Midbrain dopamine and prefrontal function in humans: interaction and modulation by COMT genotype

• Published in: Nature neuroscience Vol. 8; no. 5; pp. 594 - 596
• Main Authors: Meyer-Lindenberg, Andreas, Kohn, Philip D, Kolachana, Bhaskar, Kippenhan, Shane, McInerney-Leo, Aideen, Nussbaum, Robert, Weinberger, Daniel R, Berman, Karen Faith
• Format: Journal Article
• Language: English
• Published: United States Nature Publishing Group 01.05.2005
• Subjects: Adult; Amino Acid Substitution - genetics; Brain Mapping; Catechol O-Methyltransferase - genetics; Cognition - physiology; Dopamine; Dopamine - metabolism; Feedback - physiology; Female; Genotype; Humans; Male; Memory, Short-Term - physiology; Mesencephalon; Mesencephalon - diagnostic imaging; Mesencephalon - enzymology; Metabolic Clearance Rate - physiology; Neural Pathways - diagnostic imaging; Neural Pathways - enzymology; Neuropsychological Tests; Physiological aspects; Positron-Emission Tomography; Prefrontal cortex; Prefrontal Cortex - diagnostic imaging; Prefrontal Cortex - enzymology; Reaction Time - genetics; Synaptic Transmission - physiology; United States
• ISSN: 1097-6256; 1546-1726
• DOI: 10.1038/nn1438

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.