Background: Increasing evidence suggests that youth with Major Depressive Disorder (MDD) exhibit early indicators of cardiovascular disease. A leading hypothesized mechanism of this association is via inflammatory pathways, however, results examining this direct association are mixed. Our objective was to synthesize and quantify observational studies examining the association of depression and inflammation among children and adolescents.

Methods: Electronic searches were conducted in MEDLINE, Embase, PsycINFO, and Scopus, yielding 2,757 non-duplicate records from 1946 to 2019. The included studies measured depression or depressive symptoms and examined its association with inflammation in participants younger than 18 years. All relevant articles were reviewed and data extracted by two independent coders. Estimates were examined by using random-effects meta-analysis.

Results: Twenty-two studies (20,791 participants) were included. Significant associations were observed between concurrent depression and CRP (n = 7; r = 0.12; 95% confidence interval [CI] = 0.04 to 0.19), and IL-6 (n = 7; r = 0.17; 95% CI= 0.10 to 0.24). Longitudinal analyses revealed that depression is a significant predictor of IL-6 (n = 3; r = 0.29; 95% CI= 0.04 to 0.50) and conversely, that inflammation (measured by CRP or IL-6) predicts future depression (n = 4; r = 0.04; 95% CI= 0.00 to 0.08).

Limitations: Results are limited by the small number of studies preventing examination of some moderator variables. Findings are correlational, not causal.

Conclusion: Depression is positively associated with concurrent and future inflammation among children and adolescents. Results suggest that bidirectional associations may exist between depression and a pro-inflammatory state.