Mapping Neurophysiological Subtypes of Major Depressive Disorder Using Normative Models of the Functional Connectome

作者全名："Sun, Xiaoyi; Sun, Jinrong; Lu, Xiaowen; Dong, Qiangli; Zhang, Liang; Wang, Wenxu; Liu, Jin; Ma, Qing; Wang, Xiaoqin; Wei, Dongtao; Chen, Yuan; Liu, Bangshan; Huang, Chu-Chung; Zheng, Yanting; Wu, Yankun; Chen, Taolin; Cheng, Yuqi; Xu, Xiufeng; Gong, Qiyong; Si, Tianmei; Qiu, Shijun; Lin, Ching-Po; Cheng, Jingliang; Tang, Yanqing; Wang, Fei; Qiu, Jiang; Xie, Peng; Li, Lingjiang; He, Yong; Xia, Mingrui"

作者地址："[Sun, Xiaoyi; Liu, Jin; Ma, Qing; He, Yong; Xia, Mingrui] Beijing Normal Univ, State Key Lab Cognit Neurosci & Learning, Beijing, Peoples R China; [Sun, Xiaoyi; Liu, Jin; Ma, Qing; He, Yong; Xia, Mingrui] Beijing Normal Univ, Beijing Key Lab Brain Imaging & Connect, Beijing, Peoples R China; [Sun, Xiaoyi; Liu, Jin; Ma, Qing; He, Yong; Xia, Mingrui] Beijing Normal Univ, IDG McGovern Inst Brain Res, Beijing 100875, Peoples R China; [Sun, Xiaoyi; Wang, Wenxu] Beijing Normal Univ, Sch Syst Sci, Beijing, Peoples R China; [Sun, Jinrong; Lu, Xiaowen; Dong, Qiangli; Zhang, Liang; Liu, Bangshan; Li, Lingjiang] Second Xiangya Hosp Cent South Univ, Natl Clin Res Ctr Mental Disorders, Dept Psychiat, Changsha, Hunan, Peoples R China; [Sun, Jinrong; Lu, Xiaowen; Dong, Qiangli; Zhang, Liang; Liu, Bangshan; Li, Lingjiang] Cent South Univ, China Natl Technol Inst Mental Disorders, Hunan Med Ctr Mental Hlth, Hunan Key Lab Psychiat & Mental Hlth,Inst Mental H, Changsha, Hunan, Peoples R China; [Sun, Jinrong] Yangzhou Univ, Yangzhou Mental Hlth Ctr, Affiliated WuTaiShan Hosp, Med Coll, Yangzhou, Jiangsu, Peoples R China; [Lu, Xiaowen] Huazhong Univ Sci & Technol Wuhan, Wuhan Mental Hlth Ctr, Wuhan, Peoples R China; [Dong, Qiangli] Lanzhou Univ, Dept Rheumatol, Hosp 2, Lanzhou, Peoples R China; [Zhang, Liang] Shanghai Univ Med & Hlth Sci, Mental Hlth Educ & Counseling Ctr, Shanghai, Peoples R China; [Ma, Qing] Fudan Univ, Inst Sci & Technol Brain Inspired Intelligence, Shanghai, Peoples R China; [Wang, Xiaoqin; Wei, Dongtao; Qiu, Jiang] Southwest Univ, Key Lab Cognit & Personal, Minist Educ, Chongqing, Peoples R China; [Wang, Xiaoqin; Wei, Dongtao; Qiu, Jiang] Southwest Univ, Dept Psychol, Chongqing, Peoples R China; [Chen, Yuan; Cheng, Jingliang] Zhengzhou Univ, Dept Magnet Resonance Imaging, Affiliated Hosp 1, Zhengzhou, Peoples R China; [Huang, Chu-Chung] East China Normal Univ, Shanghai Key Lab Brain Funct Genom, Affiliated Mental Hlth Ctr, Sch Psychol & Cognit Sci, Shanghai, Peoples R China; [Zheng, Yanting; Qiu, Shijun] Guangzhou Univ Chinese Med, Affiliated Hosp 1, Guangzhou, Peoples R China; [Wu, Yankun; Si, Tianmei] Peking Univ, Hosp 6, Natl Clin Res Ctr Mental Disorders, NHC Key Lab Mental Hlth, Beijing, Peoples R China; [Chen, Taolin; Gong, Qiyong] Sichuan Univ, West China Hosp, Huaxi Magnet Resonance Res Ctr, Dept Radiol, Chengdu, Peoples R China; [Chen, Yuan; Xu, Xiufeng] Kunming Med Univ, Affiliated Hosp 1, Dept Orthopaed, Kunming, Peoples R China; [Gong, Qiyong] Chinese Acad Med Sci, Res Unit Psychoradiol, Chengdu, Sichuan, Peoples R China; [Lin, Ching-Po] Natl Yang Ming Chiao Tung Univ, Inst Neurosci, Taipei, Taiwan; [Lin, Ching-Po] Taipei City Hosp, Dept Res & Educ, Taipei, Taiwan; [Tang, Yanqing; Wang, Fei] China Med Univ, Dept Urol, Affiliated Hosp 1, Shenyang, Peoples R China; [Xie, Peng] Chongqing Key Lab Neurobiol, Chongqing, Peoples R China; [Xie, Peng] Chongqing Med Univ, Dept Neurol, Affiliated Hosp 1, Chongqing, Peoples R China; [He, Yong] Chinese Inst Brain Res, Beijing, Peoples R China"

