Wayne State University Eugene Applebaum College of Pharmacy and Health Sciences, Detroit, Michigan.
Wayne State University School of Medicine, Detroit, Michigan.
Pharmacotherapy. 2020 Apr;40(4):331-342. doi: 10.1002/phar.2375. Epub 2020 Mar 9.
The pharmacoepigenetics of antipsychotic treatment in severe mental illness is a growing area of research that aims to understand the interface between antipsychotic treatment and genetic regulation. Pharmacoepigenetics may some day assist in identifying treatment response mechanisms or become one of the components in the implementation of precision medicine. To understand the current evidence regarding the effects of antipsychotics on DNA methylation a systematic review with qualitative synthesis was performed through Pubmed, Embase and Psychinfo from earliest data to June 2019. Studies were included if they analyzed DNA methylation in an antipsychotic-treated population of patients with schizophrenia or bipolar disorder. Data extraction occurred via a standardized format and study quality was assessed. Twenty-nine studies were identified for inclusion. Study design, antipsychotic type, sample source, and methods of DNA methylation measurement varied across all studies. Eighteen studies analyzed methylation in patients with schizophrenia, four studies in patients with bipolar disorder, and seven studies in a combined sample of schizophrenia and bipolar disorder. Twenty-two studies used observational samples whereas the remainder used prospectively treated samples. Six studies assessed global methylation, five assessed epigenome-wide, and 15 performed a candidate epigenetic study. Two studies analyzed both global and gene-specific methylation, whereas one study performed a simultaneous epigenome-wide and gene-specific study. Only three genes were analyzed in more than one gene-specific study and the findings were discordant. The state of the pharmacoepigenetic literature on antipsychotic use is still in its early stages and uniform reporting of methylation site information is needed. Future work should concentrate on using prospective sampling with appropriate control groups and begin to replicate many of the novel associations that have been reported.
抗精神病药物治疗严重精神疾病的药物基因组学是一个不断发展的研究领域，旨在了解抗精神病药物治疗与基因调控之间的关系。药物基因组学可能有助于识别治疗反应机制，或成为精准医学实施的组成部分之一。为了了解抗精神病药物对 DNA 甲基化影响的现有证据，我们通过 Pubmed、Embase 和 Psychinfo 进行了系统评价，检索了最早至 2019 年 6 月的数据。如果研究分析了精神分裂症或双相情感障碍患者的抗精神病药物治疗人群中的 DNA 甲基化，则将其纳入研究。通过标准化格式进行数据提取，并评估研究质量。确定了 29 项研究纳入本研究。所有研究的研究设计、抗精神病药物类型、样本来源和 DNA 甲基化测量方法均有所不同。18 项研究分析了精神分裂症患者的甲基化，4 项研究分析了双相情感障碍患者的甲基化，7 项研究分析了精神分裂症和双相情感障碍的混合样本。22 项研究使用了观察性样本，其余研究则使用了前瞻性治疗样本。6 项研究评估了全基因组甲基化，5 项研究评估了全基因组范围，15 项研究进行了候选性表观遗传学研究。有两项研究分析了全基因组和基因特异性甲基化，一项研究同时进行了全基因组范围和基因特异性研究。只有三项基因在一项以上的基因特异性研究中被分析，并且研究结果存在差异。抗精神病药物使用的药物基因组学文献状况仍处于早期阶段，需要统一报告甲基化位点信息。未来的工作应集中在使用前瞻性采样和适当的对照组，并开始复制已报道的许多新的关联。
