Causal Association Between Major Depressive Disorder and Cortical Structure: A Bidirectional Mendelian Randomization Study and Mediation Analysis

IF 4.8 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics Pub Date : 2025-03-09 DOI:10.1111/cns.70319

Hui Zheng, Yong-Jiang Fang, Xiao-Ying Wang, Si-Jia Feng, Tai-Chun Tang, Min Chen

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Abstract

Background

Previous observational studies have reported a possible association between major depressive disorder (MDD) and abnormal cortical structure. However, it is unclear whether MDD causes reductions in global cortical thickness (CT) and global area (SA). Objective: We aimed to test the bidirectional causal relationship between MDD and CT and SA using a Mendelian randomization (MR) design and performed exploratory analyses of MDD on CT and SA in different brain regions.

Methods

Summary-level data were obtained from two GWAS meta-analysis studies: one screening for single nucleotide polymorphisms (SNPs) predicting the development of MDD (n = 135,458) and the other identifying SNPs predicting the magnitude of cortical thickness (CT) and surface area (SA) (n = 51,665).

Results

The results showed that MDD caused a decrease in CT in the medial orbitofrontal region, a decrease in SA in the paracentral region, and an increase in SA in the lateral occipital region. C-reactive protein, tumor necrosis factor alpha (TNF-α), interleukin-1β, and interleukin-6 did not mediate the reduction. We also found that a reduction in CT in the precentral region and a reduction in SA in the orbitofrontal regions might be associated with a higher risk of MDD. Conclusion: Our study did not suggest an association between MDD and cortical CT and SA.

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重度抑郁症与大脑皮层结构的因果关系：双向孟德尔随机化研究和中介分析

背景先前的观察性研究已经报道了重度抑郁症（MDD）与皮层结构异常之间可能存在的关联。然而，目前尚不清楚MDD是否会导致整体皮质厚度（CT）和整体面积（SA）的减少。目的：采用孟德尔随机化（Mendelian randomization， MR）设计检验MDD与CT和SA之间的双向因果关系，并对不同脑区MDD对CT和SA的影响进行探索性分析。方法从两项GWAS荟萃分析研究中获得汇总数据：一项是筛选预测MDD发展的单核苷酸多态性（SNPs）（n = 135,458），另一项是识别预测皮质厚度（CT）和表面积（SA）大小的SNPs （n = 51,665）。结果MDD导致眶额内侧区CT降低，中央旁区SA降低，枕外侧区SA升高。c反应蛋白、肿瘤坏死因子α (TNF-α)、白细胞介素-1β和白细胞介素-6没有介导减少。我们还发现，中央前区CT的减少和眶额区SA的减少可能与MDD的高风险相关。结论：我们的研究并未提示MDD与皮质CT和SA之间存在关联。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

CNS Neuroscience & Therapeutics 医学-神经科学

CiteScore

7.30

自引率

12.70%

发文量

240

审稿时长

2 months

期刊介绍： CNS Neuroscience & Therapeutics provides a medium for rapid publication of original clinical, experimental, and translational research papers, timely reviews and reports of novel findings of therapeutic relevance to the central nervous system, as well as papers related to clinical pharmacology, drug development and novel methodologies for drug evaluation. The journal focuses on neurological and psychiatric diseases such as stroke, Parkinson’s disease, Alzheimer’s disease, depression, schizophrenia, epilepsy, and drug abuse.