Zhang Yan, Yuan Xiuxia, Zhang Yu, Chen Yishao, Su Keju, Xue Kangkang, Ding Suying, Chen Jingfeng, Fan Xiaoduo, Song Xueqin
Department of Psychiatry, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Biological Psychiatry International Joint Laboratory of Henan, Zhengzhou University, Zhengzhou, China.
BMC Psychiatry. 2025 May 7;25(1):462. doi: 10.1186/s12888-025-06905-1.
Studies have reported that white matter hyperintensities (WMHs) are associated with disturbances in immune function, and the relationship between WMHs and cognitive impairments have been documented in various clinical populations. The present study was to examine the relationship between WMHs, immune function, and cognitive impairments in patients with schizophrenia (SCH) remains unknown.
A sample of 127 drug-naïve first episode SCH and 72 healthy controls (HCs) were included in this study. Serum levels of cytokines and oxidative stress indices were measured using enzyme-linked immunosorbent assay and microtiter plate method. WMHs were assessed using T2-weighted magnetic resonance imaging scanning, and cognitive performance was evaluated using the MATRICS Consensus Cognitive Battery.
We found patients with SCH are more likely to present with WMHs compared with HCs (OR = 2.076, 95%CI 1.007-4.277, p = 0.048). SCH with WMHs displayed more pronounced cognitive deficits in domains including speed of processing, working memory, verbal learning, visual learning, reasoning, and problem-solving compared with patients without WMHs (p < 0.05). Correlation analysis showed that the volume of WMHs was negative correlated with the problem-solving score (r=-0.331, p = 0.042) in patients with SCH. Within the SCH group, patients with WMHs exhibited elevated levels of interleukin-2 (IL-2), reactive oxygen species (ROS), and superoxide dismutase (SOD), along with lower levels of serum interleukin-4 (IL-4) and interferon-γ (IFN-γ) compared with those without WMHs (p < 0.05). The mediation analyses demonstrated that serum levels of IFN-γ in SCH had fully indirect effects on cognitive function, mediated by the WMHs.
This study suggests that WMHs may play a vital mediating role in the relationship between inflammation, oxidative stress, and cognitive impairments in SCH. Future studies exploring the potential clinical utility of WMHs as biomarkers for early detection and intervention of SCH are warranted.
研究报告称，白质高信号（WMHs）与免疫功能紊乱有关，并且在各类临床人群中，WMHs与认知障碍之间的关系已有记载。然而，精神分裂症（SCH）患者中WMHs、免疫功能和认知障碍之间的关系仍不清楚。
本研究纳入了127例未服用过药物的首发SCH患者和72例健康对照（HCs）。采用酶联免疫吸附测定法和微量滴定板法测量细胞因子血清水平和氧化应激指标。使用T2加权磁共振成像扫描评估WMHs，并使用MATRICS共识认知成套测验评估认知表现。
我们发现，与HCs相比，SCH患者更易出现WMHs（OR = 2.076，95%CI 1.007 - 4.277，p = 0.048）。与无WMHs的患者相比，有WMHs的SCH患者在包括加工速度、工作记忆、言语学习、视觉学习、推理和问题解决等领域表现出更明显的认知缺陷（p < 0.05）。相关性分析表明，SCH患者中WMHs的体积与问题解决得分呈负相关（r = -0.331，p = 0.042）。在SCH组内，与无WMHs的患者相比，有WMHs的患者白细胞介素-2（IL-2）、活性氧（ROS）和超氧化物歧化酶（SOD）水平升高，同时血清白细胞介素-4（IL-4）和干扰素-γ（IFN-γ）水平降低（p < 0.05）。中介分析表明，SCH患者血清IFN-γ水平通过WMHs对认知功能具有完全间接效应。
本研究表明，WMHs可能在SCH的炎症、氧化应激和认知障碍之间的关系中起重要中介作用。未来有必要开展研究，探索WMHs作为SCH早期检测和干预生物标志物的潜在临床应用价值。
