Catechol O-methyltransferase val158met genotype and neural mechanisms related to affective arousal and regulation.

Published

Journal Article

CONTEXT: Catechol O-methyltransferase (COMT), the major enzyme determining cortical dopamine flux, has a common functional polymorphism (val(158)met) that affects prefrontal function and working memory capacity and has also been associated with anxiety and emotional dysregulation. OBJECTIVES: To examine COMT val(158)met effects on corticolimbic circuitry reactivity and functional connectivity during processing of biologically salient stimuli, as well as the relationship to the temperamental trait of novelty seeking. DESIGN: Within-subject functional magnetic resonance imaging study. SETTING: National Institute of Mental Health, Genes, Cognition, and Psychosis Program, Bethesda, Md. Patients One hundred one healthy subjects of both sexes. RESULTS: We found that the met allele was associated with a dose-dependent increase in hippocampal formation and ventrolateral prefrontal cortex activation during viewing of faces displaying negative emotion. In met/met homozygotes, limbic and prefrontal regions showed increased functional coupling. Moreover, in these same subjects, the magnitude of amygdala-orbitofrontal coupling was inversely correlated with novelty seeking, an index of temperamental inflexibility. CONCLUSIONS: Our results indicate that heritable variation in dopamine neurotransmission associated with the met allele of the COMT polymorphism results in heightened reactivity and connectivity in corticolimbic circuits. This may reflect a genetic predisposition for inflexible processing of affective stimuli, a mechanism possibly accounting for aspects of arousal and behavioral control that contribute to emotional dysregulation previously reported in met/met individuals.

Full Text

Duke Authors

Cited Authors

  • Drabant, EM; Hariri, AR; Meyer-Lindenberg, A; Munoz, KE; Mattay, VS; Kolachana, BS; Egan, MF; Weinberger, DR

Published Date

  • December 2006

Published In

Volume / Issue

  • 63 / 12

Start / End Page

  • 1396 - 1406

PubMed ID

  • 17146014

Pubmed Central ID

  • 17146014

Electronic International Standard Serial Number (EISSN)

  • 1538-3636

International Standard Serial Number (ISSN)

  • 0003-990X

Digital Object Identifier (DOI)

  • 10.1001/archpsyc.63.12.1396

Language

  • eng