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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.

COMT Val 108/158 Met Genotype Affects Neural but not Cognitive Processing in Healthy Individuals