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Publications [#221645] of Ahmad Hariri

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Journal Articles

  1. Drabant, E. M. and Hariri, A. R. and Meyer-Lindenberg, A. and Munoz, K. E. and Mattay, V. S. and Kolachana, B. S. and Egan, M. F. and 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--406. [17146014], [doi]
    (last updated on 2013/12/23)

    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.

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