Inflammation as a mediator between adverse childhood experiences and adult depression: A meta-analytic structural equation model

Exposure to adverse childhood experiences (ACEs) confers a higher risk of developing depression in adulthood, yet the mediation of inflammation remains under debate. To test this model, we conducted a systematic review and two-stage structural equation modelling meta-analysis of studies reporting correlations between ACEs before age 18, inflammatory markers and depression severity in adulthood. Scopus, Pubmed, Medline, PsycInfo, and CINAHL were searched up to 2 October 2023. Twenty-two studies reporting data on C-reactive protein (CRP, n = 12,935), interleukin-6 (IL-6, n = 4108), tumour necrosis factor-α (TNF-α, n = 2256) and composite measures of inflammation (n = 1674) were included. Unadjusted models revealed that CRP (β = 0.003, 95 % LBCI 0.0002 to 0.0068), IL-6 (β = 0.003, 95 % LBCI 0.001 to 0.006), and composite inflammation (β = 0.009, 95 % LBCI 0.004 to 0.018) significantly mediated the association between ACEs and adult depression. The mediation effects no longer survived after adjusting for BMI; however, a serial mediation model revealed that BMI and IL-6 sequentially mediated the association between ACEs and depression (β = 0.002, 95 % LBCI 0.0005 to 0.0046), accounting for 14.59 % and 9.94 % of the variance of IL-6 and depressive symptoms, respectively. Due to the cross-sectional nature of assessment of inflammation and depression findings should be approached with caution; however, results suggest that complex interactions of psychoneuroimmunological and metabolic factors underlie the association between ACEs and adulthood depression.