GENETIC VARIANTS IN ANTIPSYCHOTIC METABOLISM: POLYMORPHISM PROFILES IN KAZAKH COHORT WITH PARANOID SCHIZOPHRENIA.

Abstract

Schizophrenia is a multifaceted psychiatric disorder characterized by hallucinations, delusions, cognitive impairments, and behavioral disturbances. Genetic factors significantly contribute to its pathogenesis, accounting for approximately 80% of the heritability. Globally, about 1% of the population is affected by schizophrenia, with 45,054 individuals in Kazakhstan receiving medical treatment for the condition, indicating a prevalence rate of 238,6 per 100,000 people. The rise in mental health disorders in Kazakhstan underscores the need for personalized treatment approaches to address these public health challenges. This study examines the influence of key polymorphisms - CYP2D6 (rs1135840), CYP3A5 (rs776746), COMT (rs4818, rs4680, rs9606186), CNR1 (rs1049353), HTR2A (rs6311, rs6313), and DRD2 (rs1799978, rs1800497) - on AP drug metabolism and therapeutic outcomes. The findings underscore the potential for genotype-guided AP dosage individualization in Kazakh individuals, laying a foundation for future research on optimizing AP therapy in this population.