Transcriptomic Similarity Informs Neuromorphic Deviations in Depression Biotypes

作者全名："Li, Jiao; Long, Zhiliang; Sheng, Wei; Du, Lian; Qiu, Jiang; Chen, Huafu; Liao, Wei"

作者地址："[Li, Jiao; Sheng, Wei; Chen, Huafu; Liao, Wei] Univ Elect Sci & Technol China, Clin Hosp Chengdu Brain Sci Inst, Sch Life Sci & Technol, Chengdu, Peoples R China; [Li, Jiao; Sheng, Wei; Chen, Huafu; Liao, Wei] Univ Elect Sci & Technol China, MOE Key Lab Neuroinformat, High Field Magnet Resonance Brain Imaging Key Lab, Chengdu, Peoples R China; [Long, Zhiliang; Qiu, Jiang] Southwest Univ, Fac Psychol, Key Lab Cognit & Personal, Chongqing, Peoples R China; [Du, Lian] Chongqing Med Univ, Affiliated Hosp 1, Dept Psychiat, Chongqing, Peoples R China"

通信作者："Liao, W (通讯作者)，Univ Elect Sci & Technol China, Clin Hosp Chengdu Brain Sci Inst, Sch Life Sci & Technol, Chengdu, Peoples R China.; Liao, W (通讯作者)，Univ Elect Sci & Technol China, MOE Key Lab Neuroinformat, High Field Magnet Resonance Brain Imaging Key Lab, Chengdu, Peoples R China."

来源：BIOLOGICAL PSYCHIATRY

ESI学科分类：NEUROSCIENCE & BEHAVIOR

WOS号：WOS:001170711500001

JCR分区：Q1

影响因子：9.6

年份：2024

卷号：95

期号：5

开始页：414

结束页：425

文献类型：Article

关键词：　

摘要："BACKGROUND: Major depressive disorder (MDD) is complicated by population heterogeneity, motivating the investigation of biotypes through imaging-derived phenotypes. However, neuromorphic heterogeneity in MDD remains unclear, and how the correlated gene expression (CGE) connectome constrains these neuromorphic anomalies in MDD biotypes has not yet been studied. METHODS: Here, we related cortical thickness deviations in MDD biotypes to a pattern of CGE connectome. Cortical thickness was estimated from 3-dimensional T1-weighted magnetic resonance images in 2 independent cohorts (discovery cohort: N = 425; replication cohort: N = 217). The transcriptional activity was measured according to Allen Human Brain Atlas. A density peak-based clustering algorithm was used to identify MDD biotypes. RESULTS: We found that patients with MDD were clustered into 2 replicated biotypes based on single-patient regional deviations from healthy control participants across 2 datasets. Biotype 1 mainly exhibited cortical thinning across the brain, whereas biotype 2 mainly showed cortical thickening in the brain. Using brainwide gene expression data, we found that deviations of transcriptionally connected neighbors predicted regional deviation for both biotypes. Furthermore, putative CGE-informed epicenters of biotype 1 were concentrated on the cognitive control circuit, whereas biotype 2 epicenters were located in the social perception circuit. The patterns of epicenter likelihood were separately associated with depression- and anxiety-response maps, suggesting that epicenters of MDD biotypes may be associated with clinical efficacies. CONCLUSIONS: Our findings linked the CGE connectome and neuromorphic deviations to identify distinct epicenters in MDD biotypes, providing insight into how microscale gene expressions informed MDD biotypes."

基金机构："Natural Science Foundation of China [82202250, 62036003, U1808204]; China Postdoctoral Science Foundation [BX2021057, 2022M710615]; Fundamental Research Funds for the Central Universities [ZYG-X2022YGRH008]"

基金资助正文："This work was supported by the National Key Project of Research and Development of Ministry of Science and Technology (Grant Nos.2022YFC2009906 [to WL] and 2022YFC2009900 [to WL]), the National Natural Science Foundation of China (Grant Nos. 82202250 [to JL],62036003 [to HC], and U1808204 [to HC]), the China Postdoctoral Science Foundation (Grant Nos. BX2021057 [JL] and 2022M710615 [to JL]), and the Fundamental Research Funds for the Central Universities (Grant No. ZYG-X2022YGRH008 [to WL]).We thank Dr. Bharat B. Biswal for editing our manuscript.The authors report no biomedicalfinancial interests or potential conflictsof interest.r Natural Science Foundation of China (Grant Nos. 82202250 [to JL] , 62036003 [to HC] , and U1808204 [to HC] ) , the China Postdoctoral Science Foundation (Grant Nos. BX2021057 [JL] and 2022M710615 [to JL] ) , and the Fundamental Research Funds for the Central Universities (Grant No. ZYG-X2022YGRH008 [to WL] ) ."