[Dopamine system genes interaction and neurocognitive traits in patients with schizophrenia, their relatives and...

To elucidate main effects of dopamine receptor D4 (DRD4) and cathecol-O-methyltransferase (COMT) genes as well as their interaction effect on neurocognitive traits, DRD4 gene polymorphisms (-809G/A, -521C/T) and the COMT gene Val158Met polymorphism, along with characteristics of verbal memory, executive functions and peculiarities of associative processes, have been studied in 150 patients with schizophrenia, 83 their relatives and 118 mentally healthy subjects without positive family history of psychosis. A main effect of -521C/T polymorphism and DRD4 (-521C/T).Vall58Met polymorphisms interaction were found for verbal fluency, carriers of the Val/Val+CC and the Met/Met+TT genotypes performing better on this task as compared to other genotypes. An interaction DRD4 (-521C/T).Val158Met effect on originality of speech associations was observed in the combined group of unaffected individuals (relatives and controls), with lower scores of the trait in those with the Met/Met+CC genotype. The COMT-DRD4 (-809G/A) interaction effect on working memory was demonstrated for patients and unaffected individuals, homozygotes for the Val and the G alleles having the best results and homozygotes for the Met and the A alleles--the worst ones. The data obtained suggest the relationship of DRD4 and COMT genes with different characteristics of executive functions but not with verbal memory.