Plasma proteomics identifies proteins and pathways associated with incident depression in 46,165 adults  

血浆蛋白质组学揭示抑郁症发病的关键蛋白质及其关联通路:基于46,165名成年人的研究

作　　者：Jujiao Kang Liu Yang Tianye Jia Wei Zhang Lin-Bo Wang Yu-Jie Zhao Jia You Yue-Ting Deng Yi-Jun Ge Wei-Shi Liu Yi Zhang Yi-Lin Chen Xiao-Yu He Barbara J.Sahakian Yucheng TYang Xing-Ming Zhao Jin-Tai Yu Jianfeng Feng Wei Cheng 康菊姣;杨柳;贾天野;张威;王林波;赵钰洁;尤佳;邓悦婷;葛怡君;柳伟仕;张一;陈依琳;何晓宇;Barbara J.Sahakian;杨禹丞;赵兴明;郁金泰;冯建峰;程炜

机构地区：[1]Institute of Science and Technology for Brain-Inspired Intelligence(ISTBI),Fudan University,Shanghai 200433,China [2]Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence,Fudan University,Ministry of Education,Shanghai 200433,China [3]Department of Neurology and National Center for Neurological Disorders,Huashan Hospital,State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science,Shanghai Medical College,Fudan University,Shanghai 200433,China [4]Department of Psychiatry,University of Cambridge,Cambridge CB20SZ,UK [5]Department of Computer Science,University of Warwick,Coventry CV47AL,UK [6]School of Data Science,Fudan University,Shanghai 200438,China

出　　处：《Science Bulletin》2025年第4期573-586,共14页科学通报(英文版)

基　　金：supported by the National Key R&D Program of China(2018YFC1312904 and 2019YFA0709502);the Shanghai Municipal Science and Technology Major Project(2018SHZDZX01);the 111 Project(B18015);Shanghai Center for Brain Science and Brain-Inspired Technology,Zhangjiang Lab,the National Natural Science Foundation of China(82472055 and 82071997)and the Shanghai Rising-Star Program(21QA1408700);the Science and Technology Innovation 2030 Major Projects(2022ZD0211600);National Natural Science Foundation of China(82071201,81971032,and 92249305);Shanghai Municipal Science and Technology Major Project(2018SHZDZX01),Research Start-up Fund of Huashan Hospital(2022QD002);Excellence 2025 Talent Cultivation Program at Fudan University(3030277001);Shanghai Talent Development Funding for The Project(2019074);ZHANGJIANG LAB,Tianqiao and Chrissy Chen Institute,and the State Key Laboratory of Neurobiology and Frontiers Center for Brain Science of Ministry of Education,Fudan University,National Key R&D Program of China(2019YFA0709501);the National Natural Science Foundation of China(T2122005,81801773).

摘　　要：Proteomic alterations preceding the onset of depression offer valuable insights into its development and potential interventions.Leveraging data from 46,165 UK Biobank participants and 2920 plasma proteins profiled at baseline,we conducted a longitudinal analysis with a median follow-up of 14.5 years to explore the relationship between plasma proteins and incident depression.Linear regression was then used to assess associations between depression-related proteins and brain structures,genetic factors,and stress-related events.Our analysis identified 157 proteins associated with incident depression(P<1.71×10^(-5)),including novel associations with proteins such as GAST,PLAUR,LRRN1,BCAN,and ITGA11.Notably,higher expression levels of GDF15(P=6.18×10-26)and PLAUR(P=2.88×10^(-14))were linked to an increased risk of depression,whereas higher levels of LRRN1(P=4.28×10^(-11))and ITGA11(P=3.68×10^(-9))were associated with a decreased risk.Dysregulation of the 157 proteins is correlated with brain regions implicated in depression,including the hippocampus and middle temporal gyrus.Additionally,these protein alterations were strongly correlated with stress-related events,including self-harm events,adult,and childhood trauma.Biological pathway enrichment analysis highlighted the critical roles of the immune response.EGFR and TNF emerged as key proteins in the protein-protein interaction network.BTN3A2,newly linked to incident depression(P=4.35×10^(-10)),was confirmed as a causal factor through Mendelian randomization analysis.In summary,our research identified the proteomic signatures associated with the onset of depression,highlighting its potential for early intervention and tailored therapeutic avenues.

关 键 词：Plasma proteins DEPRESSION Brain structure 

分 类 号：R74[医药卫生—神经病学与精神病学]