COMT Val158met genotype and individual differences in executive function in healthy adults

Heather A. Wishart, Robert M. Roth, Andrew J. Saykin, C. Harker Rhodes, Gregory J. Tsongalis, Kristine A. Pattin, Jason H. Moore, Thomas W. McAllister

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53 Scopus citations


The Val158Met polymorphism of the catechol-O-methyltransferase (COMT) gene may be related to individual differences in cognition, likely via modulation of prefrontal dopamine catabolism. However, the available studies have yielded mixed results, possibly in part because they do not consistently account for other genes that affect cognition. We hypothesized that COMT Met allele homozygosity, which is associated with higher levels of prefrontal dopamine, would predict better executive function as measured using standard neuropsychological testing, and that other candidate genes might interact with COMT to modulate this effect. Participants were 95 healthy, right-handed adults who underwent genotyping and cognitive testing. COMT genotype predicted executive ability as measured by the Trail-Making Test, even after covarying for demographics and Apolipoprotein E (APOE), brain-derived neurotrophic factor (BDNF), and ankyrin repeat and kinase domain containing 1 (ANKK1) genotype. There was a COMT-ANKK1 interaction in which individuals having both the COMT Val allele and the ANKK1 T allele showed the poorest performance. This study suggests the heterogeneity in COMT effects reported in the literature may be due in part to gene-gene interactions that influence central dopaminergic systems. (JINS, 2011, 17, 174-180)

Original languageEnglish (US)
Pages (from-to)174-180
Number of pages7
JournalJournal of the International Neuropsychological Society
Issue number1
StatePublished - Jan 1 2011



  • Catechol-O- methyltransferase
  • Epistasis
  • Executive control
  • Neuropsychological tests
  • ognition
  • Polymorphism

ASJC Scopus subject areas

  • Clinical Neurology
  • Psychiatry and Mental health
  • Clinical Psychology
  • Neuroscience(all)

Cite this

Wishart, H. A., Roth, R. M., Saykin, A. J., Rhodes, C. H., Tsongalis, G. J., Pattin, K. A., Moore, J. H., & McAllister, T. W. (2011). COMT Val158met genotype and individual differences in executive function in healthy adults. Journal of the International Neuropsychological Society, 17(1), 174-180.