A functional polymorphism in the COMT gene and performance on a test of prefrontal cognition

Am J Psychiatry. 2002 Apr;159(4):652-4. doi: 10.1176/appi.ajp.159.4.652.


Objective: In the prefrontal cortex, the enzyme catechol O-methyltransferase (COMT) is critical in the metabolic degradation of dopamine, a neurotransmitter hypothesized to influence human cognitive function. The COMT gene contains a functional polymorphism, Val158Met, that exerts a fourfold effect on enzyme activity. The current study investigated whether prefrontal cognition varies with COMT genotype.

Method: Val158Met was genotyped in 73 healthy volunteers. A task of prefrontal cognition, the Wisconsin Card Sorting Test, was also administered.

Results: Subjects with only the low-activity met allele made significantly fewer perseverative errors on the Wisconsin Card Sorting Test than did subjects with the val allele.

Conclusions: These data are consistent with those of previous studies, suggesting that a functional genetic polymorphism may influence prefrontal cognition.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Alleles
  • Codon
  • Cognition / physiology*
  • Female
  • Genotype*
  • Humans
  • Male
  • Methionine / genetics
  • Middle Aged
  • Neuropsychological Tests
  • Polymorphism, Genetic / genetics*
  • Prefrontal Cortex / physiology*
  • Reference Values
  • Valine / genetics


  • Codon
  • Methionine
  • Valine