Korhonen Laura, Paul Elisabeth R, Wåhlén Karin, Haring Liina, Vasar Eero, Vaheri Antti, Lindholm Dan
Center for Social and Affective Neuroscience, Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
Department of Biochemical and Clinical Sciences (BKV), Linköping University, Linköping, Sweden.
Transl Psychiatry. 2023 Oct 20;13(1):326. doi: 10.1038/s41398-023-02627-8.
Immune cells and cytokines are largely recognized as significant factors in the pathophysiology of neuropsychiatric disorders. The possible role of other blood cells such as leukocytes in events of acute psychosis is in contrast only emerging. To study blood-born markers in acute psychosis we here evaluated plasma proteins in drug-naive first-episode psychosis (FEP) patients and healthy controls using a multiplex proximity extension assay technique. We analyzed a panel of 92 immune markers and plasma samples from 60 FEP patients and 50 controls and evaluated the changes obtained using multivariate statistical methods followed by protein pathway analyses. Data showed that 11 proteins are significantly different between FEP patients and healthy controls We observed increases in pro-inflammatory proteins such as interleukin-6, oncostatin-M, and transforming growth factor-alpha in FEP patients compared with controls. Likewise, the extracellular newly identified RAGE-binding protein (EN-RAGE) that regulates the expression of various cytokines was also elevated in the plasma of FEP patients. The results indicate that neutrophil-derived EN-RAGE could play an important role during the early phase of acute psychosis by stimulating cytokines and the immune response targeting thereby likely also the brain vasculature.
免疫细胞和细胞因子在很大程度上被认为是神经精神疾病病理生理学中的重要因素。而其他血细胞如白细胞在急性精神病事件中的可能作用则刚刚开始显现。为了研究急性精神病中的血液标志物，我们在这里使用多重邻近延伸分析技术评估了未服用药物的首发精神病（FEP）患者和健康对照者的血浆蛋白。我们分析了一组92种免疫标志物以及来自60名FEP患者和50名对照者的血浆样本，并使用多变量统计方法评估所得到的变化，随后进行蛋白质通路分析。数据显示，FEP患者和健康对照者之间有11种蛋白质存在显著差异。我们观察到，与对照组相比，FEP患者中促炎蛋白如白细胞介素-6、抑瘤素-M和转化生长因子-α有所增加。同样，新发现的调节各种细胞因子表达的细胞外RAGE结合蛋白（EN-RAGE）在FEP患者的血浆中也有所升高。结果表明，中性粒细胞衍生的EN-RAGE可能通过刺激细胞因子和免疫反应，在急性精神病的早期阶段发挥重要作用，从而可能也靶向脑血管系统。
