Gene–environment interaction on cognition: A twin study of childhood maltreatment and COMT variability

The functional variant Val158Met in the coding sequence of COMT gene is involved in the modulation of dopamine availability in the prefrontal cortex in both clinical and general population samples. It has been suggested that the interplay between this genotype and early environmental factors could be used to predict the observed variation in cognitive flexibility. However, other genetic variants and environmental factors may confound the association and produce the inconsistent results commonly found in the literature. In the present study we aimed at testing putative interaction mechanisms between childhood maltreatment and COMT genotypic variability that might explain a proportion of the observed variability of cognitive flexibility in the population. Our design was based on a sample of adult monozygotic twins, which allowed us to test these effects free from potential genetic and shared-environmental confounding factors. Results showed that unique environmental effects of childhood maltreatment significantly impacted cognitive performance among Met/Met subjects. Interestingly, the direction of the association indicated that exposure to early stressful experiences was associated with enhanced cognitive flexibility in this genotype group. These results suggest that COMT may operate as a plasticity gene that provides differential cognitive capacity to respond to environmental stressors.