Shi Lingyi, Zhou Xiangjun, Qu Yucai, Du Zhiqiang, Zhou Qin, Zhou Zhenhe, Jiang Ying, Wang Xinrong, Zhu Haohao
Affiliated Mental Health Center of Jiangnan University, Wuxi Central Rehabilitation Hospital, Wuxi, Jiangsu 214151, China.
Affiliated Mental Health Center of Jiangnan University, Wuxi Central Rehabilitation Hospital, Wuxi, Jiangsu 214151, China.
J Affect Disord. 2025 Apr 1;374:356-364. doi: 10.1016/j.jad.2025.01.069. Epub 2025 Jan 15.
This study aimed to explore the causal relationship between brain cortical and subcortical structures and major depressive disorder (MDD) using the Mendelian Randomization (MR) method.
Single nucleotide polymorphisms (SNPs) were used as instrumental variables to analyze subcortical brain volume, cortical thickness, and surface area as exposure factors, with MDD as the outcome. Multiple sensitivity analyses were conducted to validate the robustness of the results.
MR analysis showed a significant negative correlation between subcortical brain volume and MDD. Specifically, the volumes of the caudate nucleus, hippocampus, intracranial region, and thalamus were inversely associated with the risk of MDD, indicating that larger subcortical brain volumes were linked to a lower risk of MDD. The thickness of the entorhinal cortex was also negatively correlated with MDD. At the same time, certain cortical regions showed significant positive correlations between surface area and MDD. Increased thickness of the entorhinal cortex and increased surface areas of the isthmus of the cingulate gyrus, middle temporal gyrus, and precuneus were associated with a higher risk of MDD. The sensitivity analyses revealed no significant heterogeneity or horizontal pleiotropy, and the results were consistent across different methods, confirming their robustness.
The study found that increased volumes of the caudate nucleus, hippocampus, internal capsule, and thalamus in subcortical brain regions and increased thickness of the entorhinal cortex in cortical regions were associated with a reduced risk of MDD, while increased surface areas of the isthmus of the cingulate gyrus, middle temporal gyrus, and precuneus in cortical regions were linked to an elevated risk of MDD.
本研究旨在采用孟德尔随机化（MR）方法探讨脑皮质和皮质下结构与重度抑郁症（MDD）之间的因果关系。
使用单核苷酸多态性（SNP）作为工具变量，以皮质下脑容量、皮质厚度和表面积作为暴露因素进行分析，以MDD作为结局。进行了多项敏感性分析以验证结果的稳健性。
MR分析显示皮质下脑容量与MDD之间存在显著负相关。具体而言，尾状核、海马体、颅内区域和丘脑的体积与MDD风险呈负相关，表明较大的皮质下脑容量与较低的MDD风险相关。内嗅皮质的厚度也与MDD呈负相关。同时，某些皮质区域的表面积与MDD之间存在显著正相关。内嗅皮质厚度增加以及扣带回峡部、颞中回和楔前叶表面积增加与较高的MDD风险相关。敏感性分析未发现显著的异质性或水平多效性，且不同方法的结果一致，证实了结果的稳健性。
该研究发现，皮质下脑区尾状核、海马体、内囊和丘脑体积增加以及皮质区内嗅皮质厚度增加与较低的MDD风险相关，而皮质区扣带回峡部、颞中回和楔前叶表面积增加与较高的MDD风险相关。
