Effect of Catechol-O-Methyltransferaseval158metGenotype on Attentional Control

• DOI: 10.1523/jneurosci.0476-05.2005
• Publication Date: 2005-05-18T18:28:49Z
• Authors: 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
• Keywords: Adult; Male; Genotype; catechol-O-methyltransferase; 150; Prefrontal Cortex; Neuropsychological Tests; Catechol O-Methyltransferase; dorsal cingulate; 03 medical and health sciences; Methionine; 0302 clinical medicine; Image Processing, Computer-Assisted; Reaction Time; Humans; genetics; Attention; cognitive control; Analysis of Variance; Brain Mapping; Polymorphism, Genetic; fMRI; variable attentional control task; Magnetic Resonance Imaging; attention; Oxygen; Case-Control Studies; Regression Analysis; Female; dopamine; Photic Stimulation

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 (val158met) 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 COMTval158metpolymorphism also affects the function of the cingulate during AC. Individuals homozygous for the high-activity valine (“val”) 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-activitymetallele, and these effects are most evident at the highest demand for AC. These results indicate thatmetallele load and presumably enhanced dopaminergic tone improve the “efficiency” of local circuit processing within the cingulate cortex and thereby its function during AC.