{"title":"遗传证据支持脑区容量和功能网络改变在重度抑郁症中的作用。","authors":"Ming-Min Xu, Nan Li, Yi-Wen Lv, Wen-Miao Yang, Zhi-Yun Yu, Yi-Min Zhang, Yu Guo, Xiao-Yin Chen","doi":"10.1002/advs.202506032","DOIUrl":null,"url":null,"abstract":"<p>Despite emerging evidence of altered brain region volumes and functional networks in major depression (MD), causal relationships remain unexplored. Here, using genetic variants related to human brain morphometry (<i>n</i> = 36778) and functional networks (<i>n</i> = 47276), bidirectional two-sample and multivariable Mendelian randomization (MR) is performed to systematically investigate causal relationships between 83 brain-wide volumes, 191 resting-state functional magnetic resonance imaging phenotypes, and MD to identify core brain region volumes and functional networks associated with MD onset. Unlike other severe psychiatric disorders, reductions in left and right ventral diencephalon and thalamus volumes, together with decreased functional connectivity between the precuneus, cuneus, or cingulate gyri and frontal regions within the triple network (default mode network, central executive network, and salience network) uniquely predict MD onset. Using the identified markers as mediators in two-step MR recommends quitting smoking, moderately increasing alcohol frequency without developing alcohol use disorder, engaging in walking for leisure, and participating in exercises (e.g., swimming, cycling, keep fit, bowling) to positively influence imaging phenotypes and reduce MD risk. These findings enhance the understanding of predictive outcomes in brain imaging and support proactive prevention of severe mental health disorders through behavioral modifications.</p>","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":"12 37","pages":""},"PeriodicalIF":14.1000,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://advanced.onlinelibrary.wiley.com/doi/epdf/10.1002/advs.202506032","citationCount":"0","resultStr":"{\"title\":\"Genetic Evidence Supporting a Role for Brain Region Volume and Functional Network Alterations in Major Depression\",\"authors\":\"Ming-Min Xu, Nan Li, Yi-Wen Lv, Wen-Miao Yang, Zhi-Yun Yu, Yi-Min Zhang, Yu Guo, Xiao-Yin Chen\",\"doi\":\"10.1002/advs.202506032\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>Despite emerging evidence of altered brain region volumes and functional networks in major depression (MD), causal relationships remain unexplored. Here, using genetic variants related to human brain morphometry (<i>n</i> = 36778) and functional networks (<i>n</i> = 47276), bidirectional two-sample and multivariable Mendelian randomization (MR) is performed to systematically investigate causal relationships between 83 brain-wide volumes, 191 resting-state functional magnetic resonance imaging phenotypes, and MD to identify core brain region volumes and functional networks associated with MD onset. Unlike other severe psychiatric disorders, reductions in left and right ventral diencephalon and thalamus volumes, together with decreased functional connectivity between the precuneus, cuneus, or cingulate gyri and frontal regions within the triple network (default mode network, central executive network, and salience network) uniquely predict MD onset. Using the identified markers as mediators in two-step MR recommends quitting smoking, moderately increasing alcohol frequency without developing alcohol use disorder, engaging in walking for leisure, and participating in exercises (e.g., swimming, cycling, keep fit, bowling) to positively influence imaging phenotypes and reduce MD risk. These findings enhance the understanding of predictive outcomes in brain imaging and support proactive prevention of severe mental health disorders through behavioral modifications.</p>\",\"PeriodicalId\":117,\"journal\":{\"name\":\"Advanced Science\",\"volume\":\"12 37\",\"pages\":\"\"},\"PeriodicalIF\":14.1000,\"publicationDate\":\"2025-07-11\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://advanced.onlinelibrary.wiley.com/doi/epdf/10.1002/advs.202506032\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Advanced Science\",\"FirstCategoryId\":\"88\",\"ListUrlMain\":\"https://advanced.onlinelibrary.wiley.com/doi/10.1002/advs.202506032\",\"RegionNum\":1,\"RegionCategory\":\"材料科学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, MULTIDISCIPLINARY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Advanced Science","FirstCategoryId":"88","ListUrlMain":"https://advanced.onlinelibrary.wiley.com/doi/10.1002/advs.202506032","RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
Genetic Evidence Supporting a Role for Brain Region Volume and Functional Network Alterations in Major Depression
Despite emerging evidence of altered brain region volumes and functional networks in major depression (MD), causal relationships remain unexplored. Here, using genetic variants related to human brain morphometry (n = 36778) and functional networks (n = 47276), bidirectional two-sample and multivariable Mendelian randomization (MR) is performed to systematically investigate causal relationships between 83 brain-wide volumes, 191 resting-state functional magnetic resonance imaging phenotypes, and MD to identify core brain region volumes and functional networks associated with MD onset. Unlike other severe psychiatric disorders, reductions in left and right ventral diencephalon and thalamus volumes, together with decreased functional connectivity between the precuneus, cuneus, or cingulate gyri and frontal regions within the triple network (default mode network, central executive network, and salience network) uniquely predict MD onset. Using the identified markers as mediators in two-step MR recommends quitting smoking, moderately increasing alcohol frequency without developing alcohol use disorder, engaging in walking for leisure, and participating in exercises (e.g., swimming, cycling, keep fit, bowling) to positively influence imaging phenotypes and reduce MD risk. These findings enhance the understanding of predictive outcomes in brain imaging and support proactive prevention of severe mental health disorders through behavioral modifications.
期刊介绍:
Advanced Science is a prestigious open access journal that focuses on interdisciplinary research in materials science, physics, chemistry, medical and life sciences, and engineering. The journal aims to promote cutting-edge research by employing a rigorous and impartial review process. It is committed to presenting research articles with the highest quality production standards, ensuring maximum accessibility of top scientific findings. With its vibrant and innovative publication platform, Advanced Science seeks to revolutionize the dissemination and organization of scientific knowledge.