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250. The dopamine hypothesis of schizophrenia—alive, well and moving ahead
Saturday Abstracts
The Dopamine Hypothesis of SchizophreniaAlive, Well, and Moving Ahead Saturday,May 30, 12:15 PM-2:15 PM, Location Pier 7 Chairperson:Shitij Kapur 250. THE DOPAMINE HYPOTHESIS OF SCHIZOPHRENIA-ALIVE, WELL AND MOVING AHEAD S. Kapurl, P. Seemanl, J. Joyce2, M. Laruelle3 & A. Breier4 I’rheClarkeInstituteof Psychiatryand Universityof Toronto;2 Sun HealthResearchInstitute,Sun City; 3ColumbiaUniversity,New York; 4EliLilly and Company,Indianapolis While the cause of schizophreniaremainsunclear,abnormalitiesin the dopamine systems are the best documentedand show the greatest explanatorypower regardingthe pathophysiologyand therapeuticsof schizophrenia.The symposiumwillpresentdatafroma post-mortemand functionalneoroimagingperspectiveswith an emphasison convergence betweenthe differentstreamsof evidence. Dr.Joycewillpresentdatatiompost-mortemstudiesin schizophrenia, with a spciaf fccusontheanatomicaldistribution, expressionanddevelopmental regulationof thedopamineD3receptoranditsimplicationin thePatholo= of schizophrenia.Dr. Lamellewill presentdata from SPECTshrdiesof presynapticdopaminereleasewhichshowthat patientswithschizophrenia havea dyaregolationof dopaminereleasein responseto exogenouspharmacologicalchallengesandprehminaryevidencethatthisdysmgulation may be accompaniedby changesin baselinedopaminelevels.Dr. Breierwill presentdata demonstratingthat ketamine,a glutamatergicantagonist,inducespsychoticsymptomsvia dismptionof prefrontalconnectionsassociated withincreases in striataldoparninelevels.Dr. KapurwiflshowPET datato suggestthatdoparnineD2receptorblockadeis a necessarycondition for antipsychoticresponse,andallcurrentantipsychotics, typicrdas wellas atypical,inducedopaminereceptorblockade,afbeitto varyingdegme.s.The formaltalkswillendwiththe presentationof dataandan overallsynthesis by Dr. Seeman,followedby a moderateddiscussionbetweenthe audience andthe symposiumpanelists.
New Perspectives in the Basic and Clinical Pharmacology of Cannabinoidergic Systems Saturday,May 30, 12:15 PM-2:15 PM, Location: Pier 8 Chairperson: Cyril D’Souza 251. NEW PERSPECTIVES IN THE BASIC AND CLINICAL PHARMACOLOGY OF CANNABINOIDERGIC SYSTEMS D.C. D’Souzal, S.A. Deadwyle#, S.J. Heishman3, J.-F. M6nard4 & R.J. Mathew5 IDepartmentof Psychiatry,Yale UniversitySchoolof Medicine;‘The BowmanGray Schoolof Medicine,Wake ForestUniversity;3Clinical PharmacologyBranch,NIDAAddictionResearchCenter,4Sanoti Research,SanotiPharmaceuticals;5Departmentof Psychiahy,Duke UniversityMedicalCenter Untilrecently,the molecularbasis of cannabinoidactivityremainedan enigma.The developmentof potent syntheticcarmabinoidskxl to the discoveryof brain cannabinoidreceptors.The cloningof humanbrain carrnabinoidreceptors(CB-R1),the identificationof a secondmessenger systemandputativeendogenousligand,haveled to a renewedinterestin
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the field. These advancesalong with the developmentof a selective cannabinoidantagonisthaveshedfurtherlighton braincarrnabinoidergic systems.Whilebraincarmabinoidergicsystemsare of obviousrelevance to substanceabuse disorders,the functionaland anatomicaldomainof thesesystemssuggestthatbraincarmabinoidergicsystemsmayalsohave relevance in a variety of physiologicaland pathologicalprocesses includinglearning& memory,movementdisordersand psychosis. The gordof this symposiumis to providean updateaboutseveralbasic and clinicalaspectsof cannabinoidergicsystems.Recentfindingsabout the functionaland arratomicafdomainof carmabinoidreceptorsand the cellular mechanismsof action of cannabinoidswill be discussed.The preclinicalpharmacologyof a new highlyselectivecarmabinoidantagonist will also be discussed.lle cognitiveeffects of acute cannabis intoxicationin cannabis abusers will be presented with emphasis on recent pharmacokinetic/pharmacodynamic tindings. IntravenousTHC apwars to produceglobalandfocalincreasesin cerebralbloodflow.‘rite effects of THC on cerebral blood flow (015 PET), behavioral and neurophysiological measureswill be presented.Finally,the relevanceof carmabinoidergicsystems to the neurobiologyof psychosis will be discussedbased on recent tindingsthat in healthyindividuals,intravenous THC producedbehavioraland cognitivesymptomssimilar to the symptomsof schizophrenia.
