Impact of COMT, PRODH and DISC1 Genetic Variants on Cognitive Performance of Patients with Schizophrenia

Abstract

Background: Cognitive impairment in schizophrenia (SCZ) is a core feature, relevant for the disease prognosis and functional capacity of the patients. It has also been identified as an endophenotype and proposed as a genetic mechanism of risk for schizophrenia.

Aim of the study: We aimed to evaluate the association of genetic variants in COMT, PRODH, and DISC1 with the cognitive performance of Mexican-Mestizo adult patients with SCZ in order to identify endophenotypes.

Subjects and methods: The association of seven variants in COMT, 15 in PRODH, and three in DISC1 was evaluated in 150 patients and 150 control volunteers. The MATRICS Consensus Cognitive Battery was administered to a subset of 44 patients and 42 controls.

Results: COMT rs4633 was related to MATRICS global assessment, while in the multi-phenotype analysis, PRODH rs2870984 was associated with processing speed, working memory, verbal learning, and social cognition. In addition, the association of variants in COMT and PRODH with the risk for SCZ was also found in Mexican-Mestizo patients.

Conclusion: COMT might be a potential biomarker of cognitive impairment in Mexican-Mestizo patients with SCZ, supporting the relevance of this gene for drug design.

Keywords: Catechol-O-methyltransferase; Cognition; Disrupted in schizophrenia 1 protein; Genetic variants; Proline dehydrogenase; Schizophrenia spectrum disorders.