The longitudinal associations of inflammatory biomarkers and depression revisited: systematic review, meta-analysis, and meta-regression.
Level 3 - non-randomized controlled study
Systematic review and meta-analysis of prospective cohort studies
PubMed 32807846 · doi:10.1038/s41380-020-00867-4
What was done
The authors conducted a PROSPERO-registered systematic review and random-effects meta-analysis of prospective cohort studies examining bidirectional associations between depressive symptoms and inflammatory biomarkers (IL-6, TNF-alpha, and CRP) in community samples. Literature searches were conducted through January 2019 across MEDLINE, PsycINFO, PsycARTICLES, EMBASE, and Proquest Dissertations. Standardized Fisher transformations of correlation and beta coefficients were extracted for unadjusted and covariate-adjusted models, with meta-regression applied to evaluate moderators.
What was found
From 38 included studies representing 58,256 participants (up to 27 studies in the meta-analysis), higher baseline CRP and IL-6 were prospectively associated with higher future depressive symptoms, and baseline depressive symptoms were prospectively associated with higher future CRP and IL-6 in both unadjusted and adjusted models. The adjusted prospective associations between CRP and depression were substantially attenuated and small in magnitude (no specific effect sizes or confidence intervals were reported in the abstract). No significant prospective associations were found for TNF-alpha, and findings were inconclusive for clinical depression. Meta-regression showed the CRP-depression association was larger in older cohorts and in studies failing to control for infection.
Why it matters
This review demonstrates that peripheral inflammatory markers (particularly IL-6 and CRP) have small, bidirectional longitudinal associations with depressive symptoms, but substantial covariate attenuation suggests inflammation alone accounts for a modest share of depression risk.
Limits
The abstract reports no numerical effect sizes or confidence intervals. Evidence is limited to depressive symptoms in community samples rather than clinical major depressive disorder, and findings were complicated by substantial heterogeneity across studies and lack of infection control in some cohorts.
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