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精神分裂症患者免疫衰老相关T细胞表型、脑结构成像与认知障碍:一项有调节的中介分析

Immunosenescence-related T cell phenotypes, structural brain imaging, and cognitive impairment in patients with schizophrenia: a moderated mediation analysis.

作者信息

Li Na, Li Yanli, Yu Ting, Chen Wenjin, Gou Mengzhuang, Zheng Wenkai, Liu Zhaofan, Wang Xiaoying, Fang Jiao, Tong Jinghui, Chen Song, Tian Baopeng, Li Chiang-Shan R, Tian Li, Tan Yunlong

机构信息

Peking University HuiLongGuan Clinical Medical School, Beijing HuiLongGuan Hospital, Beijing, P. R. China.

School of Basic Medicine, Inner Mongolia Medical University, Hohhot, China.

出版信息

Schizophrenia (Heidelb). 2025 Jul 18;11(1):101. doi: 10.1038/s41537-025-00650-w.

Abstract

Cognitive impairment is a core characteristic of schizophrenia. Immunosenescence has been consistently implicated in the cognitive dysfunction observed in neurodegenerative diseases, but how it may relate to cognitive deficits in schizophrenia is still unclear. We explored the associations between immunosenescence and cognitive impairment in patients with schizophrenia (SCZ, n = 65) and healthy controls (HCs, n = 39). Immunosenescence markers were assessed by flow cytometry and included the percentage of naïve or memory T cell subsets labeled by CD4+/CD8+, CD45RA+(naïve)/CD45RO (memory), or CD95+(memory), as well as the intracellular levels of selected cytokines (IL-1β, IL-6, TNF-α, and IFN-γ) in T cell subsets. T1-weighted magnetic resonance imaging was performed to assess the subcortical volume and cortical thickness. Participants were evaluated using the Positive and Negative Syndrome Scale and the Chinese version of the MATRICS Consensus Cognitive Battery.The results indicated that (1) Compared with HCs, SCZ patients were characterized by fewer naïve and more memory T cell subsets, accompanied by altered intracellular cytokine levels, indicating immunosenescence phenotypes. (2) The intracellular IL-1β level in naïve CD8+CD45RA+CD95+ T cells was associated with working memory deficit in SCZ patients. (3) In a moderated mediation model, the effect of the IL-1β level on the working memory score was mediated by the thickness of the right inferior parietal lobule (IPL_R), and the volume of the right choroid plexus (CP) moderated the indirect pathway between the IL-1β level and IPL_R thickness. Our findings highlighted immunosenescence-related T cell phenotypes and the CP as potential biomarkers of cognitive deficit in SCZ.

摘要

认知障碍是精神分裂症的核心特征。免疫衰老一直被认为与神经退行性疾病中观察到的认知功能障碍有关,但它与精神分裂症认知缺陷之间的关系仍不清楚。我们探讨了精神分裂症患者(SCZ,n = 65)和健康对照者(HCs,n = 39)中免疫衰老与认知障碍之间的关联。通过流式细胞术评估免疫衰老标志物,包括用CD4+/CD8+、CD45RA+(初始)/CD45RO(记忆)或CD95+(记忆)标记的初始或记忆T细胞亚群的百分比,以及T细胞亚群中选定细胞因子(IL-1β、IL-6、TNF-α和IFN-γ)的细胞内水平。进行T1加权磁共振成像以评估皮质下体积和皮质厚度。使用阳性和阴性症状量表以及中文版的MATRICS共识认知成套测验对参与者进行评估。结果表明:(1)与HCs相比,SCZ患者的特征是初始T细胞亚群较少,记忆T细胞亚群较多,同时细胞内细胞因子水平改变,表明存在免疫衰老表型。(2)初始CD8+CD45RA+CD95+ T细胞中的细胞内IL-1β水平与SCZ患者的工作记忆缺陷相关。(3)在一个调节中介模型中,IL-1β水平对工作记忆分数的影响由右下顶叶(IPL_R)的厚度介导,右侧脉络丛(CP)的体积调节了IL-1β水平与IPL_R厚度之间的间接途径。我们的研究结果强调了免疫衰老相关的T细胞表型和CP作为SCZ认知缺陷的潜在生物标志物。

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