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 (ß = 0.003, 95 % LBCI 0.0002 to 0.0068), IL-6 (ß = 0.003, 95 % LBCI 0.001 to 0.006), and composite inflammation (ß = 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 (ß = 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.

Inflammation as an aetiological trigger for depressive symptoms in a prospective cohort of patients with inflammatory bowel disease.

OBJECTIVE: Inflammatory bowel disease (IBD) is often comorbid with mood disorders and depressive symptoms. The aetiology of depressive symptoms in IBD, however, remains largely unknown. Consistent with the inflammatory hypothesis of depression, the aim of this study was to explore the prospective associations between inflammatory biomarkers and depressive symptoms in a cohort of IBD patients with and without a previous clinical diagnosis of mood disorder. METHOD: IBD clinical activity was determined using the Harvey-Bradshaw Index for CD and the Partial Mayo score for UC; serum C-reactive protein (CRP) and faecal calprotectin (fCAL) were used as biomarkers of systemic and intestinal inflammation, respectively. Participants were administered the Hospital Anxiety and Depression Scale-depression (HADS-D) at baseline and 1-year follow-up. RESULTS: Eighty-four participants (50 ± 16 years; 75% UC and 25% CD) were included in the main analyses. Longitudinal moderated regression models showed that baseline CRP significantly predicted follow-up HADS-D scores among individuals with a previous mood disorder diagnosis (ß = 0.843, p < .001), but not among individuals without (ß = -0.013, p = .896), after controlling for baseline HADS-D scores, body mass index, IBD phenotype, sex, and perceived stress. Likely due to lower power, results on FCAL (n = 31) were not statistically significant. CONCLUSION: This study suggests that IBD patients with previous diagnosis of mood disorder may be at higher risk of inflammation-related depressive symptoms.