Changes in RNA expression levels during antidepressant treatment: a systematic review

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.