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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    • "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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    • "A later study, however, found that healthy controls homozygous for the met allele demonstrated better performance on a cognitive task of executive functioning (Trail-Making Test) (Wishart et al., 2011). Other studies have shown that healthy control subjects homozygous for the Met allelic variant exhibited better performance on tasks of working memory and the Wisconsin Card Sorting Task compared to subjects homozygous for Val (Malhotra et al., 2002; Rosa et al., 2004). Conversely, van Den Bos et al., (2009) found that healthy control female subjects who were Met/Met homozygous chose more disadvantageously on the Iowa Gambling Task than subjects homozygous for valine (Val/Val). "
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    ABSTRACT: Neuropsychological studies of adults with problem gambling indicate impairments across multiple cognitive domains. Catechol-O-methyltransferase (COMT) plays a unique role in the regulation of dopamine in the prefrontal cortex, and has been implicated in the cognitive dysfunction evident in problem gambling. This study examined adults with varying levels of gambling behavior to determine whether COMT genotype was associated with differences in gambling symptoms and cognitive functioning. 260 non-treatment-seeking adults aged 18-29 years with varying degrees of gambling behavior provided saliva samples for genotyping COMT val158met (rs4680). All subjects underwent clinical evaluations and neurocognitive assessment of decision-making, working memory, and impulsivity. The Val/Val COMT genotype was associated with the largest percentage of subjects with gambling disorder (31.8%), a rate significantly different from the Val/Met (13.2%) group (p = 0.001). The Val/Val COMT group was also associated with significantly more gambling disorder diagnostic criteria being met, greater frequency of gambling behavior, and significantly worse cognitive performance on the Cambridge Gamble Task (risk adjustment and delay aversion) and the Spatial Working Memory task (total errors). This study adds to the growing literature on the role of COMT in impulsive behaviors by showing that the Val/Val genotype was associated with specific clinical and cognitive elements among young adults who gamble, in the absence of differences on demographic measures and other cognitive domains. Future work should consider using genotyping to explore whether certain polymorphisms predict subsequent development of impulsive behaviors including gambling disorder, and treatment outcomes. Copyright © 2015 Elsevier Ltd. All rights reserved.
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