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The results of human studies are inconsistent regarding selenium and depressive disorders. Therefore, we aimed to conduct a systematic review and meta-analysis of observational and interventional studies and provided an overview of the role of selenium in depression. Three databases including Medline, Scopus, and Web of Science were searched on June 30, 2020 and updated on April 12, 2021. Also, we searched in electronical databases of WHO Global Index Medicus and ClinicalTrials.gov. No time or language restrictions were used for the search. A random effects model was used to pool effect sizes. In total, 20 studies were included in the systematic review, and 15 studies were included in the meta-analysis. There were no significant differences in serum selenium levels between patients with depression and healthy subjects (WMD: 2.12 mg/L; 95% CI: − 0.11, 4.36;  I  2  = 98.0%,  P  &lt; 0.001). Also, no significant correlation was found between serum levels of selenium and depression scores (r: − 0.12; 95% CI: − 0.33, 0.08;  I  2  = 73.5%,  P  = 0.010). Nevertheless, there was a significant negative association between high selenium intake and the risk of postpartum depression (OR: 0.97; 95% CI: 0.95, 0.99;  I  2  = 0.0%,  P  = 0.507). In addition, selenium supplementation significantly reduced depressive symptoms (WMD: − 0.37; 95% CI: − 0.56, − 0.18;  I  2  = 0.0%,  P  = 0.959). Taken these results together, selenium seems to have a protective role against postpartum depression and can be considered as a beneficial adjuvant therapy in patients with depression. Further studies are necessary to draw definitive conclusions.

The role of selenium in depression: a systematic review and meta-analysis of human observational and interventional studies