Depression, C-Reactive Protein, and the Risk of Mortality During Middle and Late Adulthood

Background and Purpose: Mental illnesses, including depression, are major contributors to disability and health loss globally. Research has increasingly focused on identifying biochemical markers, such as C-reactive protein (CRP), to better understand the link between systemic inflammation and psychiatric disorders. However, the long-term health impacts of their coexistence are underexplored. This study aimed to investigate the relationship between depression, elevated CRP levels, and mortality risk among community-dwelling older adults in the United States. Methods: Data from the National Health and Nutrition Examination Survey (NHANES) from 2005–2010 were utilized, linked with mortality data up to December 2019. The sample included 4606 adults aged 50 years and older. Depression was assessed through self-reported measures, and elevated CRP was defined as serum CRP ≥ 2 mg/L. Participants were categorized into four groups: depression only, elevated CRP only, both conditions, or neither. Cox regression models were employed to estimate hazard ratios (HRs) for all-cause and cardiovascular mortality, adjusting for sociodemographic and health-related covariates. Results: Individuals with both depression and elevated CRP had the highest risk of all-cause mortality (HR = 3.56, 95% CI = 1.41–8.97) and cardiovascular mortality (HR = 14.42, 95% CI = 4.29–21.06) compared to those with neither condition. Elevated CRP alone and depression alone were also independently associated with increased mortality risk. Predictors such as age, poverty, smoking, obesity, diabetes, and cardiovascular history significantly influenced these associations. Conclusion: The coexistence of depression and systemic inflammation markedly elevates the risk of mortality. These findings highlight the need for integrated clinical strategies targeting both mental health and inflammation to mitigate mortality risks in vulnerable populations.