Effects of exercise training on inflammatory, neurotrophic and immunological markers and neurotransmitters in people with depression: A systematic review and meta-analysis

Major depressive disorder is the most common type of mental disorder. The biological pathway by which exercise promotes its antidepressant effects remains uncleared. This study aimed to systematically review the chronic effect of exercise on blood biomarkers and its association with changes in depressive symptoms in adults with major depressive disorder. Randomized controlled trials (RCT) published until February 2020 were screened in seven databases. Studies were systematically reviewed by two independent reviewers. Random effect meta-analysis was performed and reported as standardized mean differences (SMD) and 95 % confidence interval (CI). The meta- analysis protocol was registered with PROSPERO (CRD42021221177). From 3865 records, 12 studies (N = 757 participants, mean age [SD]: 43.0 [11.0], 66.2 % women) were included in this review. Exercise training resulted in superior increase in circulating BDNF (SMD: 0.44, 95%CI: 0.15, 0.73) and kynurenine (SMD: 0.29, 95%CI: 0.04, 0.54), and decrease depressive symptoms (SMD: −0.72, 95%CI: −1.08, −0.37) in adults with major depression disorder compared to control groups. Multivariate meta-regression analysis showed that improvements in circulating levels of BDNF, kynurenine and interleukyn-6 were associated with decreases in depressive symptoms. Results were not stratified by the type of medication used by participants due to the lack of reporting of the included studies. Few studies provided data on other biomarkers (e.g., TNF-α and IL-10) besides BNDF and kynurenine. Antidepressant effect of exercise may be triggered by improved circulating levels of BNDF, kynurenine, and interleukine-6 in adults with major depressive disorder.