Inflammatory Cytokines in Children and Adolescents with Depressive Disorders: A Systematic Review and Meta-Analysis

Objective: Meta-analytic evidence shows alterations of peripheral inflammatory cytokines in adults with depressive disorders. By contrast, no evidence synthesis on alterations of peripheral inflammatory cytokines in children/adolescents with depressive disorders is available to date. To fill this gap, we conducted a systematic review and meta-analysis of case-control studies comparing serum cytokine levels in children/adolescents with depressive disorders and healthy controls. Methods: Based on a preregistered protocol (PROSPERO-CRD42018095418), we searched PubMed, Ovid, and Web of Knowledge from inception through July 21, 2018, with no language restrictions, and contacted study authors for unpublished data/information. Random-effects model was used to compute effect size for each cytokine. The Newcastle-Ottawa Scale was used to asses study bias. Results: From a pool of 4231 nonduplicate, potentially relevant references, 8 studies were retained for the qualitative synthesis and 5 for the meta-analysis. TNF-α was higher in participants with depressive disorders versus controls, falling short of statistical significance. Conclusions: Overall, due to the small number of studies, in contrast to the literature in adults, further evidence is needed to confirm possible inflammatory alterations associated with depression in youth.