Midbrain dopamine and prefrontal function in humans: interaction and modulation by COMT genotype.
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.
Meyer-Lindenberg
Andreas
A
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
Kohn
Philip D
PD
Kolachana
Bhaskar
B
Kippenhan
Shane
S
McInerney-Leo
Aideen
A
Nussbaum
Robert
R
Weinberger
Daniel R
DR
Berman
Karen Faith
KF
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
D002394:Catechol O-Methyltransferase; D004298:Dopamine