A Functional Polymorphism in the COMT Gene and Performance on a Test of Prefrontal Cognition

Unit of Molecular Psychiatry, Hillside Hospital, Glen Oaks, NY 11004, USA.
American Journal of Psychiatry (Impact Factor: 12.3). 05/2002; 159(4):652-4. DOI: 10.1176/appi.ajp.159.4.652
Source: PubMed


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.
Val158Met was genotyped in 73 healthy volunteers. A task of prefrontal cognition, the Wisconsin Card Sorting Test, was also administered.
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.
These data are consistent with those of previous studies, suggesting that a functional genetic polymorphism may influence prefrontal cognition.

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    • "Conversely, genetic conditions of reduced COMT activity, which translate into increased cortical dopamine, produce a selective improvement on EDS abilities in mice (Scheggia et al., 2014). These results closely parallel findings in healthy humans and patients with schizophrenia showing that COMT Val carriers have impaired performance and a higher number of perseverative errors in the EDS phase of the WCST and/or the CANTAB ID/ED task compared with individuals with two copies of the COMT Met allele (Egan et al., 2001;Joober et al., 2002;Malhotra et al., 2002;Mattay et al., 2003). Furthermore, the schizophrenia-relevant animal model of chronic administration of phencyclidine, show selective EDS impairments in the attentional set-shifting tasks in both mice and rats (Egerton, Reid, McKerchar, Morris, & Pratt, 2005;Scheggia et al., 2014). "
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    • "The functional Val108/158 Met polymorphism in COMT 153 accounts for a 4-fold variation in enzyme activity and dopamine catabolism. It has been shown to 154 affect executive cognition and frontal lobe function has been linked to neuronal activation in the 155 working memory cortical network, including the prefrontal cortex (Egan et al., 2001; Joober et al., 156 2002; Malhotra et al., 2002; Goldberg et al., 2003; Bertolino et al., 2006a). Associations between 157 genetic variability in the COMT gene and working memory have, however, not been consistent with 158 some studies finding no such link (Stefanis et al., 2004) and others reporting associations only for 159 more difficult working memory tasks such as the 2-back compared to the 0-back task (Goldberg et al., 160 2003). "
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    • " val ) with Methionine ( met ) allele at this codon ( G to A ) results in reduced COMT enzymatic activity , which leads to less dopamine degradation and higher prefrontal dopamine availability ( Chen et al . , 2004 ) . COMT met homozygotes show comparatively better performance in working memory tasks and other measures of executive function ( cf . Malhotra et al . , 2002 ) . In addition to COMT val158met , the DRD2 G > T polymorphism influences dopamine availability by regulating the expression of striatal dopamine receptors . D2 receptor activity in the striatum has been associated with motor control , coordination , and error avoidance ( Xu et al . , 2007 ; Doll et al . , 2011 ) . The T allele of the "
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