通信作者："Sun, XY; Xia, MR (通讯作者)，Beijing Normal Univ, State Key Lab Cognit Neurosci & Learning, Beijing, Peoples R China.; Sun, XY; Xia, MR (通讯作者)，Beijing Normal Univ, Beijing Key Lab Brain Imaging & Connect, Beijing, Peoples R China.; Sun, XY; Xia, MR (通讯作者)，Beijing Normal Univ, IDG McGovern Inst Brain Res, Beijing 100875, Peoples R China.; Sun, XY (通讯作者)，Beijing Normal Univ, Sch Syst Sci, Beijing, Peoples R China."

来源：BIOLOGICAL PSYCHIATRY

ESI学科分类：NEUROSCIENCE & BEHAVIOR

WOS号：WOS:001114673100001

JCR分区：Q1

影响因子：9.6

年份：2023

卷号：94

期号：12

开始页：936

结束页：947

文献类型：Article; Early Access

关键词：　

摘要："BACKGROUND: Major depressive disorder (MDD) is a highly heterogeneous disorder that typically emerges in adolescence and can occur throughout adulthood. Studies aimed at quantitatively uncovering the heterogeneity of individual functional connectome abnormalities in MDD and identifying reproducibly distinct neurophysiological MDD subtypes across the lifespan, which could provide promising insights for precise diagnosis and treatment prediction, are still lacking. METHODS: Leveraging resting-state functional magnetic resonance imaging data from 1148 patients with MDD and 1079 healthy control participants (ages 11-93), we conducted the largest multisite analysis to date for neurophysiological MDD subtyping. First, we characterized typical lifespan trajectories of functional connectivity strength based on the normative model and quantitatively mapped the heterogeneous individual deviations among patients with MDD. Then, we identified neurobiological MDD subtypes using an unsupervised clustering algorithm and evaluated intersite reproducibility. Finally, we validated the subtype differences in baseline clinical variables and longitudinal treatment predictive capacity. RESULTS: Our findings indicated great intersubject heterogeneity in the spatial distribution and severity of functional connectome deviations among patients with MDD, which inspired the identification of 2 reproducible neurophysio-logical subtypes. Subtype 1 showed severe deviations, with positive deviations in the default mode, limbic, and subcortical areas and negative deviations in the sensorimotor and attention areas. Subtype 2 showed a moderate but converse deviation pattern. More importantly, subtype differences were observed in depressive item scores and the predictive ability of baseline deviations for antidepressant treatment outcomes. CONCLUSIONS: These findings shed light on our understanding of different neurobiological mechanisms underlying the clinical heterogeneity of MDD and are essential for developing personalized treatments for this disorder."

基金机构："SIT 2030-Major Projects [2022ZD0211500]; National Natural Science Foundation of China [82071998, 82021004, 81920108019, 91649117, 81771344, 81471251]; Beijing Nova Program [Z191100001119023]; Beijing United Imaging Research Institute of Intelligent Imaging Foundation [CRIBJZD202102]; Science and Technology Plan Project of Guangzhou [2018-1002-SF-0442]; Guangzhou Key Laboratory [09002344]; Key R&D Program of Sichuan Province [2023YFS0076]"

基金资助正文："This work was supported by the SIT 2030-Major Projects (Grant No. 2022ZD0211500 [to MX] ) , National Natural Science Foundation of China (Grant No. 82071998 [to MX] ; Grant No. 82021004 [to YH] ; Grant Nos. 81920108019, 91649117, 81771344, and 81471251 [to SQ] ) , Beijing Nova Program (Grant No. Z191100001119023 [to MX] ) , Beijing United Imaging Research Institute of Intelligent Imaging Foundation (Grant No. CRIBJZD202102 [to MX] ) , Science and Technology Plan Project of Guangzhou (Grant No. 2018-1002-SF-0442 [to SQ] ) , Guangzhou Key Laboratory (Grant No. 09002344 [to SQ] ) , and Key R & D Program of Sichuan Province (Grant No. 2023YFS0076 [to TC] ) . A previous version of this article was published as a preprint on bioRxiv: https://doi.org/10.1101/2023.02.13.528399. The authors report no biomedical financial interests or potential conflicts of interest."