Valkanova · Journal of affective disorders 2013 · systematic review and meta-analysis of longitudinal studies · n=11 studies

CRP, IL-6 and depression: a systematic review and meta-analysis of longitudinal studies.

Cited 969 times in the scientific literature.

Level 3 - non-randomized controlled study

Systematic review and meta-analysis of non-randomized longitudinal cohort studies

PubMed 23870425 · doi:10.1016/j.jad.2013.06.004 · record verified 2026-08-29

What was done

The authors conducted a systematic review and meta-analysis across three databases (1970–2012) evaluating longitudinal studies with repeat data on baseline CRP or IL-6 levels and subsequent depressive symptoms. Effect sizes were pooled using mixed-effects models, with stratified analyses for specific inflammatory markers and age groups.

What was found

Eight studies evaluated CRP (14,832 participants) and three evaluated IL-6 (3,695 participants). Increased CRP significantly predicted subsequent depressive symptoms (unadjusted weighted-mean effect size r = 0.069, p < 0.0005; adjusted r = 0.046, p < 0.0005; I2 = 46.5%, Q = 11.21, p = 0.08). For IL-6, the association was smaller and lost significance after adjustment (unadjusted r = 0.045, p = 0.007; adjusted r = 0.097, p = 0.06).

Why it matters

These findings suggest that elevated systemic inflammation, particularly elevated CRP, precedes and prospectively associates with the development of depressive symptoms.

Limits

The meta-analysis included a small number of studies (especially for IL-6), evaluated only two markers, showed moderate heterogeneity and evidence of publication bias, and yielded very small effect sizes.

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