PAST-PRESIDENT’S WORKSHOP Clinical Diagnosis of Subtle Forms of Depression: Bipolar II and Dysthymic Disorder Saturday, May 30, 12:15 PM-2:15 PM, Location: Dockside 1 Chairperson: David L. Dunner
PAST-PRESIDENT’S WORKSHOP Brain and Mind in Schizophrenia Research Saturday, May 30, 12:15 PM-2:15 PM, Location: Pier 9 Chairperson: Gerald J. Sarwer-Foner
SYMPOSIA Antidepressant Effects of rTMS: Who, How and Why Saturday, May 30, 2:30 PM-5:00 PM, Location: Harbour B Chairperson: Harold A. Sackheim, Co-Chairperson: Mark S. George 252. DOES TMS HAVE BIPOLAR EFFICACY IN BOTH DEPRESSION AND MANIA? R.H. Belmaker & N. Grisaru Ministryof HealthMentalHealthCenter,Facultyof HealthSciences, Ben GurionUniversityof the Negev,Beersheva,Israel Uncontrolled(Grisaruet af, 1994;Georgeet al, 1995)and controlled studies(Georgeet af, in press;Pascurd-Leoneet al, 1996)havereported
The Dopamine Hypothesis of SchizophreniaAlive, Well, and Moving Ahead Saturday,May 30, 12:15 PM-2:15 PM, Location Pier 7 Chairperson:Shitij Kapur 250. THE DOPAMINE HYPOTHESIS OF SCHIZOPHRENIA-ALIVE, WELL AND MOVING AHEAD S. Kapurl, P. Seemanl, J. Joyce2, M. Laruelle3 & A. Breier4 I’rheClarkeInstituteof Psychiatryand Universityof Toronto;2 Sun HealthResearchInstitute,Sun City; 3ColumbiaUniversity,New York; 4EliLilly and Company,Indianapolis While the cause of schizophreniaremainsunclear,abnormalitiesin the dopamine systems are the best documentedand show the greatest explanatorypower regardingthe pathophysiologyand therapeuticsof schizophrenia.The symposiumwillpresentdatafroma post-mortemand functionalneoroimagingperspectiveswith an emphasison convergence betweenthe differentstreamsof evidence. Dr.Joycewillpresentdatatiompost-mortemstudiesin schizophrenia, with a spciaf fccusontheanatomicaldistribution, expressionanddevelopmental regulationof thedopamineD3receptoranditsimplicationin thePatholo= of schizophrenia.Dr. Lamellewill presentdata from SPECTshrdiesof presynapticdopaminereleasewhichshowthat patientswithschizophrenia havea dyaregolationof dopaminereleasein responseto exogenouspharmacologicalchallengesandprehminaryevidencethatthisdysmgulation may be accompaniedby changesin baselinedopaminelevels.Dr. Breierwill presentdata demonstratingthat ketamine,a glutamatergicantagonist,inducespsychoticsymptomsvia dismptionof prefrontalconnectionsassociated withincreases in striataldoparninelevels.Dr. KapurwiflshowPET datato suggestthatdoparnineD2receptorblockadeis a necessarycondition for antipsychoticresponse,andallcurrentantipsychotics, typicrdas wellas atypical,inducedopaminereceptorblockade,afbeitto varyingdegme.s.The formaltalkswillendwiththe presentationof dataandan overallsynthesis by Dr. Seeman,followedby a moderateddiscussionbetweenthe audience andthe symposiumpanelists.
