Opposite effects of DRD2 gene polymorphisms on inhibitory control and motor output in antisaccade task in healthy subjects and schizophrenia patients.

backgroundDopamine is one of the neurotransmitters that have been implicated in schizophrenia. Researchers suggest that certain D2 receptors (DRD2) gene polymorphisms alter dopaminergic signaling and influence prefrontally-mediated executive functions. The present study aims to test the effects of DRD2 rs6277, rs6275 and rs2242592 polymorphisms on cognitive and motor measures of antisaccade task (AS) in healthy subjects and schizophrenia patients. METHODS AND

resultsIn total 162 male subjects participated in the study, 101 of whom completed AS session. Error rate, mean latency and latency variability of correct saccades were analyzed. Dominant model analysis was carried out to compare participants with homozygous major alleles genotypes and minor allele carriers in patient and control groups independently. Genotype x Diagnosis interaction was significant for rs6277 and rs2242592 in relation to error rate: healthy minor alleles (possibly associated with risk of schizophrenia) carriers committed significantly fewer errors compared to dominant homozygotes individuals, minor alleles carriers in schizophrenia group had increased error rate. In both groups the carriers of minor alleles performed AS with shorter latencies and decreased latency variability, the significance of Genotype was revealed in the pooled samples for rs6275 and rs6277.

conclusionsThe role of possible DRD2 genotype-related striatal changes in prefrontal cortex dysfunction in schizophrenia was suggested. A high level of DRD2 expression in striatum corresponding to minor alleles improved motor indices of saccades in both groups. The findings have implications for understanding the mechanisms of individual variability in executive functioning and response to antipsychotic medication in schizophrenia.