Płaza Olga, Gałecki Piotr, Orzechowska Agata, Gałecka Małgorzata, Sobolewska-Nowak Justyna, Szulc Agata
Department of Psychiatry, Faculty of Health Sciences, Medical University of Warsaw, Partyzantów 2/4, 05-800 Pruszków, Poland.
Department of Adult Psychiatry, Medical University of Łódź, Aleksandrowska 159, 91-229 Łódź, Poland.
Biomedicines. 2022 Dec 7;10(12):3165. doi: 10.3390/biomedicines10123165.
Schizophrenia (SCZ) is a complex psychiatric disorder of multifactorial origin, in which both genetic and environmental factors have an impact on its onset, course, and outcome. Large variability in response and tolerability of medication among individuals makes it difficult to predict the efficacy of a chosen therapeutic method and create universal and precise guidelines for treatment. Pharmacogenetic research allows for the identification of genetic polymorphisms associated with response to a chosen antipsychotic, thus allowing for a more effective and personal approach to treatment. This review focuses on three frequently prescribed second-generation antipsychotics (SGAs), risperidone, olanzapine, and aripiprazole, and aims to analyze the current state and future perspectives in research dedicated to identifying genetic factors associated with antipsychotic response. Multiple alleles of genes involved in pharmacokinetics (particularly isoenzymes of cytochrome P450), as well as variants of genes involved in dopamine, serotonin, and glutamate neurotransmission, have already been identified as ones of significant impact on antipsychotic response. It must, however, be noted that although currently obtained results are promising, trials with bigger study groups and unified protocols are crucial for standardizing methods and determining objective antipsychotic response status.
精神分裂症(SCZ)是一种起源于多因素的复杂精神疾病,其中遗传和环境因素都会对其发病、病程及预后产生影响。个体间药物反应和耐受性差异很大,这使得预测所选治疗方法的疗效并制定通用且精确的治疗指南变得困难。药物遗传学研究能够识别与所选抗精神病药物反应相关的基因多态性,从而实现更有效且个性化的治疗方法。本综述聚焦于三种常用的第二代抗精神病药物(SGA),即利培酮、奥氮平和阿立哌唑,旨在分析致力于识别与抗精神病药物反应相关遗传因素的研究现状及未来前景。参与药代动力学的基因(尤其是细胞色素P450同工酶)的多个等位基因,以及参与多巴胺、5-羟色胺和谷氨酸神经传递的基因变体,已被确定为对抗精神病药物反应有重大影响的因素。然而,必须指出的是,尽管目前取得的结果很有前景,但采用更大样本量研究组和统一方案的试验对于规范方法及确定客观的抗精神病药物反应状态至关重要。