New Perspectives in the Basic and Clinical Pharmacology of Cannabinoidergic Systems Saturday,May 30, 12:15 PM-2:15 PM, Location: Pier 8 Chairperson: Cyril D’Souza 251. NEW PERSPECTIVES IN THE BASIC AND CLINICAL PHARMACOLOGY OF CANNABINOIDERGIC SYSTEMS D.C. D’Souzal, S.A. Deadwyle#, S.J. Heishman3, J.-F. M6nard4 & R.J. Mathew5 IDepartmentof Psychiatry,Yale UniversitySchoolof Medicine;‘The BowmanGray Schoolof Medicine,Wake ForestUniversity;3Clinical PharmacologyBranch,NIDAAddictionResearchCenter,4Sanoti Research,SanotiPharmaceuticals;5Departmentof Psychiahy,Duke UniversityMedicalCenter Untilrecently,the molecularbasis of cannabinoidactivityremainedan enigma.The developmentof potent syntheticcarmabinoidskxl to the discoveryof brain cannabinoidreceptors.The cloningof humanbrain carrnabinoidreceptors(CB-R1),the identificationof a secondmessenger systemandputativeendogenousligand,haveled to a renewedinterestin
BIOLPSYCHL4TRY 1998;43:1S–133S
75s
the field. These advancesalong with the developmentof a selective cannabinoidantagonisthaveshedfurtherlighton braincarrnabinoidergic systems.Whilebraincarmabinoidergicsystemsare of obviousrelevance to substanceabuse disorders,the functionaland anatomicaldomainof thesesystemssuggestthatbraincarmabinoidergicsystemsmayalsohave relevance in a variety of physiologicaland pathologicalprocesses includinglearning& memory,movementdisordersand psychosis. The gordof this symposiumis to providean updateaboutseveralbasic and clinicalaspectsof cannabinoidergicsystems.Recentfindingsabout the functionaland arratomicafdomainof carmabinoidreceptorsand the cellular mechanismsof action of cannabinoidswill be discussed.The preclinicalpharmacologyof a new highlyselectivecarmabinoidantagonist will also be discussed.lle cognitiveeffects of acute cannabis intoxicationin cannabis abusers will be presented with emphasis on recent pharmacokinetic/pharmacodynamic tindings. IntravenousTHC apwars to produceglobalandfocalincreasesin cerebralbloodflow.‘rite effects of THC on cerebral blood flow (015 PET), behavioral and neurophysiological measureswill be presented.Finally,the relevanceof carmabinoidergicsystems to the neurobiologyof psychosis will be discussedbased on recent tindingsthat in healthyindividuals,intravenous THC producedbehavioraland cognitivesymptomssimilar to the symptomsof schizophrenia.
PAST-PRESIDENT’S WORKSHOP Clinical Diagnosis of Subtle Forms of Depression: Bipolar II and Dysthymic Disorder Saturday, May 30, 12:15 PM-2:15 PM, Location: Dockside 1 Chairperson: David L. Dunner
PAST-PRESIDENT’S WORKSHOP Brain and Mind in Schizophrenia Research Saturday, May 30, 12:15 PM-2:15 PM, Location: Pier 9 Chairperson: Gerald J. Sarwer-Foner
SYMPOSIA Antidepressant Effects of rTMS: Who, How and Why Saturday, May 30, 2:30 PM-5:00 PM, Location: Harbour B Chairperson: Harold A. Sackheim, Co-Chairperson: Mark S. George 252. DOES TMS HAVE BIPOLAR EFFICACY IN BOTH DEPRESSION AND MANIA? R.H. Belmaker & N. Grisaru Ministryof HealthMentalHealthCenter,Facultyof HealthSciences, Ben GurionUniversityof the Negev,Beersheva,Israel Uncontrolled(Grisaruet af, 1994;Georgeet al, 1995)and controlled studies(Georgeet af, in press;Pascurd-Leoneet al, 1996)havereported