Association and biological pathways between lung function and incident depression: a prospective cohort study of 280,032 participants

Abstract Background Lung health is increasingly recognized as an essential factor in mental health. However, prospective evidence on lung function with incident depression remains to be determined. The study aimed to examine the prospective association between impaired lung function and incident depression and the underlying biological mechanisms. Methods This prospective cohort study comprised 280,032 non-depressed individuals with valid lung function measurements from the UK Biobank. Lung function was assessed through the forced vital capacity (FVC) or forced expiratory volume in 1 s (FEV 1 ). Cox proportional hazard models were applied to estimate the associations between lung function and incident depression. Mediation analyses were fitted to investigate the potential mediating role of biomarkers and metabolites in the association. Results A total of 9514 participants (3.4%) developed depression during a median follow-up of 13.91 years. Individuals in the highest quartile had a lower risk of depression (FVC % predicted: HR = 0.880, 95% CI = 0.830–0.933; FEV 1 % predicted: HR = 0.854, 95% CI = 0.805–0.905) compared with those in the lowest quartile of the lung function indices. Additionally, the restricted cubic splines suggested lung function indices had reversed J-shaped associations with incident depression (nonlinear P < 0.05 for FVC % predicted and FEV 1 % predicted). Impaired lung function yielded similar risk estimates (HR = 1.124, 95% CI = 1.074–1.176). Biomarkers involving systemic inflammation, erythrocytes, and liver and renal function may be potential mediators in the lung function-depression association. Conclusions This study revealed that the higher risk of developing depression was associated with impaired lung function. Also, the association might be partially mediated by biomarkers including systemic inflammation, erythrocytes, and liver and renal function, though these mediation findings should be interpreted with caution due to potential temporal ambiguity.