Kovács Márton Áron, Tényi Tamás, Kugyelka Réka, Prenek Lilla, Hau Lídia, Magyar Éva Erzsébet, Herold Róbert, Balogh Péter, Simon Diána
Department of Psychiatry and Psychotherapy, Clinical Center, University of Pécs Medical School, Pécs, Hungary.
Department of Immunology and Biotechnology, Clinical Center, University of Pécs Medical School, Pécs, Hungary.
Front Psychiatry. 2020 Jan 23;10:996. doi: 10.3389/fpsyt.2019.00996. eCollection 2019.
Inflammation and immune dysregulation could contribute to the pathogenesis of schizophrenia. Osteopontin (OPN) is a cytokine-like glycoprotein involved in inflammation and in modulating immune responses, and it can also directly modify the cytokine expression and survival of microglia. Furthermore, elevated gene expression of OPN in first episode psychosis has recently been described, but to date OPN level has not been investigated in schizophrenia. Imbalance of T-helper subtypes could also represent a vulnerability factor for schizophrenia. In this study, we analyzed the concentration of OPN, levels of cytokines associated with T-helper subtypes: interferon gamma (IFNy) for Th1, interleukin (IL)-10 for Th2, IL-8 for Th17, and neutrophil-to-lymphocyte ratio (NLR) in 22 patients with schizophrenia assessed for the intensity of their symptoms by the Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression scale (CGI) scores. Serum OPN, IFNy, IL-10, and IL-8 concentrations were measured by ELISA kits and NLR was calculated from blood count. We found significant correlation between the level of OPN and PANSS-total and PANSS-general scores. IFNy level and NLR showed significant correlation with PANSS-total, PANSS-positive, PANSS-general, and CGI score. Among the measured markers antipsychotic therapy only had significant effects on NLR and OPN level, both of which were significantly reduced after long-term antipsychotic treatment. Our results indicate that elevated OPN and IFNy concentrations, and increased NLR are associated with severe symptoms in schizophrenia and suggest the importance of Th1 subtype in patients with high PANSS-positive and PANSS-general subscore. Significant correlation between NLR and PANSS scores strengthens the inflammation hypothesis of schizophrenia.
炎症和免疫失调可能在精神分裂症的发病机制中起作用。骨桥蛋白（OPN）是一种细胞因子样糖蛋白，参与炎症反应并调节免疫应答，它还能直接改变小胶质细胞的细胞因子表达和存活。此外，最近有研究描述了首发精神病患者中OPN基因表达升高，但迄今为止尚未对精神分裂症患者的OPN水平进行研究。辅助性T细胞亚型失衡也可能是精神分裂症的一个易患因素。在本研究中，我们分析了22例精神分裂症患者的OPN浓度、与辅助性T细胞亚型相关的细胞因子水平：Th1型的干扰素γ（IFNγ）、Th2型的白细胞介素（IL）-10、Th17型的IL-8，以及中性粒细胞与淋巴细胞比值（NLR），这些患者通过阳性和阴性症状量表（PANSS）和临床总体印象量表（CGI）评分评估症状严重程度。采用酶联免疫吸附测定试剂盒检测血清OPN、IFNγ、IL-10和IL-8浓度，并根据血常规计算NLR。我们发现OPN水平与PANSS总分和PANSS一般评分之间存在显著相关性。IFNγ水平和NLR与PANSS总分、PANSS阳性评分、PANSS一般评分和CGI评分均呈显著相关性。在所检测的标志物中，抗精神病治疗仅对NLR和OPN水平有显著影响，长期抗精神病治疗后两者均显著降低。我们的结果表明，OPN和IFNγ浓度升高以及NLR增加与精神分裂症的严重症状相关，并提示Th1亚型在PANSS阳性评分和PANSS一般评分较高的患者中的重要性。NLR与PANSS评分之间的显著相关性强化了精神分裂症的炎症假说。
