The influence of the COMT genotype in the underlying functional brain activity of context processing in schizophrenia and in relatives

• Schizophrenia spectrum patients and their relatives have context processing deficits and show hyperactivation of medial frontal areas during context processing.
• The Val158Met COMT polymorphism influences on context processing and on its underlying brain activation.
• The COMT genotype with less dopamine availability in PFC (Val/Val) is associated with worse context processing performance and less PFC recruitment.

Context processing deficits have been shown to be present in chronic and first episode schizophrenia patients and in their relatives. This cognitive process is linked to frontal functioning and is highly dependent on dopamine levels in the prefrontal cortex (PFC). The catechol-O-methyltransferase (COMT) enzyme plays a prominent role in regulating dopamine levels in PFC. Genotypic variations in the functional polymorphism Val158Met COMT appear to have an impact in dopamine signaling in the PFC of healthy subjects and schizophrenia patients. We aimed to explore the effect of the Val158Met COMT polymorphism on brain activation during the performance of a context processing task in healthy subjects, schizophrenia spectrum patients and their healthy relatives. Methods: 56 participants performed the Dot Probe Expectancy task (DPX) during the fMRI session. Subjects were genotyped and only the Val and Met homozygotes participated in the study. Results: Schizophrenia spectrum patients and their relatives showed worse performance on context processing measures than healthy control subjects. The Val allele was associated with more context processing errors in healthy controls and in relatives compared to patients. There was a greater recruitment of frontal areas (supplementary motor area/cingulate gyrus) during context processing in patients relative to healthy controls. Met homozygotes subjects activated more frontal areas than Val homozygotes subjects. Conclusions: The Val158Met COMT polymorphism influences context processing and on its underlying brain activation, showing less recruitment of frontal areas in the subjects with the genotype associated to lower dopamine availability in PFC.