The influence of prefrontal and striatal dopaminergic genes on cognitive control in high and low schizotypy

Background: Healthy individuals with schizotypal features exhibit subtle cognitive deficits that are similar, although less severe, to the cognitive deficits observed in schizophrenia. Converging evidence from pharmacological investigations, genetic studies and schizophrenia research indicates an important influence of prefrontal and striatal dopaminergic systems in areas of cognitive control. The association between schizotypy and cognitive performance was explored in a sample of healthy adults in relation to polymorphisms in the COMT gene (rs4680) and the dopamine D2 receptor (DRD2) gene (rs6277) that are associated with prefrontal and striatal dopaminergic functioning, respectively. Methods: 91 healthy volunteers were assessed for schizotypy using the Oxford- Liverpool Inventory of Feelings and a median split on the Unusual Experience scale created high and low schizotypy groups. Cognitive performance was assessed across working memory (letter-number-span) and inhibition (STROOP). Genotyping of the val(158)met polymorphism of the COMT gene (met/met, met/val, val/val) and the C957T polymorphism of the DRD2 gene (TT, C/T, CC) was performed. Results: ANOVAs revealed a significant interaction between DRD2 C957T variants and high/low schizotypy on working memory (p=.008), with the poorest performance observed in the high schizotypy / TT group. There were no interactions observed between COMT variants and schizotypy on cognition. Conclusions: This research has shown that the functional polymorphism C957T (rs6277) on the DRD2 gene, that has been found to predict striatal DRD2 binding potential, interacts with schizotypy and influences working memory. This finding extends previous research that has independently linked striatal dopamine availability to schizophrenia, schizotypal features in healthy volunteers, and cognitive control