion, the retrosplenialcortexis generallybelievedto have no involvementin