More than a third of patients treated with antidepressants experience treatment resistance. Furthermore, molecular pathways involved in antidepressant effect have yet to be fully understood. Therefore, we performed a systematic review of clinical studies that examined changes in RNA expression levels produced by antidepressant treatment. Literature search was performed through April 2021 for peer-reviewed studies measuring changes in mRNA or non-coding RNA levels before and after antidepressant treatment in human participants following PRISMA guidelines. Thirty-one studies were included in qualitative synthesis. We identified a large amount of heterogeneity between the studies for genes/RNAs measured, antidepressants used, and treatment duration. Of the six RNAs examined by more than one study, expression of the brain-derived neurotrophic factor (BDNF) gene and genes in the inflammation pathway, particularly IL-1β, were consistently reported to be altered by antidepressant treatment. Limitations of this review include heterogeneity of the studies, possibility of positive publication bias, and risk of false-negative findings secondary to small sample sizes. In conclusion, our systematic review provides an updated synthesis of RNA expression changes produced by antidepressant treatment in human participants, where genes in the BDNF and inflammatory pathways were identified as potential targets of antidepressant effect. Importantly, these findings also highlight the need for replication of the included studies in multiple strong, placebo-controlled studies for the identification of evidence-based markers that can be targeted to improve treatment outcomes.

接受抗抑郁药治疗的患者中，超过三分之一会出现耐药性。此外，参与抗抑郁作用的分子途径尚未完全了解。因此，我们对检查抗抑郁治疗产生的 RNA 表达水平变化的临床研究进行了系统回顾。文献检索一直持续到 2021 年 4 月，以获取同行评审的研究，这些研究测量了人类参与者在遵循 PRISMA 指南进行抗抑郁治疗前后 mRNA 或非编码 RNA 水平的变化。31 项研究被纳入定性综合。我们确定了在测量的基因/RNA、使用的抗抑郁药和治疗持续时间的研究之间存在大量异质性。在一项以上研究检查的六种 RNA 中，据报道，脑源性神经营养因子 (BDNF) 基因和炎症通路中的基因，特别是 IL-1β 的表达，一直被抗抑郁药治疗改变。本综述的局限性包括研究的异质性、阳性发表偏倚的可能性以及小样本导致的假阴性结果的风险。总之，我们的系统评价提供了人类参与者抗抑郁治疗产生的 RNA 表达变化的最新合成，其中 BDNF 和炎症通路中的基因被确定为抗抑郁作用的潜在靶点。重要的是，这些发现还强调需要在多个强有力的、