{"title":"抑郁症中健康、大脑结构和免疫代谢机制的社会决定因素:来自英国生物银行的多组学分析。","authors":"Huijie Xu , Zheng Zhang , Yanyue Ye , Jing Gu , Hui Chen , Zhengqian Jiang , Bohao Cheng , Huajia Tang , Sihong Li , Zheng Chang , Jiansong Zhou","doi":"10.1016/j.bbi.2025.106117","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Depression is a leading global health challenge, yet the role of Social Determinants of Health (SDH) in shaping depression risk − particularly through underlying biological mechanisms − remains insufficiently understood. This study leverages a multi-omics approach to explore how unfavorable social conditions influence depression through neural, and physiological pathways.</div></div><div><h3>Methods</h3><div>Drawing on data from 257,698 participants in the UK Biobank. Cox proportional hazards regression models were used to examine the relationship between SDH, polygenic risk scores (PRS), and depression. Correlation analyses were conducted to explore associations between SDH, biomarkers, brain structure, and depression. Two-sample mendelian randomization (MR) was applied to investigate causal relationships, while structural equation modeling (SEM) was used to examine interactions among SDH, depression, brain structure, PRS, and immune-metabolic biomarkers.</div></div><div><h3>Results</h3><div>Depression was significantly associated with SDH. Multivariable Cox regression showed that unfavorable SDH increased depression risk (HR = 1.916), and higher PRS was also linked to increased risk (HR = 1.288). The combination of unfavorable SDH and high PRS yielded the highest depression risk (HR = 2.578). MR analysis further emphasized the causal relationship between unfavorable SDH and depression. SDH was also linked to brain structural changes and metabolic markers, with smaller brain volumes in regions like the hippocampus and insula in the unfavorable SDH group, along with associations with biomarkers such as triglycerides and C-reactive protein. SEM analysis revealed that SDH influenced depression through immune-metabolic and brain structural pathways.</div></div><div><h3>Conclusions</h3><div>These findings underscore the multifaceted nature of depression, highlighting how social disadvantage becomes biologically embedded through genetic and physiological mechanisms. Addressing key modifiable components of SDH may represent a powerful strategy for targeted prevention, especially in genetically at-risk populations.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"130 ","pages":"Article 106117"},"PeriodicalIF":7.6000,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Social determinants of health, brain structure, and immune-metabolic mechanisms in depression: A multi-omic analysis from the UK Biobank\",\"authors\":\"Huijie Xu , Zheng Zhang , Yanyue Ye , Jing Gu , Hui Chen , Zhengqian Jiang , Bohao Cheng , Huajia Tang , Sihong Li , Zheng Chang , Jiansong Zhou\",\"doi\":\"10.1016/j.bbi.2025.106117\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><div>Depression is a leading global health challenge, yet the role of Social Determinants of Health (SDH) in shaping depression risk − particularly through underlying biological mechanisms − remains insufficiently understood. This study leverages a multi-omics approach to explore how unfavorable social conditions influence depression through neural, and physiological pathways.</div></div><div><h3>Methods</h3><div>Drawing on data from 257,698 participants in the UK Biobank. Cox proportional hazards regression models were used to examine the relationship between SDH, polygenic risk scores (PRS), and depression. Correlation analyses were conducted to explore associations between SDH, biomarkers, brain structure, and depression. Two-sample mendelian randomization (MR) was applied to investigate causal relationships, while structural equation modeling (SEM) was used to examine interactions among SDH, depression, brain structure, PRS, and immune-metabolic biomarkers.</div></div><div><h3>Results</h3><div>Depression was significantly associated with SDH. Multivariable Cox regression showed that unfavorable SDH increased depression risk (HR = 1.916), and higher PRS was also linked to increased risk (HR = 1.288). The combination of unfavorable SDH and high PRS yielded the highest depression risk (HR = 2.578). MR analysis further emphasized the causal relationship between unfavorable SDH and depression. SDH was also linked to brain structural changes and metabolic markers, with smaller brain volumes in regions like the hippocampus and insula in the unfavorable SDH group, along with associations with biomarkers such as triglycerides and C-reactive protein. SEM analysis revealed that SDH influenced depression through immune-metabolic and brain structural pathways.</div></div><div><h3>Conclusions</h3><div>These findings underscore the multifaceted nature of depression, highlighting how social disadvantage becomes biologically embedded through genetic and physiological mechanisms. Addressing key modifiable components of SDH may represent a powerful strategy for targeted prevention, especially in genetically at-risk populations.</div></div>\",\"PeriodicalId\":9199,\"journal\":{\"name\":\"Brain, Behavior, and Immunity\",\"volume\":\"130 \",\"pages\":\"Article 106117\"},\"PeriodicalIF\":7.6000,\"publicationDate\":\"2025-09-19\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Brain, Behavior, and Immunity\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0889159125003599\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Brain, Behavior, and Immunity","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0889159125003599","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
Social determinants of health, brain structure, and immune-metabolic mechanisms in depression: A multi-omic analysis from the UK Biobank
Background
Depression is a leading global health challenge, yet the role of Social Determinants of Health (SDH) in shaping depression risk − particularly through underlying biological mechanisms − remains insufficiently understood. This study leverages a multi-omics approach to explore how unfavorable social conditions influence depression through neural, and physiological pathways.
Methods
Drawing on data from 257,698 participants in the UK Biobank. Cox proportional hazards regression models were used to examine the relationship between SDH, polygenic risk scores (PRS), and depression. Correlation analyses were conducted to explore associations between SDH, biomarkers, brain structure, and depression. Two-sample mendelian randomization (MR) was applied to investigate causal relationships, while structural equation modeling (SEM) was used to examine interactions among SDH, depression, brain structure, PRS, and immune-metabolic biomarkers.
Results
Depression was significantly associated with SDH. Multivariable Cox regression showed that unfavorable SDH increased depression risk (HR = 1.916), and higher PRS was also linked to increased risk (HR = 1.288). The combination of unfavorable SDH and high PRS yielded the highest depression risk (HR = 2.578). MR analysis further emphasized the causal relationship between unfavorable SDH and depression. SDH was also linked to brain structural changes and metabolic markers, with smaller brain volumes in regions like the hippocampus and insula in the unfavorable SDH group, along with associations with biomarkers such as triglycerides and C-reactive protein. SEM analysis revealed that SDH influenced depression through immune-metabolic and brain structural pathways.
Conclusions
These findings underscore the multifaceted nature of depression, highlighting how social disadvantage becomes biologically embedded through genetic and physiological mechanisms. Addressing key modifiable components of SDH may represent a powerful strategy for targeted prevention, especially in genetically at-risk populations.
期刊介绍:
Established in 1987, Brain, Behavior, and Immunity proudly serves as the official journal of the Psychoneuroimmunology Research Society (PNIRS). This pioneering journal is dedicated to publishing peer-reviewed basic, experimental, and clinical studies that explore the intricate interactions among behavioral, neural, endocrine, and immune systems in both humans and animals.
As an international and interdisciplinary platform, Brain, Behavior, and Immunity focuses on original research spanning neuroscience, immunology, integrative physiology, behavioral biology, psychiatry, psychology, and clinical medicine. The journal is inclusive of research conducted at various levels, including molecular, cellular, social, and whole organism perspectives. With a commitment to efficiency, the journal facilitates online submission and review, ensuring timely publication of experimental results. Manuscripts typically undergo peer review and are returned to authors within 30 days of submission. It's worth noting that Brain, Behavior, and Immunity, published eight times a year, does not impose submission fees or page charges, fostering an open and accessible platform for scientific discourse.