Prediction of treatment response to antipsychotic drugs for precision medicine approach to schizophrenia: randomized trials and multiomics analysis

作者：Liangkun Guo, Yi Su, Yuyanan Zhang, Hao Yu, Zhe Lu, Wenqiang Li, Yongfeng Yang, Xiao Xiao, Hao Yan, Tianlan Lu, Jun Li, Yundan Liao, Zhewei Kang, Lifang Wang, Yue Li, Ming Li, Bing Liu, Hailiang Huang, Luxian Lv, Yin Yao, Yunlong Tan, Gerome Breen, Ian Everall, Hongxing Wang, Zhuo Huang, Dai Zhang, Weihua Yue · 发表于：Military Medical Research · 年份：2023 · DOI：10.1186/s40779-023-00459-7 · 被引用次数：40 · 研究领域：Schizophrenia research and treatment、Genetic Associations and Epidemiology、Tryptophan and brain disorders

Abstract Background Choosing the appropriate antipsychotic drug (APD) treatment for patients with schizophrenia (SCZ) can be challenging, as the treatment response to APD is highly variable and difficult to predict due to the lack of effective biomarkers. Previous studies have indicated the association between treatment response and genetic and epigenetic factors, but no effective biomarkers have been identified. Hence, further research is imperative to enhance precision medicine in SCZ treatment. Methods Participants with SCZ were recruited from two randomized trials. The discovery cohort was recruited from the CAPOC trial ( n = 2307) involved 6 weeks of treatment and equally randomized the participants to the Olanzapine, Risperidone, Quetiapine, Aripiprazole, Ziprasidone, and Haloperidol/Perphenazine (subsequently equally assigned to one or the other) groups. The external validation cohort was recruited from the CAPEC trial ( n = 1379), which involved 8 weeks of treatment and equally randomized the participants to the Olanzapine, Risperidone, and Aripiprazole groups. Additionally, healthy controls ( n = 275) from the local community were utilized as a genetic/epigenetic reference. The genetic and epigenetic (DNA methylation) risks of SCZ were assessed using the polygenic risk score (PRS) and polymethylation score, respectively. The study also examined the genetic-epigenetic interactions with treatment response through differential methylation analysis, methylation quantitat...