Noto Cristiano, Ota Vanessa Kiyomi, Gouvea Eduardo S, Rizzo Lucas B, Spindola Leticia M N, Honda Pedro H S, Cordeiro Quirino, Belangero Sintia Iole, Bressan Rodrigo Affonseca, Gadelha Ary, Maes Michael, Brietzke Elisa
Department of Psychiatry, Universidade Federal de São Paulo, São Paulo, Brazil (Drs Noto, Rizzo, Cordeiro, Bressan, Gadelha, and Brietzke); First Episode Psychosis Program, Faculdade de Ciências Médicas da Santa Casa de São Paulo, São Paulo, Brazil (Drs Noto, Gouveia, Honda, and Cordeiro); Genetics Division, Department of Morphology and Genetics, Universidade Federal de Sao Paulo, São Paulo, Brazil (Drs Ota, Gouveia, Spindola, and Belangero); Department of Psychiatry, Deakin University, Geelong, Vic., Australia (Dr Maes); Department of Psychiatry, Chulalongkorn University, Bangkok, Thailand (Dr Maes).
Int J Neuropsychopharmacol. 2014 Oct 31;18(4):pyu042. doi: 10.1093/ijnp/pyu042.
There is robust evidence that schizophrenia is characterized by immune-inflammatory abnormalities, including variations on cytokine levels. The results of previous studies, however, are heterogeneous due to several confounding factors, such as the effects of antipsychotic drugs. Therefore, research on drug-naïve first-episode psychosis (FEP) patients is essential to elucidate the role of immune processes in that disorder.
The aim of this study is to compare cytokine levels (IL-2, IL-10, IL-4, IL-6, IFN-γ, TNF-α, and IL-17) in drug-naïve FEP patients both before and after treatment with risperidone for 10 weeks, and to investigate possible associations between cytokine levels and clinical responses to treatment and presence of depressive symptoms. It this study, we included 55 drug-naïve FEP patients who had repeated measurements of cytokine levels and 57 healthy controls.
We found that FEP patients had significantly higher IL-6, IL-10 and TNF-α levels than healthy controls. After risperidone treatment, these three cytokines and additionally IL-4 decreased significantly. No significant difference was found between the post-treatment cytokine levels in FEP patients and in healthy controls, suggesting that these alterations in cytokine profiles are a state marker of FEP. No significant association was found between risperidone-induced changes in cytokines and the clinical response to treatment or the presence of depression. There was a significant inverse association between the risperidone-induced changes in IL-10 and the negative symptoms.
In conclusion, our results show a specific cytokine profile in FEP patients (monocytic and regulatory T-cell activation) and suggest immunoregulatory effects of risperidone treatment, characterized by suppressant effects on monocytic, Th2, and T-regulatory functions.
有充分证据表明,精神分裂症的特征是免疫炎症异常,包括细胞因子水平的变化。然而,由于一些混杂因素,如抗精神病药物的影响,先前研究的结果并不一致。因此,对未使用过药物的首发精神病(FEP)患者进行研究对于阐明免疫过程在该疾病中的作用至关重要。
本研究的目的是比较未使用过药物的FEP患者在接受利培酮治疗10周前后的细胞因子水平(IL-2、IL-10、IL-4、IL-6、IFN-γ、TNF-α和IL-17),并研究细胞因子水平与治疗临床反应及抑郁症状存在之间的可能关联。在本研究中,我们纳入了55例未使用过药物的FEP患者,他们重复测量了细胞因子水平,以及57名健康对照者。
我们发现FEP患者的IL-6、IL-10和TNF-α水平显著高于健康对照者。利培酮治疗后,这三种细胞因子以及另外的IL-4显著下降。FEP患者治疗后的细胞因子水平与健康对照者之间未发现显著差异,这表明细胞因子谱的这些变化是FEP的一种状态标志物。利培酮引起的细胞因子变化与治疗临床反应或抑郁症状的存在之间未发现显著关联。利培酮引起的IL-10变化与阴性症状之间存在显著的负相关。
总之,我们的结果显示FEP患者存在特定的细胞因子谱(单核细胞和调节性T细胞激活),并提示利培酮治疗具有免疫调节作用,其特征是对单核细胞、Th2和T调节功能具有抑制作用。