Yao Chi, Wang Peng, Xiao Yang, Zheng Yuhong, Pu Jiayong, Miao Yongwei, Wang Jinghua, Xue Shao-Wei
Center for Cognition and Brain Disorders/Department of Neurology, The Affiliated Hospital, Hangzhou Normal University, No.2318, Yuhangtang Rd, Hangzhou, Zhejiang, China.
Jing Hengyi School of Education, Hangzhou Normal University, Hangzhou, China.
Sci Rep. 2025 Mar 14;15(1):8853. doi: 10.1038/s41598-025-92849-1.
Major depressive disorder (MDD) is a highly heterogeneous psychiatric disorder characterized with considerable individual variability in clinical manifestations which may correspond to brain alterations including the default mode network (DMN). This study analyzed resting-state functional magnetic resonance imaging (rs-fMRI) data from 796 MDD patients and 823 healthy controls (HC) to investigate individual variability in functional connectivity (IVFC) between the DMN and 108 non-DMN regions. We aimed to identify MDD-related IVFC abnormalities and their clinical relevance, alongside exploring gene expression correlations. The results revealed similar spatial patterns of IVFC within the DMN in both groups, yet significantly increased IVFC values in MDD patients were observed in regions such as the ventromedial prefrontal cortex, anterior cingulate cortex, posterior cingulate cortex, fusiform gyrus, and occipital cortex. Notably, the mean IVFC in the DMN and fusiform gyrus was positively correlated with Hamilton Rating Scale for Depression (HAMD) scores in MDD patients. Gene expression analyses explained 47.0% of the variance in MDD-related IVFC alterations, with the most associated genes enriched in processes including membrane potential regulation, head development, synaptic transmission, and dopaminergic synapse. These findings highlight the clinical importance of IVFC variability in the DMN and suggest its potential role as a biomarker in MDD.
重度抑郁症（MDD）是一种高度异质性的精神疾病，其临床表现存在相当大的个体差异，这可能与包括默认模式网络（DMN）在内的大脑改变相对应。本研究分析了796例MDD患者和823例健康对照（HC）的静息态功能磁共振成像（rs-fMRI）数据，以研究DMN与108个非DMN区域之间功能连接性的个体差异（IVFC）。我们旨在识别与MDD相关的IVFC异常及其临床相关性，同时探索基因表达相关性。结果显示，两组DMN内IVFC的空间模式相似，但在MDD患者中，腹内侧前额叶皮质、前扣带回皮质、后扣带回皮质、梭状回和枕叶皮质等区域的IVFC值显著增加。值得注意的是，MDD患者DMN和梭状回的平均IVFC与汉密尔顿抑郁量表（HAMD）评分呈正相关。基因表达分析解释了与MDD相关的IVFC改变中47.0%的变异，最相关的基因富集在包括膜电位调节、头部发育、突触传递和多巴胺能突触等过程中。这些发现突出了DMN中IVFC变异性的临床重要性，并表明其在MDD中作为生物标志物的潜在作用。
