Abstract
BACKGROUND AND AIMS: The relationship between depression, sleep duration, and mortality outcomes remains incompletely elucidated. This study aimed to investigate the combined effects of depression and sleep duration on mortality risk, while also examining the potential mediating role of inflammatory markers in these associations. METHODS: The analysis included 41,346 adult participants from the US National Health and Nutrition Examination Survey (NHANES). Mortality outcomes were determined through linkage with the National Death Index (NDI) records up to December 31, 2019. Multivariate Cox proportional hazards regression models were employed to assess the associations between depression, sleep duration, and both all-cause and cardiovascular mortality. Additionally, the mediating effect of C-reactive protein (CRP) was evaluated. RESULTS: Depression was independently associated with elevated risks of both all-cause mortality (HR: 1.40, 95% CI: 1.12-1.74) and cardiovascular mortality (HR: 1.79, 95% CI: 1.21-2.65). Similarly, short sleep duration was independently linked to increased all-cause mortality risk (HR: 1.19, 95% CI: 1.03-1.37). The combination of depression and abnormal sleep duration (either short or long) significantly amplified mortality risks, with long sleep duration showing particularly strong associations (all-cause mortality: HR: 1.84, 95% CI: 1.19-2.85; cardiovascular mortality: HR: 2.28, 95% CI: 1.05-4.95). Mediation analysis suggested that CRP may partially explain the joint associations of depression and sleep duration with both all-cause and cardiovascular mortality. CONCLUSION: The coexistence of depression and abnormal sleep duration is associated with significantly increased mortality risk, with CRP potentially playing a measurable mediating role in these associations.