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psychosis
165
m
SYSTEMS FuNcrIoN
IN SCHIzoFHRENIA/PIs
M.D.: Charles L. JWwden, M.D.: dames w. Maas, M.D.*: Salvador A. m, Ennias Seleshi, M.D.: Alexander L. Miller, M.D. DepartmentofRychiatry,'LheUniversityofTews~~Sciem=eCenterat san Antonio, 770-3 Floyd Curl Drive, San Antonio, TX 78284-7792 preClinicdlstudieshaveledtothesuggestionthatacutepsychotic disoIde.rsaKeassociatedwithhypsractivity incentral nemous sY=t= PJS) neuratransnittersystms. Theneuratransmittersystmsthathavereceived particularattentiolarethe(Nsdopamine(DA)ardthe~ep~~(~) syste~.Clinicalstudiesofthesesystemshavebee.nhmkmd because it is difficult to easily and repeatedlyobtain biological saqles framh~subjectswhichreflectcNSneuratransnitte~aactivity. Giventhispmblem, wehavekiorkkitowards the develapnent ofmethodsby whi& measures in plasm or urine of hcmvanillic acid (HVA), the main metabolite of brain DA, and 3-methoxy-4-hydmxyphenylglyml (MHFG),the majormetaboliteofbrainNE, willrespectivelyprovide information regarding CNS dopmimqic and noradreneryicactivity. More specifically, ~haveprwiauslyreportedthatinpatientswfioarereceivingdebrisoquin sulfate, amomamim oxidaseinhibitorwhichdoesnotpenetratebrain, measuresofplasmaMHIGandHvAreflectneurotransnittersynthesisaIxI metabolisminbrainardthatthese measures have significantrelationship5 totheseverityofpsychosis. Wereporthemonmeasuxs of metabolites of DAandNE inplasm,urine, andcenbrospinal fluid (CSF) ofpatientswith acutepsychaticstatesandhealthynormdlcantrolsubjects. Wehavefouml thatwhile receivingdebrisoquin,butnotbefore, patientshave significantlyhigherlevels 0fHVAardMHPG inmostallbody fluids examimd andats.everaltimepoinlx. Wehypothesizethatacutepsychoticdisorders areassociatedwithhyperactivity in~~Snoradmmeqicneuratransmitter systemsandthatthe kxeasedlevelsoftheDAmetakolite, HVA, is seam%rytothis~ in brain NE system activity: i.e. psychatic/sckizoFhrenicjectshavean~NEreleasef~b~in systemswithaconsequentincrease i.nlevelsofHmand/orMHFG inurine, plasma and possibly CSF.
m
SYSTEMS FuNcrIoN
IN SCHIzoFHRENIA/PIs
M.D.: Charles L. JWwden, M.D.: dames w. Maas, M.D.*: Salvador A. m, Ennias Seleshi, M.D.: Alexander L. Miller, M.D. DepartmentofRychiatry,'LheUniversityofTews~~Sciem=eCenterat san Antonio, 770-3 Floyd Curl Drive, San Antonio, TX 78284-7792 preClinicdlstudieshaveledtothesuggestionthatacutepsychotic disoIde.rsaKeassociatedwithhypsractivity incentral nemous sY=t= PJS) neuratransnittersystms. Theneuratransmittersystmsthathavereceived particularattentiolarethe(Nsdopamine(DA)ardthe~ep~~(~) syste~.Clinicalstudiesofthesesystemshavebee.nhmkmd because it is difficult to easily and repeatedlyobtain biological saqles framh~subjectswhichreflectcNSneuratransnitte~aactivity. Giventhispmblem, wehavekiorkkitowards the develapnent ofmethodsby whi& measures in plasm or urine of hcmvanillic acid (HVA), the main metabolite of brain DA, and 3-methoxy-4-hydmxyphenylglyml (MHFG),the majormetaboliteofbrainNE, willrespectivelyprovide information regarding CNS dopmimqic and noradreneryicactivity. More specifically, ~haveprwiauslyreportedthatinpatientswfioarereceivingdebrisoquin sulfate, amomamim oxidaseinhibitorwhichdoesnotpenetratebrain, measuresofplasmaMHIGandHvAreflectneurotransnittersynthesisaIxI metabolisminbrainardthatthese measures have significantrelationship5 totheseverityofpsychosis. Wereporthemonmeasuxs of metabolites of DAandNE inplasm,urine, andcenbrospinal fluid (CSF) ofpatientswith acutepsychaticstatesandhealthynormdlcantrolsubjects. Wehavefouml thatwhile receivingdebrisoquin,butnotbefore, patientshave significantlyhigherlevels 0fHVAardMHPG inmostallbody fluids examimd andats.everaltimepoinlx. Wehypothesizethatacutepsychoticdisorders areassociatedwithhyperactivity in~~Snoradmmeqicneuratransmitter systemsandthatthe kxeasedlevelsoftheDAmetakolite, HVA, is seam%rytothis~ in brain NE system activity: i.e. psychatic/sckizoFhrenicjectshavean~NEreleasef~b~in systemswithaconsequentincrease i.nlevelsofHmand/orMHFG inurine, plasma and possibly CSF.