Transcriptomic decoding of regional cortical vulnerability to major depressive disorder
Jiajia Zhu, Xiao Chen, Bin Lü, Xue-Ying Li, Zihan Wang, Liping Cao, Guanmao Chen, Jiangshan Chen, Tao Chen, Tao-Lin Chen, Yu-Qi Cheng, Zhaosong Chu, Shi‐Xian Cui, Xi-Long Cui, Zhao‐Yu Deng, Qiyong Gong, Wenbin Guo, Cancan He, Zheng-Jia-Yi Hu, Qian Huang, Xinlei Ji, Feng-Nan Jia, Li Kuang, Baojuan Li, Feng Li, Hui-Xian Li, Tao Li, Tao Lian, Yi‐Fan Liao, Xiaoyun Liu, Yan-Song Liu, Zhe-Ning Liu, Yi-Cheng Long, Jianping Lu, Jiang Qiu, Xiaoxiao Shan, Tian-Mei Si, Peng-Feng Sun, Chuanyue Wang, Huaning Wang, Xiang Wang, Ying Wang, Yuwei Wang, Xiaoping Wu, Xin-Ran Wu, Yankun Wu, Chunming Xie, Guang-Rong Xie, Peng Xie, Xiu-Feng Xu, Zhenpeng Xue, Hong Yang, Yu Hua, Minlan Yuan, Yonggui Yuan, Ai-Xia Zhang, Jingping Zhao, Ke-Rang Zhang, Wei Zhang, Zijing Zhang, Chao‐Gan Yan, Yongqiang Yu
Abstract
Previous studies in small samples have identified inconsistent cortical abnormalities in major depressive disorder (MDD). Despite genetic influences on MDD and the brain, it is unclear how genetic risk for MDD is translated into spatially patterned cortical vulnerability. Here, we initially examined voxel-wise differences in cortical function and structure using the largest multi-modal MRI data from 1660 MDD patients and 1341 controls. Combined with the Allen Human Brain Atlas, we then adopted transcription-neuroimaging spatial correlation and the newly developed ensemble-based gene category enrichment analysis to identify gene categories with expression related to cortical changes in MDD. Results showed that patients had relatively circumscribed impairments in local functional properties and broadly distributed disruptions in global functional connectivity, consistently characterized by hyper-function in associative areas and hypo-function in primary regions. Moreover, the local functional alterations were correlated with genes enriched for biological functions related to MDD in general (e.g., endoplasmic reticulum stress, mitogen-activated protein kinase, histone acetylation, and DNA methylation); and the global functional connectivity changes were associated with not only MDD-general, but also brain-relevant genes (e.g., neuron, synapse, axon, glial cell, and neurotransmitters). Our findings may provide important insights into the transcriptomic signatures of regional cortical vulnerability to MDD.