Evaluation of inflammatory cytokines in drug-naïve major depressive disorder: A systematic review and meta-analysis.

Objective

Altered levels of peripheral inflammatory and proinflammatory cytokine markers affect the different clinical stages of major depressive disorder (MDD). A concrete understanding of the causal mechanism of MDD is a prerequisite in developing treatment strategies and preventive plans. Here we aimed to conduct an updated systematic review and meta-analysis of studies assessing the association of C-reactive protein (CRP), INF-γ, MCP-1, and TNF-α in the peripheral fluid of drug-naïve MDD patients and healthy controls (HCs).

Methods

We extracted articles from PubMed, ProQuest, PsycINFO, Web of Science, and Scopus databases from inception until 14 February 2021, to find relevant studies. In this meta-analysis, we included a total of 23 eligible studies (1,366 MDD patients and 1,342 controls) in the final meta-analysis. The Cochran's chi-square Q-test and I2-index were applied to measure the heterogeneity and inconsistency of all combined results. We selected a random-effect model during the analysis and measured publication biases using the funnel plot. We performed Bonferroni adjustment for multiple testing.

Results

We found a high level of TNF-α in MDD patients than in control subjects Standardized Mean Difference (SMD) with a random-effects model: 1.04, 95% CI: 0.69-1.39, z = 5.84, p < 0.001). The levels of CRP (SMD with a random-effects model: 0.18, 95% CI: -0.85-1.23, z = 0.35, p = 0.73), INF-ɤ (SMD with a random-effects model: -0.05, 95% CI: -2.72-2.62, z = 0.03, p = 0.97), and MCP-1 (SMD with a random-effects model: 0.70, 95% CI: -0.09-1.49, z = 1.73, p = 0.08) were not significantly varies between MDD patients and HCs.

Conclusion

The present study findings suggest the upregulated level of peripheral TNF-α but not CRP, INF-γ, and MCP-1 involve in depression. The elevated inflammatory cytokines confirmed the inflammatory state of depression. Therefore, inflammatory cytokines might serve as potential risk assessment markers in MDD.