Osimo · Brain, behavior, and immunity 2020 · systematic review and meta-analysis of case-control studies · n=107 studies (5,166 patients, 5,083 controls)

Inflammatory markers in depression: A meta-analysis of mean differences and variability in 5,166 patients and 5,083 controls.

Cited 932 times in the scientific literature.

Level 4 - case-series / case-control

Meta-analysis of observational case-control studies

PubMed 32113908 · doi:10.1016/j.bbi.2020.02.010 · record verified 2026-08-30

What was done

Systematic review and multivariate meta-analysis of case-control studies indexed in MEDLINE up to August 29, 2018. The study evaluated mean differences (Hedges' g) and relative variability (coefficient of variation ratio, CVR) of peripheral blood immune markers between patients with depression and matched healthy controls across 107 studies comprising 5,166 patients and 5,083 controls.

What was found

Peripheral blood levels of several inflammatory markers were significantly higher in patients with depression: - CRP: g = 0.71 (95% CI: 0.50–0.92; p < 0.0001) - IL-3: g = 0.60 (95% CI: 0.31–0.89; p < 0.0001) - IL-6: g = 0.61 (95% CI: 0.39–0.82; p < 0.0001) - IL-12: g = 1.18 (95% CI: 0.74–1.62; p < 0.0001) - IL-18: g = 1.97 (95% CI: 1.00–2.95; p < 0.0001) - sIL-2R: g = 0.71 (95% CI: 0.44–0.98; p < 0.0001) - TNFα: g = 0.54 (95% CI: 0.32–0.76; p < 0.0001) Relative variability (CVR) was significantly lower in patients with depression for CRP (CVR = 0.85; 95% CI: 0.75–0.98; p = 0.02), IL-12 (CVR = 0.61; 95% CI: 0.46–0.80; p < 0.01), and sIL-2R (CVR = 0.85; 95% CI: 0.73–0.99; p = 0.04), while unchanged for IL-3, IL-6, IL-18, and TNFα.

Why it matters

Elevated inflammatory markers accompanied by equal or reduced variability suggest that systemic inflammation in depression reflects a general rightward shift in the immune profile rather than a phenomenon limited to a distinct inflamed subgroup.

Limits

All included data derive from observational case-control designs, precluding causal inference. Peripheral blood measures may not reflect central neuroinflammation. Potential residual confounding from somatic health, medication, or lifestyle factors cannot be fully excluded based on abstract data alone.

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