The Association Between Depression and Idiopathic Pulmonary Fibrosis: A Prospective Study in the UK Biobank

BACKGROUND: Although depression has been associated with various chronic diseases, its relationship with idiopathic pulmonary fibrosis (IPF) remains unclear. METHODS: We included 353,855 participants from the UK Biobank. Depression was defined as (1) clinically diagnosed depression based on linked hospital records and self-reported physician diagnosis, and (2) depressive symptoms assessed by the Patient Health Questionnaire-2 (PHQ-2). We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between depression and incident IPF. Causal mediation analysis was conducted using the R ‘mediation’ package to identify potential mediators of the depression-IPF association. RESULTS: During a mean follow-up period of 14.5 years, we identified 2,261 new cases of IPF among the 353,855 participants in the study. Individuals with depression had a 52% higher risk of developing IPF compared to those without depression (HR: 1.52; 95% CI: 1.33–1.73). Mediation analysis indicated that aging, metabolism, obesity, and inflammation significantly mediated the relationship between depression and the risk of IPF (p < 0.05 for all). CONCLUSIONS: Our findings suggest that individuals with depression are at an elevated risk of IPF. The association between depression and IPF appears to be partially mediated by factors such as aging, metabolism, obesity, and inflammation.