Influence of single nucleotide polymorphisms of the serotonergic system genes on the occurrence of therapeutic resistance manifestations in patients with schizophrenia

Introduction. In recent years, the problem of treatment-resistant schizophrenia has been actively studied, but the etiology of this condition is not fully clear. One of the concepts of the pathogenesis of schizophrenia is a genetic theory, in particular, studying the influence of the carriage of single nucleotide polymorphisms (SNPs) of the serotonergic system genes. Objective: to determine the association and frequency of carriage of the SNP gene HTR2A rs7997012 (g.64185T>G, g.64185T>C, g.64185T>A) and rs6313 (g.6230C>T, g.6230C>G) with risk of development of therapeutically resistant schizophrenia during antipsychotic therapy. Materials and Methods. A prospective study was performed based on the Department of Biological Therapy of Mentally Ill of Federal State Budgetary Institution “V.M. Bekhterev National Medical Research Center for Psychiatry and Neurology” of the Ministry of Health of Russia. The study sample included 103 patients with paranoid schizophrenia (F20.0 according to ICD-10) aged 18-50 years, including 53 women and 50 men. All patients were examined using the Positive and Negative Syndrome Scale (PANSS) at two points: by day 1 and day 56 of the study. Also, all patients underwent genetic testing to determine the carriage of the HTR2A gene under study. Depending on the response to therapy, groups of responders and nonresponders were identified. Results. According to the findings of the study, it was determined that the dependent variable is dichotomous, and the independent variables are characterized as categorical. The final model included one significant variable - carriage of the heterozygous genotype CT SNP rs6313 (g.6230C>T) of the HTR2A gene. Conclusion. Determination of the genetic predisposition of patients with schizophrenia reveals the mechanisms for the development of therapeutically resistant schizophrenia, and also provides an opportunity to select effective therapy.