The impact of the Val158Met COMT polymorphism on context processing in patients on the schizophrenia spectrum and their relatives

Introduction: The level of dopamine in the prefrontal cortex (PFC) appears to play a fundamental role in cognitive alterations in schizophrenia. The Val158Met polymorphism of the catechol-O-methyltransferase (COMT) enzyme impacts dopamine availability in the prefrontal cortex and can thus influence cognitive functioning. Among the different cognitive deficits found in schizophrenia patients, context processing deficits have been noted as a specific characteristic of schizophrenia, for which the cerebral substrate appears to be located in the dorsolateral PFC. In this study, we examine the impact of the Val158Met COMT polymorphism on context processing in a sample of patients on the schizophrenia spectrum, their relatives, and healthy control subjects evaluated using the Dot Probe Expectancy Task (DPX). Methods: Forty patients on the schizophrenia spectrum, 26 relatives, and 63 healthy control subjects were genotyped and performed the DPX test. Results: Both patients and their relatives demonstrated deficits in context processing influenced by the Val158Met COMT polymorphism. Compared with the other subjects, the Val/Val subjects showed poorer performance on context processing tasks. Conclusions: Deficits in context processing in schizophrenic patients and their families are influenced by the Val158Met COMT functional polymorphism, likely as a consequence of reduced dopamine availability in the PFC