Interaction of dopamine system genes and cognitive functions in patients with schizophrenia and their relatives and in healthy subjects from the general population.

Linkage between the DRD4 and COMT genes and cognitive measures characterizing verbal memory, executive functions, and associative processes was studied in 150 patients with schizophrenia, 83 of their relatives, and 118 mentally healthy subjects without any family history of psychoses, with the aim of detecting the main effects of the polymorphic markers -809G/A and -521C/T (DRD4) and Val158Met (COMT) when present individually and together. The group of patients showed a main effect for polymorphism -521C/T on verbal fluency and an effect of the interaction of this polymorphism and the COMT gene on this cognitive trait. The highest level of verbal fluency was seen among carriers of the Val/Val+CC and Met/Met+TT genotypes. In the combined group of unaffected individuals, the interaction of the COMT and DRD4 -521C/TT genotypes had an effect on the standardness of speech associations due to a decrease in the standardness of associations in carriers of the Met/Met+CC genotype. Finally, both patients and unaffected individuals showed an effect for the interaction between the COMT and DRD4 -809G/A genotypes on working memory. Patients and healthy subjects showed similar features: the highest values were seen in subjects homozygous for the Val and G alleles, while the lowest values were seen in homozygotes for the Met and A alleles. These data provide evidence for a relationship between the DRD4 and COMT genes and different aspects of executive functions and the absence of such a relationship in relation to verbal memory.