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

Publication ,  Journal Article
Drabant, EM; Hariri, AR; Meyer-Lindenberg, A; Munoz, KE; Mattay, VS; Kolachana, BS; Egan, MF; Weinberger, DR
Published in: Archives of general psychiatry
December 2006

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.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.Within-subject functional magnetic resonance imaging study.National Institute of Mental Health, Genes, Cognition, and Psychosis Program, Bethesda, Md. Patients One hundred one healthy subjects of both sexes.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.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.

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Published In

Archives of general psychiatry

DOI

EISSN

1538-3636

ISSN

0003-990X

Publication Date

December 2006

Volume

63

Issue

12

Start / End Page

1396 / 1406

Related Subject Headings

  • Visual Perception
  • Valine
  • Temperament
  • Synaptic Transmission
  • Psychiatry
  • Prefrontal Cortex
  • Polymorphism, Genetic
  • Oxygen
  • Neural Pathways
  • Methionine
 

Citation

APA
Chicago
ICMJE
MLA
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Drabant, E. M., Hariri, A. R., Meyer-Lindenberg, A., Munoz, K. E., Mattay, V. S., Kolachana, B. S., … Weinberger, D. R. (2006). Catechol O-methyltransferase val158met genotype and neural mechanisms related to affective arousal and regulation. Archives of General Psychiatry, 63(12), 1396–1406. https://doi.org/10.1001/archpsyc.63.12.1396
Drabant, Emily M., Ahmad R. Hariri, Andreas Meyer-Lindenberg, Karen E. Munoz, Venkata S. Mattay, Bhaskar S. Kolachana, Michael F. Egan, and Daniel R. Weinberger. “Catechol O-methyltransferase val158met genotype and neural mechanisms related to affective arousal and regulation.Archives of General Psychiatry 63, no. 12 (December 2006): 1396–1406. https://doi.org/10.1001/archpsyc.63.12.1396.
Drabant EM, Hariri AR, Meyer-Lindenberg A, Munoz KE, Mattay VS, Kolachana BS, et al. Catechol O-methyltransferase val158met genotype and neural mechanisms related to affective arousal and regulation. Archives of general psychiatry. 2006 Dec;63(12):1396–406.
Drabant, Emily M., et al. “Catechol O-methyltransferase val158met genotype and neural mechanisms related to affective arousal and regulation.Archives of General Psychiatry, vol. 63, no. 12, Dec. 2006, pp. 1396–406. Epmc, doi:10.1001/archpsyc.63.12.1396.
Drabant EM, Hariri AR, Meyer-Lindenberg A, Munoz KE, Mattay VS, Kolachana BS, Egan MF, Weinberger DR. Catechol O-methyltransferase val158met genotype and neural mechanisms related to affective arousal and regulation. Archives of general psychiatry. 2006 Dec;63(12):1396–1406.

Published In

Archives of general psychiatry

DOI

EISSN

1538-3636

ISSN

0003-990X

Publication Date

December 2006

Volume

63

Issue

12

Start / End Page

1396 / 1406

Related Subject Headings

  • Visual Perception
  • Valine
  • Temperament
  • Synaptic Transmission
  • Psychiatry
  • Prefrontal Cortex
  • Polymorphism, Genetic
  • Oxygen
  • Neural Pathways
  • Methionine