Effect of catechol-O-methyltransferase val158met genotype on attentional control

Giuseppe Blasi, Venkata S. Mattay, Alessandro Bertolino, Brita Elvevåg, Joseph H. Callicott, Saumitra Das, Bhaskar S. Kolachana, Michael F. Egan, Terry E. Goldberg, Daniel R. Weinberger

Research output: Contribution to journalArticlepeer-review

261 Scopus citations


The cingulate cortex is richly innervated by dopaminergic projections and plays a critical role in attentional control (AC). Evidence indicates that dopamine enhances the neurophysiological signal-to-noise ratio and that dopaminergic tone in the frontal cortex is critically dependent on catechol-O-methyltransferase (COMT). A functional polymorphism (val 158met) in the COMT gene accounts for some of the individual variability in executive function mediated by the dorsolateral prefrontal cortex. We explored the effect of this genetic polymorphism on cingulate engagement during a novel AC task. We found that the COMT val158met polymorphism also affects the function of the cingulate during AC. Individuals homozygous for the high-activity valine ("met") allele show greater activity and poorer performance than val/methionine ("met") heterozygotes, who in turn show greater activity and poorer performance than individuals homozygous for the low-activity met allele, and these effects are most evident at the highest demand for AC. These results indicate that met allele load and presumably enhanced dopaminergic tone improve the "efficiency" of local circuit processing within the cingulate cortex and thereby its function during AC.

Original languageEnglish (US)
Pages (from-to)5038-5045
Number of pages8
JournalJournal of Neuroscience
Issue number20
StatePublished - May 18 2005
Externally publishedYes


  • Attention
  • Catechol-O-methyltransferase
  • Cognitive control
  • Dopamine
  • Dorsal cingulate
  • Genetics
  • Variable attentional control task
  • fMRI

ASJC Scopus subject areas

  • Neuroscience(all)


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