Peripheral cytokine and chemokine alterations in depression: a meta‐analysis of 82 studies

Objective To conduct a systematic review and meta‐analysis of studies that measured cytokine and chemokine levels in individuals with major depressive disorder ( MDD ) compared to healthy controls ( HC s). Method The PubMed/MEDLINE, EMBASE , and PsycINFO databases were searched up until May 30, 2016. Effect sizes were estimated with random‐effects models. Result Eighty‐two studies comprising 3212 participants with MDD and 2798 HC s met inclusion criteria. Peripheral levels of interleukin‐6 ( IL ‐6), tumor necrosis factor ( TNF )‐alpha, IL ‐10, the soluble IL ‐2 receptor, C‐C chemokine ligand 2, IL ‐13, IL ‐18, IL ‐12, the IL ‐1 receptor antagonist, and the soluble TNF receptor 2 were elevated in patients with MDD compared to HC s, whereas interferon‐gamma levels were lower in MDD (Hedge's g = −0.477, P = 0.043). Levels of IL ‐1β, IL ‐2, IL ‐4, IL ‐8, the soluble IL ‐6 receptor ( sIL ‐6R), IL ‐5, CCL ‐3, IL ‐17, and transforming growth factor‐beta 1 were not significantly altered in individuals with MDD compared to HC s. Heterogeneity was large ( I 2 : 51.6–97.7%), and sources of heterogeneity were explored (e.g., age, smoking status, and body mass index). Conclusion Our results further characterize a cytokine/chemokine profile associated with MDD . Future studies are warranted to further elucidate sources of heterogeneity, as well as biosignature cytokines secreted by other immune cells.