COMT Val108/158 Met Genotype Affects Neural but not Cognitive Processing in Healthy Individuals

Abstract

The relationship between cognition and a functional polymorphism in the catechol-O-methlytransferase (COMT) gene, val108/158met, is one of debate in the literature. Furthermore, based on the dopaminergic differences associated with the COMT val108/158met genotype, neural differences during cognition may be present, regardless of genotypic differences in cognitive performance. To investigate these issues the current study aimed to 1) examine the effects of COMT genotype using a large sample of healthy individuals (n = 496-1218) and multiple cognitive measures, and using a subset of the sample (n = 22), 2) examine whether COMT genotype effects medial temporal lobe (MTL) and frontal activity during successful relational memory processing, and 3) investigate group differences in functional connectivity associated with successful relational memory processing. Results revealed no significant group difference in cognitive performance between COMT genotypes in any of the 19 cognitive measures. However, in the subset sample, COMT val homozygotes exhibited significantly decreased MTL and increased prefrontal activity during both successful relational encoding and retrieval, and reduced connectivity between these regions compared with met homozygotes. Taken together, the results suggest that although the COMT val108/158met genotype has no effect on cognitive behavioral measures in healthy individuals, it is associated with differences in neural process underlying cognitive output.

The <b><i>COMT</i></b><b><i>p.Val158Met</i></b> Polymorphism and Cognitive Performance in Adult Development, Healthy Aging and Mild Cognitive Impairment

“…While it is plausible that losses of brain resources such as decline of striatal and extrastriatal dopamine or atrophy affecting the PFC may amplify the effects of genetic polymorphisms such as COMT p.Val158Met on cognition [11], our results show that the COMT genotype on its own is not a determining factor. Further studies have demonstrated inefficient cortical processing as reflected by low performance and greater activity in Val homozygotes compared to Met homozygotes in tasks demanding working memory capacity in participants in their mid-thirties [4,28] and attentional control [29]. Remarkably, neurological differences were sometimes identified in the absence of effects on behavioral measures such as test performance [28], suggesting a compensatory mechanism.…”

“…Further studies have demonstrated inefficient cortical processing as reflected by low performance and greater activity in Val homozygotes compared to Met homozygotes in tasks demanding working memory capacity in participants in their mid-thirties [4,28] and attentional control [29]. Remarkably, neurological differences were sometimes identified in the absence of effects on behavioral measures such as test performance [28], suggesting a compensatory mechanism. Since we did not find an effect of the COMT genotype on cognitive trajectories, we must consider that certain factors related to the birth cohort are determinative rather than age per se.…”

COMT, neuropsychological function and brain structure in schizophrenia: a systematic review and neurobiological interpretation

“…71,72 Performance on the TMT-A has not been found to be associated with the COMT Val 158 Met polymorphism in pa tients with schizophrenia 45,49,56 or healthy individuals. 20,28,56 Worse performance on the TMT-B has been found to be associated with Val/Val and Val/Met genotypes in healthy individ uals in 1 study 20 but not in others, 28,56 nor in those evaluating patients with schizophrenia. 45,49,56 Interestingly, an association between the COMT Val 158 Met polymorphism and worse TMT-B performance has been reported in healthy individuals carrying both the COMT Val allele and the ANKK1 (rs1800497) T allele.…”

COMT genotype, gambling activity, and cognition

“…Another study found that Met subjects outperformed Val subjects on an N-Back working memory task (Farrell et al, 2012), while the same research group also found that the COMT polymorphism affected functional connectivity of the brain in the resting state (Tunbridge et al, 2013). One study found no differences between COMT groups on a battery of 19 cognitive tasks including cognitive flexibility, memory, and visual processing (Dennis et al, 2010). 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).…”