The role of gene polymorphism of the dopamine andglutamate systems in the clinical heterogeneity of schizophrenia and the development of antipsychotic-induced sideeffects

Objective: to search for genetic markers of the risk of development and adverse course of schizophrenia, as well as side effects of antipsychotic therapy to improve early diagnosis and personalized approaches to the treatment of this group of patients. Materials and Methods. A comprehensive clinical and biological examination was performed on the basis ofMental Health Research Institute of Tomsk National Research Medical Center, Tomsk Regional Clinical Psychiatric Hospital, and Kemerovo Regional Psychiatric Hospital. Status of patients (n=850) who underwent inpatient treatment in 2012-2022, at the time of the examination, met the diagnostic criteria for schizophrenia (F20) according to ICD-10. Psychopathological symptoms were assessed using the Positive and Negative Syndromes Scale (PANSS) and a modified version of the standardized description card for a patient with schizophrenia. The severity of adverse movement disorders during pharmacotherapy was assessed using the AIMS scale. The concentration of prolactin in the blood serum was determined by enzyme immunoassay. Discussion. The article presents the results of our own research in the field of genetics of clinical heterogeneity of schizophrenia and pharmacogenetics of antipsychotic-induced side effects in the paradigm of dysregulation of the dopamine and glutamate neurotransmitter systems. Associations of polymorphic variants of the genes of the dopamine and glutamate systems with unfavorable clinical phenotypes of schizophrenia, namely, with an early age of onset of the disease, a continuous type of course and leading negative symptoms, as well as with concomitant behavioral patterns (alcohol abuse and tobacco dependence), were revealed. Associations of polymorphic variants of genes of dopamine and glutamate systems with the risk of developing tardive dyskinesia, hyperprolactinemia and metabolic syndrome in patients with schizophrenia receiving long-term antipsychotic therapy are shown. The obtained fundamental data can serve as a basis for the development of new medical technologies.