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Transcriptomic decoding of regional cortical vulnerability to major depressive disorder

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机构： [1]Department of Radiology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China. [2]Research Center of Clinical Medical Imaging, Anhui Province Hefei 230032, China. [3]Anhui Provincial Institute of Translational Medicine, Hefei 230032, China. [4]CAS Key Laboratory of Behavioral Science, Institute of Psychology, Chinese Academy of Sciences, Beijing 100101, China. [5]International Big-Data Center for Depression Research, Chinese Academy of Sciences, Beijing 100101, China. [6]Magnetic Resonance Imaging Research Center, Institute of Psychology, Chinese Academy of Sciences, Beijing 100101, China. [7]Department of Psychology, University of Chinese Academy of Sciences, Beijing 100049, China. [8]Affiliated Brain Hospital of GuangzhouMedical University, Guangzhou 510370, China. [9]The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong 250024, China. [10]Department of Radiology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, China. [11]Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University, Chengdu, Sichuan 610044, China. [12]Research Unit of Psychoradiology, Chinese Academy of Medical Sciences, Chengdu, Sichuan 610052, China. [13]Department of Psychiatry, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, China. [14]Sino-Danish College, University of Chinese Academy of Sciences, Beijing 101408, China. [15]Sino-Danish Center for Education and Research, Graduate University of Chinese Academy of Sciences, Beijing 101408, China. [16]Department of Psychiatry, and National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha 410011 Hunan, China. [17]Department of Neurology, Affiliated ZhongDa Hospital of Southeast University, Nanjing, Jiangsu 210009, China. [18]Department of Psychiatry, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400042, China. [19]Department of Clinical Psychology,SuzhouPsychiatric Hospital, The Affiliated Guangji Hospital ofSoochowUniversity,Suzhou, Jiangsu 215003,China. [20]Xijing Hospital of Air ForceMilitaryMedical University, Xi’an,Shaanxi 710032,China. [21]Beijing Anding Hospital, Capital Medical University, Beijing 100120, China. [22]Affiliated Mental Health Center & Hangzhou Seventh People’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310063, China. [23]Mental Health Center and Psychiatric Laboratory, West China Hospital of Sichuan University, Chengdu, Sichuan 610044, China. [24]Department of Psychosomatics and Psychiatry, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu 210009, China. [25]Shenzhen Kangning Hospital Shenzhen, Guangzhou 518020, China. [26]Faculty of Psychology, Southwest University, Chongqing 400715, China. [27]National Clinical Research CenterforMentalDisorders (Peking University Sixth Hospital) & Key Laboratory ofMental Health,Ministry of Health (Peking University),Beijing 100191, China. [28]Xi’an Central Hospital, Xi’an, Shaanxi 710004, China. [29]Institute of Neuroscience, Chongqing Medical University, Chongqing 400016, China. [30]Chongqing Key Laboratory of Neurobiology, Chongqing 400000, China. [31]Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400042, China. [32]West China Hospital of Sichuan University, Chengdu, Sichuan 610044, China. [33]First Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, China

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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. Our combined large-scale neuroimaging and brain transcriptome study demonstrates genetic substrates underlying cortical functional abnormalities in depression, suggesting transcriptomic decoding of regional cortical vulnerability to depression.

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生物学

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Q1 BIOLOGY

影响因子： 5.2 最新[2023版] 5.6 最新五年平均 0 出版当年[2024版] 0 出版当年五年平均 5.2 出版前一年[2023版]

第一作者：

第一作者机构： [1]Department of Radiology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China. [2]Research Center of Clinical Medical Imaging, Anhui Province Hefei 230032, China. [3]Anhui Provincial Institute of Translational Medicine, Hefei 230032, China.

通讯作者：

通讯机构： [1]Department of Radiology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China. [2]Research Center of Clinical Medical Imaging, Anhui Province Hefei 230032, China. [3]Anhui Provincial Institute of Translational Medicine, Hefei 230032, China.

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