TY - JOUR

T1 - Interaction of COMT val 158met and externalizing behavior

T2 - Relation to prefrontal brain activity and behavioral performance

AU - Shehzad, Zarrar

AU - DeYoung, Colin G.

AU - Kang, Yoona

AU - Grigorenko, Elena L.

AU - Gray, Jeremy R.

N1 - 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.).

PY - 2012/5/1

Y1 - 2012/5/1

N2 - 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.

AB - 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.

KW - COMT

KW - Externalizing

KW - FMRI

KW - Genetics

KW - Inhibitory control

KW - MSIT

UR - http://www.scopus.com/inward/record.url?scp=84858710622&partnerID=8YFLogxK

U2 - 10.1016/j.neuroimage.2012.01.097

DO - 10.1016/j.neuroimage.2012.01.097

M3 - Article

C2 - 22306803

AN - SCOPUS:84858710622

VL - 60

SP - 2158

EP - 2168

JO - NeuroImage

JF - NeuroImage

SN - 1053-8119

IS - 4

ER -