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Review
. 2009 Nov 24;164(1):72-87.
doi: 10.1016/j.neuroscience.2009.05.014. Epub 2009 May 13.

Genes, cognition and brain through a COMT lens

D Dickinson  1 , B Elvevåg
Affiliations
Review

Genes, cognition and brain through a COMT lens

D Dickinson et al. Neuroscience. .

Abstract

Various genes are known to modulate the delicate balance of dopamine in prefrontal cortex and influence cortical information processing. Catechol-O-methyltransferase (COMT) on chromosome 22q11 is the most widely studied of these genes. Val158Met, a common, functional variant in the coding sequence that increases or decreases the enzymatic activity of the gene has been shown to impact the efficiency of prefrontally-mediated cognition, specifically executive functioning, working memory, fluid intelligence and attentional control. We review the rapidly evolving literature exploring the association between COMT genotype and cognitive performance, and illustrate how this polymorphism has served a pivotal role in characterizing various interacting dimensions of complexity in the relationship between genes and cognition. We review how Val158Met has been used to help develop and validate behavioral and neurophysiological phenotypes, as a critical tool in dissecting overlapping neural functional systems and exploring interactions within and between genes, and in exploring how gene effects on cognition are modulated by environmental, demographic and developmental factors. Despite the impressive range of findings, the COMT story is also a bracing reminder of how much work remains to translate this knowledge into practical clinical applications.

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Figures

Figure 1
Figure 1
Wisconsin Card Sort Test (WCST). The task is for the participant to categorize the series of cards (at the bottom) according to an unspoken rule that the experimenter is sorting according to, namely color, shape, size or number.
Figure 2
Figure 2
Variable Attentional Control (VAC) task. Each ‘arrow’ stimulus is composed of arrows of three different sizes (large, medium and small arrows) pointing either to the right or to the left. The direction of the arrows is congruent or incongruent across all three sizes. The task is to respond as quickly as possible to the direction of either the small, medium or big arrows indicated by the cue, namely ‘small’, ‘medium’ or ‘big’.
Figure 3
Figure 3
Inverted ‘U’: Predicted relative effects of COMT genotype and amphetamine on prefrontal cortical function as illustrated by N-back task performance.
See this image and copyright information in PMC

References

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