Yao Chi, Xiao Yang, Wang Peng, Zheng Yuhong, Sun Jie, Wang Jinhui, Xue Shao-Wei
Center for Cognition and Brain Disorders, Department of Neurology, The Affiliated Hospital, Hangzhou Normal University, Hangzhou, China; Jing Hengyi School of Education, Hangzhou Normal University, Hangzhou, China.
Peking University Sixth Hospital, Peking University, Beijing, China.
J Affect Disord. 2025 Dec 15;391:119985. doi: 10.1016/j.jad.2025.119985. Epub 2025 Jul 27.
Major depressive disorder (MDD) exhibits considerable heterogeneity, with marked inter-subject variability in clinical manifestations, which may reflect differences in brain function and structure. Thereinto, the inter-subject variability of morphological brain networks in MDD remains largely unexamined.
Data from 669 patients with MDD and 706 healthy controls (HC) were obtained from the REST-meta-MDD project. Morphological brain networks were constructed, and the inter-subject variability of morphological connectivity (IVMC) was calculated based on interregional similarity in gray matter volume distribution using the Kullback-Leibler divergence measure. Alterations in IVMC patterns in MDD patients and their clinical relevance were investigated. Additionally, correlations between MDD-related IVMC alterations and densities of neurotransmitter systems, as well as gene expression information, were assessed.
Our analysis revealed altered IVMC patterns in MDD, characterized by increased IVMC within the limbic network (LIM) and ventral attention network (VAN) and decreased IVMC in the frontoparietal network (FPN). These altered IVMC patterns were spatially correlated with densities of neurotransmitter systems, including serotonin and dopamine receptors, and gene expression enriched in transmembrane and molecular transport, signal transduction, and immune response pathways.
Our findings demonstrate an abnormal distribution of IVMC in MDD patients, highlighting potential underlying neurochemical and genetic mechanisms. These results contribute to our understanding of the inter-subject variability observed in MDD and provide insights into the neurophysiological mechanisms underlying the disorder.
重度抑郁症（MDD）表现出相当大的异质性，临床表现存在显著的个体间差异，这可能反映了脑功能和结构的差异。其中，MDD患者脑形态网络的个体间差异在很大程度上仍未得到研究。
从REST-meta-MDD项目中获取了669例MDD患者和706名健康对照（HC）的数据。构建脑形态网络，并使用库尔贝克-莱布勒散度测度基于灰质体积分布的区域间相似性计算形态连接性的个体间差异（IVMC）。研究了MDD患者IVMC模式的改变及其临床相关性。此外，还评估了与MDD相关的IVMC改变与神经递质系统密度以及基因表达信息之间的相关性。
我们的分析揭示了MDD患者IVMC模式的改变，其特征为边缘网络（LIM）和腹侧注意网络（VAN）内的IVMC增加，而额顶网络（FPN）中的IVMC减少。这些改变的IVMC模式在空间上与神经递质系统的密度相关，包括血清素和多巴胺受体，以及在跨膜和分子运输、信号转导和免疫反应途径中富集的基因表达。
我们的研究结果表明MDD患者IVMC分布异常，突出了潜在的神经化学和遗传机制。这些结果有助于我们理解MDD中观察到的个体间差异，并为该疾病潜在的神经生理机制提供了见解。
