{"title":"精神分裂症相关风险基因对脑功能网络和执行缺陷的影响：一项对精神分裂症和遗传高风险个体的研究。","authors":"Ting Sun, Yue Zhu, Pengfei Zhao, Wenhui Zhao, Linzi Liu, Lili Tang, Mengxue Li, Yixiao Xu, Pengshuo Wang, Yifan Zhang, Yuning Zhou, Yifang Zhou, Jujiao Kang, Xiaohong Gong, Fei Wang, Yanqing Tang","doi":"10.1017/S0033291725101177","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Schizophrenia (SCZ) and genetic high-risk (GHR) individuals exhibit deficits in brain functional networks and cognitive function, potentially impacted by SCZ risk genes. This study aims to delineate these impairments in SCZ and GHR individuals, and further explore how risk genes affect brain networks and executive function.</p><p><strong>Methods: </strong>A total sample size of 292 participants (100 SCZ, 68 GHR, and 124 healthy controls [HCs]) in the study. The Wisconsin Card Sorting Test (WCST) and resting-state functional magnetic resonance imaging (rs-fMRI) are utilized to evaluate executive function and brain network topology. SCZ-related polygenic risk scores (SCZ-PRS) were used to evaluate genetic risk levels. WCST and PRS were not applied to all participants.</p><p><strong>Results: </strong>Significant reductions in nodal efficiency and degree centrality (D<sub>nodal</sub>) were observed within the right median cingulate and paracingulate gyri (MCPG_R) in both SCZ and GHR groups, compared to HCs. There were significant correlations between SCZ-PRS, D<sub>nodal</sub> in MCPG_R, and WCST scores. Moreover, D<sub>nodal</sub> in MCPG_R completely mediated the relationship between SCZ-PRS and executive function. The enrichment analysis of these risk genes indicates their involvement in biological processes of signal transduction and synaptic transmission.</p><p><strong>Conclusions: </strong>This study highlights the pivotal role of impaired cingulate function in mediating the effects of genetic risks on executive deficits, offering new insights into the genetic-neuro-cognitive nexus in schizophrenia and potential targets for clinical interventions.</p>","PeriodicalId":20891,"journal":{"name":"Psychological Medicine","volume":"55 ","pages":"e240"},"PeriodicalIF":5.5000,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12404332/pdf/","citationCount":"0","resultStr":"{\"title\":\"Impact of schizophrenia-associated risk genes on brain functional networks and executive deficits: a study of individuals with schizophrenia and genetic high risk.\",\"authors\":\"Ting Sun, Yue Zhu, Pengfei Zhao, Wenhui Zhao, Linzi Liu, Lili Tang, Mengxue Li, Yixiao Xu, Pengshuo Wang, Yifan Zhang, Yuning Zhou, Yifang Zhou, Jujiao Kang, Xiaohong Gong, Fei Wang, Yanqing Tang\",\"doi\":\"10.1017/S0033291725101177\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Schizophrenia (SCZ) and genetic high-risk (GHR) individuals exhibit deficits in brain functional networks and cognitive function, potentially impacted by SCZ risk genes. This study aims to delineate these impairments in SCZ and GHR individuals, and further explore how risk genes affect brain networks and executive function.</p><p><strong>Methods: </strong>A total sample size of 292 participants (100 SCZ, 68 GHR, and 124 healthy controls [HCs]) in the study. The Wisconsin Card Sorting Test (WCST) and resting-state functional magnetic resonance imaging (rs-fMRI) are utilized to evaluate executive function and brain network topology. SCZ-related polygenic risk scores (SCZ-PRS) were used to evaluate genetic risk levels. WCST and PRS were not applied to all participants.</p><p><strong>Results: </strong>Significant reductions in nodal efficiency and degree centrality (D<sub>nodal</sub>) were observed within the right median cingulate and paracingulate gyri (MCPG_R) in both SCZ and GHR groups, compared to HCs. There were significant correlations between SCZ-PRS, D<sub>nodal</sub> in MCPG_R, and WCST scores. Moreover, D<sub>nodal</sub> in MCPG_R completely mediated the relationship between SCZ-PRS and executive function. The enrichment analysis of these risk genes indicates their involvement in biological processes of signal transduction and synaptic transmission.</p><p><strong>Conclusions: </strong>This study highlights the pivotal role of impaired cingulate function in mediating the effects of genetic risks on executive deficits, offering new insights into the genetic-neuro-cognitive nexus in schizophrenia and potential targets for clinical interventions.</p>\",\"PeriodicalId\":20891,\"journal\":{\"name\":\"Psychological Medicine\",\"volume\":\"55 \",\"pages\":\"e240\"},\"PeriodicalIF\":5.5000,\"publicationDate\":\"2025-08-20\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12404332/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Psychological Medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1017/S0033291725101177\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"PSYCHIATRY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Psychological Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1017/S0033291725101177","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PSYCHIATRY","Score":null,"Total":0}
Impact of schizophrenia-associated risk genes on brain functional networks and executive deficits: a study of individuals with schizophrenia and genetic high risk.
Background: Schizophrenia (SCZ) and genetic high-risk (GHR) individuals exhibit deficits in brain functional networks and cognitive function, potentially impacted by SCZ risk genes. This study aims to delineate these impairments in SCZ and GHR individuals, and further explore how risk genes affect brain networks and executive function.
Methods: A total sample size of 292 participants (100 SCZ, 68 GHR, and 124 healthy controls [HCs]) in the study. The Wisconsin Card Sorting Test (WCST) and resting-state functional magnetic resonance imaging (rs-fMRI) are utilized to evaluate executive function and brain network topology. SCZ-related polygenic risk scores (SCZ-PRS) were used to evaluate genetic risk levels. WCST and PRS were not applied to all participants.
Results: Significant reductions in nodal efficiency and degree centrality (Dnodal) were observed within the right median cingulate and paracingulate gyri (MCPG_R) in both SCZ and GHR groups, compared to HCs. There were significant correlations between SCZ-PRS, Dnodal in MCPG_R, and WCST scores. Moreover, Dnodal in MCPG_R completely mediated the relationship between SCZ-PRS and executive function. The enrichment analysis of these risk genes indicates their involvement in biological processes of signal transduction and synaptic transmission.
Conclusions: This study highlights the pivotal role of impaired cingulate function in mediating the effects of genetic risks on executive deficits, offering new insights into the genetic-neuro-cognitive nexus in schizophrenia and potential targets for clinical interventions.
期刊介绍：
Now in its fifth decade of publication, Psychological Medicine is a leading international journal in the fields of psychiatry, related aspects of psychology and basic sciences. From 2014, there are 16 issues a year, each featuring original articles reporting key research being undertaken worldwide, together with shorter editorials by distinguished scholars and an important book review section. The journal''s success is clearly demonstrated by a consistently high impact factor.
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