The involvement of functional polymorphism of COMT rs4680 gene in the pathogenesis of cognitive impairment in schizophrenia

Introduction. Cognitive dysfunction in schizophrenia and schizophrenic spectrum disorders critically reduce the patient's social functioning. Unlike productive symptoms, cognitive dysfunction is very persistent and difficult to correct. The role of genetics in the development of cognitive deficits in schizophrenia has been the subject of research for several decades. However, many aspects of the contribution of genetics to cognitive function are still not systematised. One of the most studied in schizophrenia is the rs4680 polymorphism of the COMT (Catechol-O-MethylTransferase) gene, which encodes an enzyme that regulates the breakdown of catecholamines (dopamine, adrenaline, noradrenaline, etc.). The GA single nucleotide substitution results in methionine instead of valine. The A (Met) allele is associated with lower enzymatic activity of COMT due to its thermal instability.Objective. To evaluate associations of COMT polymorphism with cognitive function in schizophrenia.Methods. In this study, a systematic literature search was conducted on 4 databases: PubMed, Cochrane, E-library, and Google Scholar for the last 10 years. The association of rs4680 with cognitive impairment was analysed in 11 studies.Results. Patients with the Met allele performed better on selected measures of cognitive assessment scales in most studies.Conclusion. If these findings are confirmed in large samples, the rs4680 polymorphism in the COMT gene in patients with schizophrenia will allow specialists to choose a more optimal therapeutic strategy in the early stages of the disease, which will improve the quality of life of patients, their labour and social prognosis.