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Comparative Study
. 2005 May 18;25(20):5038-45.
doi: 10.1523/JNEUROSCI.0476-05.2005.

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

Giuseppe Blasi  1 , Venkata S Mattay, Alessandro Bertolino, Brita Elvevåg, Joseph H Callicott, Saumitra Das, Bhaskar S Kolachana, Michael F Egan, Terry E Goldberg, Daniel R Weinberger
Affiliations
Comparative Study

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

Giuseppe Blasi et al. J Neurosci. .

Abstract

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 COMT val158met polymorphism 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-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.

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Figures

Figure 1.
Figure 1.
VAC task. See Materials and Methods for explanation.
Figure 2.
Figure 2.
Effect of COMT genotype on accuracy during the VAC task. A statistically significant effect of COMT genotype was found on accuracy (percentage correct) only at the highest level of attentional control. A met allele load effect was found with individuals homozygous for the met allele performing significantly better than the val/met (vm) heterozygotes and the val/val (vv) homozygotes. mm, met/met. Error bars represent SEM.
Figure 3.
Figure 3.
Effect of attentional load and COMT genotype on BOLD response during the VAC task. There were main effects of increasing level of attentional control (A) and COMT genotype (B) and a significant interaction between increasing level of attentional control and COMT genotype (C) on brain activation during the VAC task (p < 0.05; FWE rate, corrected). A, In addition to the dorsal cingulate, the dorsolateral prefrontal cortex, premotor, and supplementary motor areas showed a main effect of increasing level of attentional control. B, The main effect of COMT genotype (val/val > val/met > met/met) was restricted only to the dorsal cingulate [local maxima in BA24 (-4, -2, 41)]. Note that the local maxima for the cluster that showed a significant COMT genotype by level of attentional control is similar to the one that showed a main effect of COMT genotype [BA24 (-4, -2, 41].
Figure 4.
Figure 4.
Effect of COMT genotype on BOLD response at intermediate and high demands of the VAC task. There was a main effect of COMT genotype (val/val > val/met > met/met) on brain activation during the VAC task (p < 0.001, uncorrected). A, High demand [local maxima in BA24 (-8, -2, 41)]. B, Intermediate demand [local maxima in BA24 (-4, -2, 41)].
Figure 5.
Figure 5.
BOLD signal change in dorsal cingulate during the VAC task. For illustrative purposes, BOLD signal change is plotted from a representative voxel in the cluster in BA24/32 that showed a significant interaction for COMT genotype by increasing level of attentional control. vv, val/val; vm, val/met; mm, met/met.
See this image and copyright information in PMC

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