Review: Inflammation and anxiety‐based disorders in children and adolescents – a systematic review and meta‐analysis

BACKGROUND Anxiety-based disorders are common and are often chronic with an onset during childhood or adolescence. An emerging literature has examined the role of inflammation in these disorders by measuring blood concentrations of inflammatory markers such as cytokines, C-reactive protein (CRP) and immune markers such as white blood cell counts. However, existing results are inconsistent, with available meta-analyses only including adult populations. We believe this is the first systematic review and meta-analysis to investigate these inconsistencies among the population of children and adolescents. METHODS A systematic search of five electronic databases was conducted to identify studies which compared inflammatory markers between individuals with an anxiety-based disorder and healthy controls. Study quality was assessed, and pooled effect sizes (Hedges' g) were calculated using random-effects meta-analyses. RESULTS Nine independent studies were identified. The combined meta-analysis of 16 cytokines and CRP was approaching significance; however, no significant between-group difference was observed for meta-analyses of individual inflammatory or immune markers. Heterogeneity was high, and quality assessments identified important limitations; primarily, small sample sizes and a lack of control over confounding variables. CONCLUSIONS Although no significant effects were observed, the small number of included studies and limitations in study or reporting quality render these findings provisional. Research in this area has the potential for important clinical implications in relation to therapeutic interventions. Important recommendations for further research are put forth.