Effects of the Interaction of the ANKK1/DRD2 TaqIA and HTR2C Cys23Ser Polymorphisms on Approach Motivation in Schizophrenia Patients and Healthy People

Abstract

Objective. To assess the association of the DRD2 gene and its interaction with the HTR2C gene with the characteristics of the hedonistic and activatory aspects of approach motivation in schizophrenia. Materials and methods. Genotypes at the polymorphic loci rs1800497 of DRD2 and rs6318 (Cys23Ser) of HTR2C were identified in a cohort including 174 patients with schizophrenia spectrum disorders and 268 healthy subjects. Subjects completed scales assessing approach motivation (BIS/BAS) and the Temporal Experience of Pleasure Scale (TEPS). Results and conclusions. Analysis taking account of sex and age identified an effect of the interaction between the DRD2 and HTR2C genes and diagnosis (p = 0.033) on assessments on the BAS scales. The effect was significant on the Fun-Seeking and Drive subscales. Among patients, the highest scores on both scales were seen with the combination of the DRD2 TT/CT and HTR2C GG/G genotypes and the lowest in carriers of the diplotypes with the minor alleles at both loci. Differences between these group were nominally significant for both scales, but were not significant after correction for multiple comparisons. Among healthy subjects, the highest levels of motivation were seen in people lacking the minor alleles. They were significantly different from those in carriers of the DRD2 TT/CT and HTR2C GG/G diplotype on the Fun-Seeking subscale (pcorr = 0.008). DRD2 and HTR2C were not found to have any effect on TEPS evaluations. Our results can be interpreted as indicating a role for the interaction of the DRD2 and HTR2C genes in the variation of the activatory aspects of approach motivation in both schizophrenia patients and healthy subjects. However, the absence of highly significant (persisting after the Bonferroni correction) differences between groups with different diplotypes makes it difficult to interpret this effect.