Department of Psychiatry, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Department of Applied Mathematics and Statistics, Johns Hopkins University, Baltimore, MD, USA.
Brain Behav Immun. 2022 Feb;100:297-308. doi: 10.1016/j.bbi.2021.11.019. Epub 2021 Dec 4.
Peripheral inflammation is implicated in schizophrenia, however, not all individuals demonstrate inflammatory alterations. Recent studies identified inflammatory subtypes in chronic psychosis with high inflammation having worse cognitive performance and displaying neuroanatomical enlargement compared to low inflammation subtypes. It is unclear if inflammatory subtypes exist earlier in the disease course, thus, we aim to identify inflammatory subtypes in antipsychotic naïve First-Episode Schizophrenia (FES).
12 peripheral inflammatory markers, clinical, cognitive, and neuroanatomical measures were collected from a naturalistic study of antipsychotic-naïve FES patients. A combination of unsupervised principal component analysis and hierarchical clustering was used to categorize inflammatory subtypes from their cytokine data (17 FES High, 30 FES Low, and 33 healthy controls (HCs)). Linear regression analysis was used to assess subtype differences. Neuroanatomical correlations with clinical and cognitive measures were performed using partial Spearman correlations. Graph theoretical analyses were performed to assess global and local network properties across inflammatory subtypes.
The FES High group made up 36% of the FES group and demonstrated significantly greater levels of IL1β, IL6, IL8, and TNFα compared to FES Low, and higher levels of IL1β and IL8 compared to HCs. FES High had greater right parahippocampal, caudal anterior cingulate, and bank superior sulcus thicknesses compared to FES Low. Compared to HCs, FES Low showed smaller bilateral amygdala volumes and widespread cortical thickness. FES High and FES Low groups demonstrated less efficient topological organization compared to HCs. Individual cytokines and/or inflammatory signatures were positively associated with cognition and symptom measures.
Inflammatory subtypes are present in antipsychotic-naïve FES and are associated with inflammation-mediated cortical expansion. These findings support our previous findings in chronic psychosis and point towards a connection between inflammation and blood-brain barrier disruption. Thus, identifying inflammatory subtypes may provide a novel therapeutic avenue for biomarker-guided treatment involving anti-inflammatory medications.
外周炎症与精神分裂症有关，但并非所有个体都表现出炎症改变。最近的研究在慢性精神病中发现了炎症亚型，高炎症亚型的认知表现更差，且与低炎症亚型相比，其神经解剖学增大。目前尚不清楚炎症亚型是否在疾病早期就存在，因此，我们旨在鉴定抗精神病药物初治首发精神分裂症（FES）中的炎症亚型。
从抗精神病药物初治首发精神分裂症患者的自然史研究中收集了 12 种外周炎症标志物、临床、认知和神经解剖学指标。采用无监督主成分分析和层次聚类相结合的方法，根据细胞因子数据对炎症亚型进行分类（17 例 FES 高组、30 例 FES 低组和 33 例健康对照组（HCs））。采用线性回归分析评估亚型差异。采用偏Spearman 相关分析评估神经解剖学与临床和认知指标的相关性。采用图论分析评估炎症亚型间的全局和局部网络特性。
FES 高组占 FES 组的 36%，与 FES 低组相比，其 IL1β、IL6、IL8 和 TNFα 水平显著升高，与 HCs 相比，其 IL1β 和 IL8 水平也更高。与 FES 低组相比，FES 高组右侧海马旁回、后扣带回前部和上额下回的厚度更大。与 HCs 相比，FES 低组双侧杏仁核体积较小，皮质厚度广泛变薄。与 HCs 相比，FES 高组和 FES 低组的拓扑组织效率较低。单个细胞因子和/或炎症标志物与认知和症状测量值呈正相关。
在抗精神病药物初治首发精神分裂症中存在炎症亚型，与炎症介导的皮质扩张有关。这些发现支持我们在慢性精神病中的先前发现，并表明炎症与血脑屏障破坏之间存在联系。因此，鉴定炎症亚型可能为基于生物标志物的治疗提供新的治疗途径，包括使用抗炎药物。
