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

Andreas Meyer-Lindenberg, Philip D. Kohn, Bhaskar Kolachana, Shane Kippenhan, Aideen McInerney-Leo, Robert Nussbaum, Daniel R. Weinberger, Karen Faith Berman

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)594-596
Number of pages3
JournalNature neuroscience
Volume8
Issue number5
DOIs
StatePublished - May 2005
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)

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