Mednova Irina A, Mikhalitskaya Ekaterina V, Vyalova Natalia M, Paderina Diana Z, Petkun Dmitry A, Tiguntsev Vladimir V, Kornetova Elena G, Bokhan Nikolay A, Ivanova Svetlana A
Mental Health Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk 634014, Russia.
Department of Psychiatry, Narcology and Psychotherapy, Siberian State Medical University, Tomsk 634050, Russia.
Pharmaceuticals (Basel). 2025 Jun 21;18(7):941. doi: 10.3390/ph18070941.
The life expectancy of patients with psychotic disorders is significantly shorter than that of the general population; antipsychotic-induced metabolic disorders play a significant role in reducing life expectancy. Both metabolic syndrome (MetS) and schizophrenia are multifactorial conditions. One area where the two conditions overlap is oxidative stress, which is present in both diseases. The glutathione-S-transferase (GST) system is a major line of defense against exogenous toxicants and oxidative damage to cells. The aim of our study was to perform an association analysis of gene polymorphisms with metabolic disorders in patients with schizophrenia treated with antipsychotic therapy. : A total of 639 white patients with schizophrenia (ICD-10) from Siberia (Russia) were included in the study. Genotyping was carried out using real-time polymerase chain reaction for two single-nucleotide polymorphisms (SNPs) in the (rs614080 and rs1695) and one SNP in the (rs49252). : We found that rs1695GG genotype of is a risk factor for the development of overweight (OR 2.36; 95% CI: 1.3-4.29; = 0.0054). In the subgroup of patients receiving first-generation antipsychotics as basic therapy, the risk of overweight was associated with carriage of the rs1695GG (OR 5.43; 95% CI: 2.24-13.16; < 0.001) genotype of in a recessive model of inheritance. In contrast, an association of rs1695*G GSTP1 with obesity (OR: 0.42; 95% CI: 0.20-0.87; = 0.018) was shown in the dominant model of inheritance in patients receiving second-generation antipsychotics. : The pilot results obtained confirm the hypothesis of a violation of the antioxidant status, in particular the involvement of in the development of antipsychotic-induced metabolic disorders in schizophrenia. Further studies with larger samples and different ethnic groups are needed to confirm the obtained results.
精神障碍患者的预期寿命显著短于普通人群；抗精神病药物所致的代谢紊乱在缩短预期寿命方面起重要作用。代谢综合征（MetS）和精神分裂症均为多因素疾病。这两种疾病重叠的一个领域是氧化应激，两种疾病中均存在氧化应激。谷胱甘肽 - S - 转移酶（GST）系统是抵御外源性毒物和细胞氧化损伤的主要防线。我们研究的目的是对接受抗精神病治疗的精神分裂症患者的基因多态性与代谢紊乱进行关联分析。：本研究纳入了来自俄罗斯西伯利亚的639例白人精神分裂症患者（ICD - 10）。使用实时聚合酶链反应对谷胱甘肽 - S - 转移酶P1（GSTP1）基因的两个单核苷酸多态性（SNP）（rs614080和rs1695）以及谷胱甘肽 - S - 转移酶M1（GSTM1）基因的一个SNP（rs49252）进行基因分型。：我们发现GSTP1基因rs1695GG基因型是超重发生的危险因素（比值比[OR] 2.36；95%置信区间[CI]：1.3 - 4.29；P = 0.0054）。在以第一代抗精神病药物作为基础治疗的患者亚组中，超重风险与GSTP1基因rs1695GG基因型（OR 5.43；95% CI：2.24 - 13.16；P < 0.001）的隐性遗传模式相关。相反，在接受第二代抗精神病药物治疗的患者中，显性遗传模式下显示rs1695*G GSTP1与肥胖相关（OR：0.42；95% CI：0.20 - 0.87；P = 0.018）。：所获得的初步结果证实了抗氧化状态受损的假设，特别是GSTP1参与精神分裂症中抗精神病药物所致代谢紊乱的发生。需要进一步开展更大样本量和不同种族群体的研究以证实所获结果。
