Wang Wenqin, Jia Wenhui, Wang Shaoying, Wang Ying, Zhang Zhihui, Lei Minghuan, Zhai Ying, Xu Jinglei, Sun Jinghan, Zhang Wanwan, Wang Yao, Jiang Yurong, Jiang Yifan, Liu Mengge, Sun Zuhao, Liu Feng
School of Mathematical Sciences, Tiangong University, Tianjin 300387, China.
School of Mathematical Sciences, Tiangong University, Tianjin 300387, China.
Brain Res. 2024 Oct 1;1840:149049. doi: 10.1016/j.brainres.2024.149049. Epub 2024 May 31.
Previous studies have revealed structural brain abnormalities in individuals with depression, but the causal relationship between depression and brain structure remains unclear.
A genetic correlation analysis was conducted using summary statistics from the largest genome-wide association studies for depression (N = 674,452) and 1,265 brain structural imaging-derived phenotypes (IDPs, N = 33,224). Subsequently, a bidirectional two-sample Mendelian Randomization (MR) approach was employed to explore the causal relationships between depression and the IDPs that showed genetic correlations with depression. The main MR results were obtained using the inverse variance weighted (IVW) method, and other MR methods were further employed to ensure the reliability of the findings.
Ninety structural IDPs were identified as being genetically correlated with depression and were included in the MR analyses. The IVW MR results indicated that reductions in the volume of several brain regions, including the bilateral subcallosal cortex, right medial orbitofrontal cortex, and right middle-posterior part of the cingulate cortex, were causally linked to an increased risk of depression. Additionally, decreases in surface area of the right middle temporal visual area, right middle temporal cortex, right inferior temporal cortex, and right middle-posterior part of the cingulate cortex were causally associated with a heightened risk of depression. Validation and sensitivity analyses supported the robustness of these findings. However, no evidence was found for a causal effect of depression on structural IDPs.
Our findings reveal the causal influence of specific brain structures on depression, providing evidence to consider brain structural changes in the etiology and treatment of depression.
先前的研究已经揭示了抑郁症患者存在大脑结构异常，但抑郁症与大脑结构之间的因果关系仍不清楚。
使用来自最大规模的抑郁症全基因组关联研究（N = 674,452）和1265种源自脑结构成像的表型（IDPs，N = 33,224）的汇总统计数据进行遗传相关性分析。随后，采用双向双样本孟德尔随机化（MR）方法来探究抑郁症与那些显示出与抑郁症存在遗传相关性的IDPs之间的因果关系。主要的MR结果采用逆方差加权（IVW）方法获得，并且进一步使用其他MR方法来确保研究结果的可靠性。
90种结构IDPs被确定与抑郁症存在遗传相关性，并被纳入MR分析。IVW MR结果表明，包括双侧胼胝体下皮质、右侧眶额内侧皮质以及扣带回皮质右侧中后部在内的几个脑区体积减小与抑郁症风险增加存在因果关联。此外，右侧颞中视觉区、右侧颞中皮质、右侧颞下皮质以及扣带回皮质右侧中后部的表面积减小与抑郁症风险升高存在因果关系。验证和敏感性分析支持了这些研究结果的稳健性。然而，未发现抑郁症对结构IDPs有因果效应的证据。
我们的研究结果揭示了特定脑结构对抑郁症的因果影响，为在抑郁症的病因学和治疗中考虑脑结构变化提供了证据。
