Wang Hai-Qiang, Feng Yong-Keng, Hu Xue-Bing, Wu Wei, Lai Xue, Gao Feng, Wang Bin
Department of Pneumology, Wangjing Hospital of China Academy of Chinese Medical Sciences, Beijing, China.
Department of Orthopaedics, Wangjing Hospital of China Academy of Chinese Medical Sciences, Beijing, China.
J Affect Disord. 2025 Dec 1;390:119798. doi: 10.1016/j.jad.2025.119798. Epub 2025 Jul 1.
Observational studies have demonstrated an association between chronic obstructive pulmonary disease (COPD) and structural changes in the brain cortex. However, the causality remains undetermined. This study aims to establish the causal impact of COPD and lung function on brain cortical structure (surface area (SA) and thickness (TH)).
Using Mendelian randomization (MR) analysis. Data from Genome-wide association studies (GWAS) of European ancestry were used. The inverse variance weighted (IVW) method was employed as the primary approach and sensitivity analyses were conducted to examine the robustness of the results.
On the global scale, FVC was significantly positively correlated with brain cortical SA (β = 1644.01 mm, P = 0.01). On a regional scale after Bonferroni correction, forced vital capacity (FVC) was found to be significantly positively correlated with the SA of the medial orbitofrontal without global weighted (β = 30.94 mm, P = 0.00035) and the SA of the middle temporal without global weighted (β = 55.37 mm, P = 0.0003). Forced expiratory volume in one second (FEV1) was significantly negatively correlated with the SA of the frontal pole with global weighted (β = -3.40 mm, P = 0.0003). There were also suggestive evidence showing nominal associations of COPD and lung function with certain brain cortical structures.
These findings suggest that COPD and lung function affect brain cortical structure, indicating the presence of a lung-brain axis.
观察性研究已证明慢性阻塞性肺疾病（COPD）与大脑皮层结构变化之间存在关联。然而，因果关系仍未确定。本研究旨在确定COPD和肺功能对脑皮质结构（表面积（SA）和厚度（TH））的因果影响。
采用孟德尔随机化（MR）分析。使用来自欧洲血统的全基因组关联研究（GWAS）的数据。采用逆方差加权（IVW）方法作为主要方法，并进行敏感性分析以检验结果的稳健性。
在全球范围内，用力肺活量（FVC）与脑皮质SA显著正相关（β = 1644.01mm，P = 0.01）。在Bonferroni校正后的区域尺度上，发现用力肺活量（FVC）与未进行全局加权的内侧眶额皮质SA显著正相关（β = 30.94mm，P = 0.00035）以及与未进行全局加权的颞中回SA显著正相关（β = 55.37mm，P = 0.0003）。一秒用力呼气容积（FEV1）与进行全局加权的额极SA显著负相关（β = -3.40mm，P = 0.0003）。也有提示性证据表明COPD和肺功能与某些脑皮质结构存在名义上的关联。
这些发现表明COPD和肺功能会影响脑皮质结构，提示存在肺-脑轴。
