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首发精神分裂症患者抗精神病药物治疗前后的细胞因子变化

Cytokine alterations in first-episode schizophrenia patients before and after antipsychotic treatment.

作者信息

de Witte Lot, Tomasik Jakub, Schwarz Emanuel, Guest Paul C, Rahmoune Hassan, Kahn René S, Bahn Sabine

机构信息

Department of Psychiatry, University of Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands.

Department of Chemical Engineering and Biotechnology, Tennis Court Road, Cambridge CB21QT, University of Cambridge, UK; Department of Neuroscience, Erasmus Medical Centre, Dr. Molewaterplein 50, 3015 GE, Rotterdam, The Netherlands.

出版信息

Schizophr Res. 2014 Apr;154(1-3):23-9. doi: 10.1016/j.schres.2014.02.005. Epub 2014 Feb 26.

Abstract

Schizophrenia has been associated with central nervous system and peripheral immune system imbalances. However, most studies have not yielded conclusive results due to limitations such as small sample size, dissimilarities in the clinical status of patients and the high variability of cytokine levels within the normal human population. Here, we have attempted to account for these limitations by carrying out standardised multiplex immunoassay analyses of 9 cytokines in serum from 180 antipsychotic-naïve first-episode schizophrenia patients and 350 matched controls across 5 clinical cohorts. All subjects were matched for potential confounding factors including age, gender, smoking and body mass index. We found that the levels of interleukin (IL)-1RA, IL-10 and IL-15 were increased significantly in patients across the cohorts. We also found that the levels of IL-1RA and IL-10 were decreased in 32 patients who had been followed up and treated for 6 weeks with atypical antipsychotics. Interestingly, we found that the changes in IL-10 levels were significantly correlated with the improvements in negative, general and total symptom scores. These results indicate that mixed pro- and anti-inflammatory responses may be altered in first onset patients, suggesting a role in the aetiology of schizophrenia. The finding that only the anti-inflammatory cytokine IL-10 responded to treatment in parallel with symptom improvement suggests that this could be used as a potential treatment response biomarker in future studies of schizophrenia.

摘要

精神分裂症与中枢神经系统和外周免疫系统失衡有关。然而,由于样本量小、患者临床状态差异以及正常人群中细胞因子水平的高变异性等限制,大多数研究尚未得出确凿结果。在此,我们试图通过对来自5个临床队列的180例未使用过抗精神病药物的首发精神分裂症患者和350例匹配对照的血清中的9种细胞因子进行标准化多重免疫分析来解决这些限制。所有受试者在年龄、性别、吸烟和体重指数等潜在混杂因素方面进行了匹配。我们发现,各队列患者中白细胞介素(IL)-1RA、IL-10和IL-15水平显著升高。我们还发现,32例接受非典型抗精神病药物治疗6周的患者中,IL-1RA和IL-10水平降低。有趣的是,我们发现IL-10水平的变化与阴性、总体和总症状评分的改善显著相关。这些结果表明,首发患者中促炎和抗炎反应的混合可能发生改变,提示其在精神分裂症病因学中的作用。仅抗炎细胞因子IL-10的水平变化与症状改善平行这一发现表明,在未来精神分裂症研究中,它可能作为潜在的治疗反应生物标志物。

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