Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Department of Translational Neuroscience, University Medical Center Utrecht Brain Center, Utrecht University, Utrecht, the Netherlands.
Brain Behav Immun. 2023 Jul;111:334-342. doi: 10.1016/j.bbi.2023.04.019. Epub 2023 May 5.
Immune-related mechanisms have been suggested to be involved in schizophrenia. Various studies have shown changes in monocytes isolated from the blood of schizophrenia patients, including changes in monocyte numbers, as well as altered protein and transcript levels of important markers. However, validation of these findings and understanding how these results are related to immune-related changes in the brain and schizophrenia genetic risk factors, is limited. The goal of this study was to better understand changes observed in monocytes of patients with early-onset schizophrenia. Using RNA sequencing, we analyzed gene expression profiles of monocytes isolated from twenty patients with early-onset schizophrenia and seventeen healthy controls. We validated expression changes of 7 out of 29 genes that were differentially expressed in previous studies including TNFAIP3, DUSP2, and IL6. At a transcriptome-wide level, we found 99 differentially expressed genes. Effect sizes of differentially expressed genes were moderately correlated with differential expression in brain tissue (Pearson's r = 0.49). Upregulated genes were enriched for genes in NF-κB and LPS signaling pathways. Downregulated genes were enriched for glucocorticoid response pathways. These pathways have been implicated in schizophrenia before and play a role in regulating the activation of myeloid cells. Interestingly, they are also involved in several non-inflammatory processes in the central nervous system, such as neurogenesis and neurotransmission. Future studies are needed to better understand how dysregulation of the NF-κB and glucocorticoid pathways affects inflammatory and non-inflammatory processes in schizophrenia. The fact that dysregulation of these pathways is also seen in brain tissue, provides potential possibilities for biomarker development.
免疫相关机制被认为与精神分裂症有关。各种研究表明，精神分裂症患者血液中分离的单核细胞发生变化，包括单核细胞数量的变化，以及重要标志物的蛋白和转录水平的改变。然而，这些发现的验证以及理解这些结果与大脑中的免疫相关变化和精神分裂症遗传风险因素的关系，受到了限制。本研究的目的是更好地了解早发性精神分裂症患者单核细胞中观察到的变化。我们使用 RNA 测序分析了 20 例早发性精神分裂症患者和 17 例健康对照者分离的单核细胞的基因表达谱。我们验证了之前研究中 29 个差异表达基因中的 7 个基因的表达变化，包括 TNFAIP3、DUSP2 和 IL6。在全转录组水平上，我们发现了 99 个差异表达基因。差异表达基因的效应大小与脑组织中的差异表达中度相关（Pearson's r=0.49）。上调基因富集于 NF-κB 和 LPS 信号通路的基因。下调基因富集于糖皮质激素反应途径的基因。这些途径以前与精神分裂症有关，在调节髓样细胞的激活中起作用。有趣的是，它们还参与了中枢神经系统中的几个非炎症过程，如神经发生和神经传递。需要进一步的研究来更好地了解 NF-κB 和糖皮质激素途径的失调如何影响精神分裂症中的炎症和非炎症过程。这些途径在脑组织中也存在失调，这为生物标志物的开发提供了潜在的可能性。
