Interaction of COMT val 158met and externalizing behavior: Relation to prefrontal brain activity and behavioral performance

Zarrar Shehzad, Colin G. DeYoung, Yoona Kang, Elena L. Grigorenko, Jeremy R. Gray

    Research output: Contribution to journalArticlepeer-review

    26 Scopus citations


    A promising approach in neuroimaging studies aimed at understanding effects of single genetic variants on behavior is the study of gene-trait interactions. Variation in the catechol-O-methyl-transferase gene (COMT) is associated with the regulation of dopamine levels in the prefrontal cortex and with cognitive functioning. Given the involvement of dopaminergic neurotransmission in externalizing behavior, a trait characterized by impulsivity and aggression, especially in men, externalizing (as a trait) may index a set of genetic, environmental, and neural characteristics pertinent to understanding phenotypic effects of genetic variation in the COMT gene. In the current study, we used a gene-trait approach to investigate effects of the COMT val 158met polymorphism and externalizing on brain activity during moments involving low or high demands on cognitive control. In 104 male participants, interference-related activation depended conjointly on externalizing and val 158met: stronger activation in the dorsal anterior cingulate and lateral prefrontal cortex was found for val/val individuals with high trait externalizing while stronger activation in cingulate motor areas and sensorimotor precuneus was found for met/met individuals with low externalizing. Our results suggest that the val/val genotype, coupled with high levels of trait externalizing, lowers the efficiency of stimulus conflict resolution, whereas the met/met genotype, coupled with low levels of externalizing, lowers the efficiency of response selection.

    Original languageEnglish (US)
    Pages (from-to)2158-2168
    Number of pages11
    Issue number4
    StatePublished - May 1 2012

    Bibliographical note

    Funding Information:
    This work was supported by the National Institute of Mental Health ( F32 MH077382 to C.G.D.), the National Science Foundation ( DRL 0644131 to J.R.G.), and a Natural Sciences and Engineering Research Council of Canada Post-Graduate Scholarship (to Z.S.).


    • COMT
    • Externalizing
    • FMRI
    • Genetics
    • Inhibitory control
    • MSIT

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