Association between sleep disturbances and circulating inflammatory markers in depressive and bipolar disorders: a...

Evidence of a connection between sleep disturbances (i.e., difficulties in sleep onset or sleep maintenance) and inflammation in major depression (MDD) and bipolar (BD) disorders is still under debate. Here, we report a systematic review and meta-analysis on the correlation between sleep disturbances and peripheral proinflammatory markers in adult individuals with MDD or BD. The review followed the PRISMA guidelines and was registered in PROSPERO (CRD42025638037). Pubmed, Scopus, PsycInfo, Web of Science, MEDLINE, and CINAHL were searched up to January 2025. Of the 5694 articles retrieved, 21 studies met the inclusion criteria and were considered for the systematic review; 13 reported data for meta-analysis. DerSimonian and Laird random effect models showed that subjective sleep disturbances were significantly associated with pooled inflammatory markers (k = 13, n = 5261, r = .12, 95 % CI = .056 to .175, p < .001) and specifically C-reactive protein (CRP) levels (k = 8, n = 4949, r = .08, 95 % CI = .018 to .147, p = .012) in MDD patients. Meta-regressions revealed no evidence of moderation by BMI and sex. Analysis on interleukins (IL-6, IL-1β, IL-8), and tumour necrosis factor-α (TNF-α), did not reach statistical significance. The number of studies in BD patients did not suffice meta-analysis. While results may suggest a sleep-immune cross-talk in the pathophysiology of MDD, findings should be interpreted in light of the substantial meta-analytic heterogeneity.