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.

Longitudinal association between sleep disturbance and inflammation, and the role of positive affect.

Previous longitudinal evidence suggested that sleep disturbance (i.e., difficulties in sleep onset and sleep maintenance) may be longitudinally associated with systemic inflammation, which is involved in the pathophysiology of mental and somatic illness. The mechanisms underlying this association, however, remain largely unexplored. In the context of health psychology, a substantial body of literature showed that positive affect may have a favourable impact on immune and inflammatory response and buffer the proinflammatory effects of stress. Therefore, the aim of this study was to assess whether subjective sleep disturbance is longitudinally associated with serum high sensitivity C-reactive protein (hs-CRP), a marker of systemic inflammation, and whether this association is mediated by a decrease in positive affect. The data of 1894 participants aged 64.11 ± 8.02 years from the English Longitudinal Study of Ageing (ELSA) across three waves of data collection were analysed. Self-reported sleep disturbance was assessed in 2008-2009, (wave 4), positive affect was assessed in 2010-2011 (wave 5), and hs-CRP was assessed in 2012-2013 (wave 6). Path analysis adjusted for health-related variables including depressive symptoms, cardiovascular disease, BMI, smoking, alcohol consume, and drug intake showed a significant direct effect of sleep disturbance to positive affect; positive affect directly predicted hs-CRP. Lastly, an indirect effect between sleep disturbance to hs-CRP through the mediating role of positive affect emerged. The findings suggest that sleep onset and sleep maintenance difficulties may be associated with inflammation through the mediation of low positive affect. The clinical significance of the findings should be further explored.

A meta-analysis on sleep quality in inflammatory bowel disease.

Evidence of poor sleep quality in inflammatory bowel disease (IBD, i.e., Crohn's disease and ulcerative colitis) has been reported but never systematically reviewed or meta-analysed. We conducted a systematic review and meta-analysis of pairwise comparisons that included 1) IBD patients/controls, 2) Crohn's disease/ulcerative colitis, 3) active/inactive IBD on standardised measures of sleep quality. PubMed, Medline, PsycINFO, Scopus, and CINAHL were searched up to March 2021. Forty-two studies met the inclusion criteria. Results showed poorer subjective sleep quality in IBD patients than in controls, with moderate effect sizes (g = .49, [95% CI = .32 - .66], p < .001). No differences within IBD subtypes were found (g = -.07, [95% CI = -.17-.05], p = .208). Individuals with an active IBD reported poorer sleep quality than those in remission, with a large effect size (g = .66, [95% CI = .35 - .98], p < .001). Results on objectively recorded sleep were mixed, with no clear evidence of objective sleep impairments in individuals with IBD. Results support the view of subjective poor sleep quality as a relevant comorbidity in IBD. As a potential factor affecting immune and inflammatory responses as well as patients' quality of life, sleep quality should be taken into account in the treatment of IBD.