Sun Ting, Zhu Yue, Zhao Pengfei, Zhao Wenhui, Liu Linzi, Tang Lili, Li Mengxue, Xu Yixiao, Wang Pengshuo, Zhang Yifan, Zhou Yuning, Zhou Yifang, Kang Jujiao, Gong Xiaohong, Wang Fei, Tang Yanqing
Department of Psychiatry, https://ror.org/0202bj006Shengjing Hospital of China Medical University, Shenyang, Liaoning, China.
Early Intervention Unit, Department of Psychiatry, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
Psychol Med. 2025 Aug 20;55:e240. doi: 10.1017/S0033291725101177.
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.
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.
Significant reductions in nodal efficiency and degree centrality (D) 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 in MCPG_R, and WCST scores. Moreover, D 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.
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.
精神分裂症（SCZ）患者和遗传高危（GHR）个体在脑功能网络和认知功能方面存在缺陷，可能受到SCZ风险基因的影响。本研究旨在描绘SCZ和GHR个体中的这些损伤，并进一步探索风险基因如何影响脑网络和执行功能。
本研究共有292名参与者（100名SCZ患者、68名GHR个体和124名健康对照[HCs]）。采用威斯康星卡片分类测验（WCST）和静息态功能磁共振成像（rs-fMRI）来评估执行功能和脑网络拓扑结构。使用与SCZ相关的多基因风险评分（SCZ-PRS）来评估遗传风险水平。WCST和PRS并非应用于所有参与者。
与HCs相比，在SCZ组和GHR组中，右侧中央扣带回和旁扣带回（MCPG_R）内的节点效率和度中心性（D）均显著降低。SCZ-PRS、MCPG_R中的D与WCST评分之间存在显著相关性。此外，MCPG_R中的D完全介导了SCZ-PRS与执行功能之间的关系。对这些风险基因的富集分析表明它们参与了信号转导和突触传递的生物学过程。
本研究强调了扣带回功能受损在介导遗传风险对执行功能缺陷影响中的关键作用，为精神分裂症的遗传-神经-认知关系提供了新的见解以及临床干预的潜在靶点。
