Institute of Digestive Diseases, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing, China; Graduate School, China Academy of Chinese Medical Sciences, Beijing, China.
Dongfang Hospital, Beijing University of Chinese Medicine, China.
J Affect Disord. 2025 Jan 15;369:1153-1160. doi: 10.1016/j.jad.2024.10.057. Epub 2024 Oct 22.
Prospective and cross-sectional studies have reported an association between functional gastrointestinal disorders and anxiety and depression. However, the causal relationship remains uncertain. To clarify this, we utilized Mendelian randomization (MR) to assess the causal effects of common gastrointestinal disorders on cortical structures.
Genome-wide association study (GWAS) data was gathered for functional dyspepsia (FD), irritable bowel syndrome (IBS), and gastroesophageal reflux disease (GERD) from European populations numbering 329,262, 16,792, and 602,604, respectively. GWAS cerebral cortical architecture data for cortical thickness (TH) and surface area (SA) were obtained from 51,665 MRI scans. MR was used to analyze the casual relationship between FD, IBS, GERD, and cortical structures. Inverse-variance weighted, weighted median, and MR-Egger tests were performed as assessment indicators. We also evaluated heterogeneity and pleiotropy.
FD significantly decreases the TH in the rostral anterior cingulate cortex (β = -0.022 mm; 95%CI: -0.035 mm to -0.009 mm; P = 6.89 × 10), and IBS significantly decreases the SA of the pars triangularis (β = -21.91 mm; 95%CI: -32.99 mm to -10.83 mm; P = 1.06 × 10), precuneus (β = -47.53 mm; 95%CI: -73.57 mm to-21.48 mm; P = 3.48 × 10) and superior frontal regions (β = -78.70 mm; 95%CI: -122.61 mm to -34.78 mm; P = 4.4 × 10). At the local functional level, GERD significantly increases the SA of the inferior temporal region (β = -113.58 mm, 95%CI: -113.58 mm to -39.01 mm, P = 6.05 × 10).
FD, IBS and GERD can affect the cerebral cortex architecture through the brain-gut axis, potentially increasing the risks of mental illness and cognitive impairment.
前瞻性和横断面研究报告功能性胃肠疾病与焦虑和抑郁之间存在关联。然而，因果关系仍不确定。为了阐明这一点，我们利用孟德尔随机化（MR）来评估常见胃肠道疾病对皮质结构的因果影响。
从欧洲人群中收集了功能性消化不良（FD）、肠易激综合征（IBS）和胃食管反流病（GERD）的全基因组关联研究（GWAS）数据，数量分别为 329262、16792 和 602604。从 51665 次 MRI 扫描中获得了大脑皮质结构的 GWAS 大脑皮层厚度（TH）和表面积（SA）数据。MR 用于分析 FD、IBS、GERD 与皮质结构之间的因果关系。采用逆方差加权、加权中位数和 MR-Egger 检验作为评估指标。我们还评估了异质性和多效性。
FD 显著降低了额前扣带皮质的 TH（β=-0.022mm；95%CI：-0.035mm 至-0.009mm；P=6.89×10），IBS 显著降低了三角部的 SA（β=-21.91mm；95%CI：-32.99mm 至-10.83mm；P=1.06×10）、楔前叶（β=-47.53mm；95%CI：-73.57mm 至-21.48mm；P=3.48×10）和额上回区域（β=-78.70mm；95%CI：-122.61mm 至-34.78mm；P=4.4×10）。在局部功能水平上，GERD 显著增加了颞下回区域的 SA（β=-113.58mm，95%CI：-113.58mm 至-39.01mm，P=6.05×10）。
FD、IBS 和 GERD 可通过脑-肠轴影响大脑皮质结构，从而增加患精神疾病和认知障碍的风险。
