Department of Radiology, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, China; West China-PUMC C.C. Chen Institute of Health, Sichuan University, Chengdu, Sichuan, China.
Key Lab of Intelligent Information Processing of Chinese Academy of Sciences, Institute of Computing Technology, Chinese Academy of Sciences, Beijing, China.
Brain Behav Immun. 2024 Jan;115:557-564. doi: 10.1016/j.bbi.2023.11.006. Epub 2023 Nov 14.
Accumulating evidence suggests that inflammatory dysregulation both in blood and the brain is implicated in the pathogenesis of schizophrenia. Alterations in peripheral cytokines are not evident in all patients and there may be discrete altered inflammatory subgroups in schizophrenia. Recent studies using a novel and in vivo free-water imaging to detect inflammatory processes, have shown increased free water in white matter in schizophrenia. However, no studies to date have investigated the free water alterations in different inflammatory subgroups in schizophrenia.
Forty-four patients with schizophrenia and 49 controls were recruited. The serum levels of interleukin-1 beta (IL-1β), IL-6, IL-10, and IL-12p70 were measured and used for cluster analysis with K-means and hierarchical algorithms. Diffusion tensor imaging (DTI) images were collected for all participants and voxel-wise free water and fractional anisotropy of tissue (FA-t) were compared between groups with Randomise running in FSL. Partial correlation analysis was employed to explore the association of the peripheral cytokine levels with free water.
We identified two statistically quantifiable discrete subgroups of patients based on the cluster analysis of cytokine measures. The peripheral levels of IL-1β (P < 0.001), IL-10 (P = 0.041), and IL-12p70 (P < 0.001) showed significant differences between the two different inflammatory subgroups. In the inflammatory subgroup with a predominantly higher IL-1β level, increased free water values in white matter were found mainly in the left posterior limb of the internal capsule, posterior corona radiata, and partly in the left sagittal stratum. These affected areas did not overlap with the regions that showed significant free water differences between patients and healthy controls. In the inflammatory subgroup with lower IL-1β levels, peripheral IL-1β was significantly associated with free water values in white matter while no such association was detected in the patient group.
Localized free water differences were demonstrated between the two identified inflammatory subgroups in our data, and free water appears to be a feasible in vivo neuroimaging biomarker guiding the target of inflammatory intervention and development of new therapeutic strategies in an individualized manner in schizophrenia.
越来越多的证据表明，血液和大脑中的炎症失调与精神分裂症的发病机制有关。并非所有患者的外周细胞因子都发生改变，精神分裂症中可能存在离散的炎症亚群。最近使用新型活体自由水成像来检测炎症过程的研究表明，精神分裂症患者的白质中自由水增加。然而，迄今为止尚无研究调查精神分裂症不同炎症亚群中的自由水变化。
招募了 44 名精神分裂症患者和 49 名对照者。测量了白细胞介素-1β（IL-1β）、IL-6、IL-10 和 IL-12p70 的血清水平，并使用 K-均值和层次算法进行聚类分析。对所有参与者采集扩散张量成像（DTI）图像，并使用 FSL 中的 Randomise 比较组间的自由水和组织各向异性分数（FA-t）。采用偏相关分析探讨外周细胞因子水平与自由水的相关性。
我们根据细胞因子测量的聚类分析确定了两组具有统计学意义的离散患者亚群。两组不同的炎症亚群之间，外周 IL-1β（P<0.001）、IL-10（P=0.041）和 IL-12p70（P<0.001）水平有显著差异。在以较高 IL-1β 水平为主的炎症亚群中，白质中的自由水值增加主要发生在左侧内囊后肢、后放射冠，部分发生在左侧矢状层。这些受影响的区域与患者与健康对照者之间的白质自由水差异区域不重叠。在 IL-1β 水平较低的炎症亚群中，外周 IL-1β 与白质中的自由水值显著相关，而在患者组中未检测到这种相关性。
在我们的数据中，两个已确定的炎症亚群之间显示出局部的自由水差异，并且自由水似乎是一种可行的活体神经影像学生物标志物，可指导炎症干预的靶点，并为精神分裂症患者提供个体化的新治疗策略。
