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. 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 (FEV1). 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. 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; FEV1% 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 FEV1% 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. 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.

中文翻译：

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肺功能与抑郁症之间的关联和生物学途径：一项 280,032 名参与者的前瞻性队列研究

人们越来越认识到肺部健康是心理健康的一个重要因素。然而，关于肺功能与抑郁症相关的前瞻性证据仍有待确定。该研究旨在探讨肺功能受损与抑郁症之间的前瞻性关联及其潜在的生物学机制。这项前瞻性队列研究包括 280,032 名非抑郁症个体，这些个体具有英国生物银行的有效肺功能测量结果。通过用力肺活量（FVC）或1秒用力呼气量（FEV1）评估肺功能。应用 Cox 比例风险模型来估计肺功能与抑郁事件之间的关联。中介分析用于研究生物标志物和代谢物在关联中的潜在中介作用。在中位随访 13.91 年期间，共有 9514 名参与者 (3.4%) 出现抑郁症。与最低四分位数的个体相比，最高四分位数的个体患抑郁症的风险较低（FVC % 预测：HR = 0.880，95% CI = 0.830–0.933；FEV1% 预测：HR = 0.854，95% CI = 0.805–0.905）肺功能指数的四分位数。此外，受限三次样条表明肺功能指数与抑郁事件的 J 形关联发生逆转（FVC % 预测和 FEV1% 预测的非线性 P < 0.05）。肺功能受损产生相似的风险估计（HR = 1.124，95% CI = 1.074–1.176）。涉及全身炎症、红细胞以及肝肾功能的生物标志物可能是肺功能-抑郁关联中的潜在介质。这项研究表明，患抑郁症的风险较高与肺功能受损有关。此外，这种关联可能部分由生物标志物介导，包括全身炎症、红细胞以及肝肾功能，但由于潜在的时间模糊性，应谨慎解释这些介导结果。