The associations between DNA methylation and depression: A systematic review and meta-analysis.

Background: Growing evidence suggests that epigenetic modification is vital in biological processes of depression. Findings from studies exploring the associations between DNA methylation and depression have been inconsistent.

Methods: A systematical search of EMBASE, PubMed, Web of Science, and PsycINFO databases was conducted to include studies focusing on the associations between DNA methylation and depression (up to November 1st 2021) according to PRISMA guidelines with registration in PROSPERO (CRD42021288664).

Results: A total of 47 studies met inclusion criteria and 31 studies were included in the meta-analysis. This meta-analysis found that genes hypermethylation, including BDNF (OR: 1.15, 95%CI: 1.01-1.32, I = 90 %), and NR3C1 (OR: 1.43, 95%CI: 1.09-1.87, I = 88 %) was associated with increased risk of depression. Significant association of SLC6A4 hypermethylation with depression was only found in the subgroup of using original data (OR: 1.09, 95%CI: 1.01-1.19, I = 52 %). BDNF hypermethylation could increase the risk of depression only in the Asian population (OR: 1.18, 95%CI: 1.01-1.40, I = 91 %), and significant associations of NR3C1 hypermethylation with depression were found in the group for depressive symptoms (OR: 1.34, 95%CI: 1.08-1.67, I = 85 %), but not for depressive disorder (OR: 1.89, 95%CI: 0.54-6.55, I = 94 %).

Limitations: More studies are needed to explore the factors that might influence the estimates owing to the contextual heterogeneity of the pooling of included studies.

Conclusions: It is noted that DNA hypermethylation, namely BDNF and NR3C1, is associated with increased risk of depression. The findings in this study could provide some material evidence for preventing and diagnosing of depression.