Gu Si-Chun, Shen Chang-Yi, Deng Jun-Qi, Zhang Wei, Zeng Si-Lu, Hao Yong, Su Hang, Ye Qing
Department of Neurology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, 725 South Wanping Road, Shanghai 200032, China.
Shanghai Mental Health Center, Shanghai Jiaotong University School of Medicine, 600 South Wanping Road, Shanghai 200030, China.
J Affect Disord. 2025 Jul 15;381:551-559. doi: 10.1016/j.jad.2025.03.177. Epub 2025 Apr 1.
Neuropsychiatric disorders, including Alzheimer's disease (AD), major depressive disorder (MDD), anxiety disorders, attention-deficit/hyperactivity disorder (ADHD), bipolar disorder, insomnia, and schizophrenia (SCZ), are prevalent and impose substantial morbidity and mortality worldwide. Brain morphometry, is increasingly recognized for its relevance to cognitive, emotional, and behavioral functions, yet its causal links to neuropsychiatric pathologies are not well established.
This study aimed to explore the causal relationships between cortical thickness (TH) and surface area (SA) with 7 neuropsychiatric disorders using Mendelian randomization (MR) analyses.
We employed data from genome-wide association studies (GWAS) comprising 51,665 individuals to evaluate cortical SA and TH. We selected single nucleotide polymorphisms (SNPs) as instrumental variables for MR analyses to investigate the causal associations with neuropsychiatric disorders.
Increased TH in the paracentral cortex was associated with a reduced risk of ADHD. Similarly, a thicker temporal pole was linked to a lower risk of MDD. The TH of the lingual region showed an inverse association with anxiety disorders. The SA of the fusiform gyrus was associated with AD risk, and morphological variations in the caudal middle frontal cortex, isthmus cingulate cortex, and temporal pole were correlated with bipolar disorder risk. An increased TH of the posterior cingulate cortex was associated with higher insomnia risk, and the TH of the pericalcarine region negatively correlated with SCZ risk.
This research provided novel evidence for the causal role of cerebral cortex morphology in neuropsychiatric disorders, suggesting potential targets for therapeutic intervention.
神经精神疾病，包括阿尔茨海默病（AD）、重度抑郁症（MDD）、焦虑症、注意力缺陷多动障碍（ADHD）、双相情感障碍、失眠症和精神分裂症（SCZ），在全球范围内普遍存在，并造成了相当大的发病率和死亡率。脑形态测量学因其与认知、情感和行为功能的相关性而日益受到认可，但其与神经精神病理学的因果关系尚未完全确立。
本研究旨在利用孟德尔随机化（MR）分析探讨皮质厚度（TH）和表面积（SA）与7种神经精神疾病之间的因果关系。
我们采用了来自包含51665名个体的全基因组关联研究（GWAS）的数据来评估皮质SA和TH。我们选择单核苷酸多态性（SNP）作为MR分析的工具变量，以研究与神经精神疾病的因果关联。
中央旁皮质TH增加与ADHD风险降低相关。同样，颞极较厚与MDD风险较低相关。舌叶区域的TH与焦虑症呈负相关。梭状回的SA与AD风险相关，而额中回后部、扣带回峡部和颞极的形态变化与双相情感障碍风险相关。扣带回后部TH增加与失眠风险较高相关，而距状裂周围区域的TH与SCZ风险呈负相关。
本研究为大脑皮质形态在神经精神疾病中的因果作用提供了新证据，提示了潜在的治疗干预靶点。
