Exercise as a complementary therapy for depression: a systematic review and meta-analysis of randomized controlled trials and bioinformatics exploration gene network model .

Background The effect of pharmacological treatment (PT), exercise treatment (ET), and both in depressive symptoms remains a matter of debate. The present study aimed to clarify (1) the effect of ET as a monotherapy or complementary treatment of pharmacological therapy; (2) changes in the dose-response for different exercise prescription characteristics; and 3) hypothesizing about the gene network model of exercise effects on depression. Methods We sought Randomized Controlled Trials (RCT) addressing the effects of exercise on depressive patients, published in peer-reviewed journals between 2003-2019 in Scopus, Cochrane, Pubmed/Medline, ISI Web of Knowledge and APA PsycNET databases. Standardized mean difference (SMD) was calculated considering the mean difference on depression scales (pre and post-intervention) and pooled standard deviation for each intention-to-treat in each study. For the gene network model of exercise on depression an in silico analyses were used. Results We found 1,165 articles and selected 15 studies to this meta-analysis. RCTs with different ET and PT prescriptions were examined using the delta (pre and post-intervention) of a validated depression scale compared to the control group in different treatment conditions. Standardized mean differences and confidence intervals (SMD, 95% CI) were found for ET with or without PT group (-0.45, -0.62 to -0.29), ET and PT group (-0.70, -1.00 to -0.40), and only ET group (-0.39, -0.57 to -0.21). The subgroup analyses showed a moderate and large SMD in  favour of  resistance training (-0.67, -1.22 to -0.12), aerobic exercise 60-80% of maximum heart rate intensity (-0.56, -0.89 to -0.23), 20 to 30 minutes (-0.59, -0.88 to -0.31) or 45 to 60 minutes (-0.55, -0.81 to -0.29) duration per session, and seven times per week (-0.75, -1.30 to -0.20). Conclusion ET plus PT showed a better effect on reducing depressive symptoms, and the exercise prescription that shows the best dose-response in subgroup analyses can be the target for ET in depression. Also, the genes network model can withstand the effect of exercise in the depressive symptoms decrease according to an interaction between BDNF and inflammation. More well-designed studies are needed to confirm our findings.