Department of Cognitive Science, Budapest University of Technology and Economics, Budapest, Hungary; Nyírő Gyula Hospital - National Institute of Psychiatry and Addictions, Budapest, Hungary; Department of Physiology, Faculty of Medicine, University of Szeged, Szeged, Hungary.
Nyírő Gyula Hospital - National Institute of Psychiatry and Addictions, Budapest, Hungary.
Brain Behav Immun. 2017 May;62:256-264. doi: 10.1016/j.bbi.2016.12.011. Epub 2016 Dec 19.
Increasing evidence suggests that altered immune functions are related to the pathophysiology of schizophrenia. Relatively little information is available on Toll-like receptors (TLRs), which are implicated in the recognition of molecular patterns associated with pathogens and internal cellular damage signals. By using immunophenotyping and flow cytometry, we investigated TLRs in CD14+ monocytes, CD4+CD25+Foxp3+ regulatory T cells (T), and CD3+CD4+CD25+ activated T cells (T) in 35 drug-naïve patients with schizophrenia before and after an 8-week period of antipsychotic treatment with risperidone or olanzapine. As compared with 30 healthy control individuals, drug-naïve patients with schizophrenia exhibited an increased percentage of TLR4+ and TLR5+ monocytes and TLR5+ T/T cells. At the end of the treatment period, we observed normalized TLR4+ monocytes and an up-regulation of TLR2+ monocytes and T/T cells. Mean fluorescent intensity values, indicating receptor density, were consistent with these findings. In the drug-naïve state, but not after treatment, higher percentages of TLR4+ and TLR5+ monocytes were correlated with more severe cognitive deficits. Positive, negative, and general clinical symptoms were not associated with TLRs. There were no significant differences between patients receiving olanzapine and risperidone. These results indicate that abnormal expression of TLRs can be detected in the earliest stage of schizophrenia, which is modulated by antipsychotics. Immunological alterations in unmedicated schizophrenia patients may be linked to cognitive deficits.
越来越多的证据表明，免疫功能的改变与精神分裂症的病理生理学有关。关于 Toll 样受体（TLRs）的信息相对较少，TLRs 参与识别与病原体和细胞内损伤信号相关的分子模式。我们通过免疫表型和流式细胞术，研究了 35 例未经药物治疗的精神分裂症患者在接受利培酮或奥氮平 8 周抗精神病治疗前后 CD14+单核细胞、CD4+CD25+Foxp3+调节性 T 细胞（Treg）和 CD3+CD4+CD25+活化 T 细胞（T）中的 TLRs。与 30 名健康对照者相比，未经药物治疗的精神分裂症患者的 TLR4+和 TLR5+单核细胞以及 TLR5+T/T 细胞的比例增加。在治疗期末，我们观察到 TLR4+单核细胞正常化，以及 TLR2+单核细胞和 T/T 细胞的上调。表示受体密度的平均荧光强度值与这些发现一致。在未经药物治疗的状态下，但不是在治疗后，较高比例的 TLR4+和 TLR5+单核细胞与更严重的认知缺陷相关。TLRs 与阳性、阴性和一般临床症状无关。接受奥氮平和利培酮治疗的患者之间没有显著差异。这些结果表明，TLRs 的异常表达可以在精神分裂症的早期阶段检测到，并且可以被抗精神病药物调节。未经药物治疗的精神分裂症患者的免疫改变可能与认知缺陷有关。
