Search for Association of Polymorphisms rs6280 of the DRD3 Gene, rs4680 of the COMT Gene, rs6265 of the Gene BDNF with Schizophrenia Resistant to Antipsychotic Therapy in Russian Populations

M. Kaydan, N. V. Zakharova, Y. Zorkina, G. Kostyuk
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Abstract

Background: resistant schizophrenia, despite the introduction of new antipsychotics and diagnostic methods, still reaches 50%of cases among all patients with schizophrenia. The search for new methods of early diagnosis using personalized genetic analysis tools seems relevant and promising at the present time. The aim of the study was to analyze the associations of polymorphisms COMT rs4680, DRD3 rs6280, BDNF rs6265 with the development of a therapeutic resistance in patients with schizophrenia. Patients and methods: а real-time genetic analysis of 264 patients with schizophrenia examined by clinical and psychometric methods. A prospective follow-up for 6 weeks was carried out with further division of the sample into 2 groups: respondents and patients with resistance based on the evaluation of the effectiveness of psychopharmacotherapy. Results: a significant association with the ineffectiveness of psychopharmacotherapy found in patients with schizophrenia being homozygotes in the recessive model and being heterozygotes in the codominant model of the rs6265 polymorphism of the BDNF gene. Conclusions: the rs6265 polymorphism of the BDNF gene can be considered as a diagnostic marker for the development of treatment resistant schizophrenia, but requires further study to confirm sensitivity and specificity.
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寻找俄罗斯人群中 DRD3 基因 rs6280、COMT 基因 rs4680 和 BDNF 基因 rs6265 多态性与抗精神病药物治疗耐受性精神分裂症的关系
背景:尽管引入了新的抗精神病药物和诊断方法,但在所有精神分裂症患者中,耐药性精神分裂症的病例仍高达 50%。目前,利用个性化基因分析工具寻找早期诊断的新方法似乎具有现实意义和前景。本研究旨在分析多态性 COMT rs4680、DRD3 rs6280、BDNF rs6265 与精神分裂症患者耐药性发展的关系。患者和方法:通过临床和心理测量方法对 264 名精神分裂症患者进行实时遗传分析。进行了为期 6 周的前瞻性随访,并根据对精神药物治疗效果的评估,将样本进一步分为两组:应答者和有抗药性的患者。结果:在 BDNF 基因 rs6265 多态性的隐性模型中发现,精神分裂症患者中的同型杂合子和共显性模型中的异型杂合子与精神药物治疗无效有明显关联。结论:BDNF基因的rs6265多态性可被视为耐药性精神分裂症的诊断标记,但需要进一步研究以确认其敏感性和特异性。
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