title: Midbrain dopamine and prefrontal function in humans: interaction and modulation by COMT genotype.
abstract: Using multimodal neuroimaging in humans, we demonstrate specific interactions between prefrontal activity and midbrain dopaminergic synthesis. A common V(108/158)M substitution in the gene for catecholamine-O-methyltransferase (COMT), an important enzyme regulating prefrontal dopamine turnover, predicted reduced dopamine synthesis in midbrain and qualitatively affected the interaction with prefrontal cortex. These data implicate a dopaminergic tuning mechanism in prefrontal cortex and suggest a systems-level mechanism for cognitive and neuropsychiatric associations with COMT.
authors.affiliation: Section on Integrative Neuroimaging, National Institute for Mental Health, National Institutes of Health, Department of Health and Human Services, 9000 Rockville Pike, Bethesda, Maryland 20892-1365, USA. andreasml@nih.gov
authors.forename: Andreas
authors.initials: A
authors.lastname: Meyer-Lindenberg
authors.forename: Philip D
authors.initials: PD
authors.lastname: Kohn
authors.forename: Bhaskar
authors.initials: B
authors.lastname: Kolachana
authors.forename: Shane
authors.initials: S
authors.lastname: Kippenhan
authors.forename: Aideen
authors.initials: A
authors.lastname: McInerney-Leo
authors.forename: Robert
authors.initials: R
authors.lastname: Nussbaum
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Weinberger
authors.forename: Karen Faith
authors.initials: KF
authors.lastname: Berman
mesh_terms: D000328:Adult; D019943:Amino Acid Substitution / Q000235:genetics; D001931:Brain Mapping; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D003071:Cognition / Q000502:physiology*; D004298:Dopamine / Q000378:metabolism*; D005246:Feedback / Q000502:physiology; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008570:Memory, Short-Term / Q000502:physiology; D008636:Mesencephalon / Q000000981:diagnostic imaging / Q000201:enzymology*; D008657:Metabolic Clearance Rate / Q000502:physiology; D009434:Neural Pathways / Q000000981:diagnostic imaging / Q000201:enzymology*; D009483:Neuropsychological Tests; D049268:Positron-Emission Tomography; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging / Q000201:enzymology*; D011930:Reaction Time / Q000235:genetics; D009435:Synaptic Transmission / Q000502:physiology
chemical_list: D002394:Catechol O-Methyltransferase; D004298:Dopamine