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53. A systematic review and meta-analysis investigating the directionality of the prospective relationship between depression and inflammation in community and clinically depressed samples.
When an inflammatory response is induced, depressive symptoms reliably follow and inflammatory biomarkers [C-Reactive Protein(CRP); Interleukin-6(IL-6)] are consistently elevated in clinical depression. However, the role played by inflammation in the etiology of depression is unclear - does inflammation play a causal role or is it a by-product of shared risk factors (e.g., BMI, sedentary behavior)? A systematic review and meta-analysis was registered at PROSPERO that investigated the directionality of the relationship between CRP/IL-6 and depression in both community and clinically depressed samples, estimating effect sizes both adjusted for covariates and unadjusted. From 9989 potential papers, 48 were included in the systematic review, 18 of which were included in a meta-analysis. Systematic review highlighted significant, small bidirectional associations of depression and CRP/IL-6 that are substantially attenuated when important confounds are included in models, although conclusions are limited by profound methodological differences observed. Random-effects meta-analysis of 39,531 participants found small bidirectional associations between CRP/IL-6 and depression. When controlling for confounds, CRP/IL-6 predicted more severe future depression, but depression did not predict future CRP/IL-6. Meta-regression indicated that effect sizes were stronger in females and at shorter follow-up. Inflammatory biomarkers predict future depression when controlling for covariates, but not the reverse.