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首发精神病患者的免疫和代谢改变。

Immune and metabolic alterations in first episode psychosis (FEP) patients.

机构信息

IRCCS Centro S. Giovanni di Dio, Fatebenefratelli, Brescia, Italy; Faculty of Psychology, eCampus University, Novedrate (Como), Italy.

IRCCS Centro S. Giovanni di Dio, Fatebenefratelli, Brescia, Italy.

出版信息

Brain Behav Immun. 2018 May;70:315-324. doi: 10.1016/j.bbi.2018.03.013. Epub 2018 Mar 13.

Abstract

The molecular underpinnings associated to first episode psychosis (FEP) remains to be elucidated, but compelling evidence supported an association of FEP with blood alterations in biomarkers related to immune system, growth factors and metabolism regulators. Many of these studies have not been already confirmed in larger samples or have not considered the FEP diagnostic subgroups. In order to identify biochemical signatures of FEP, the serum levels of the growth factors BDNF and VEGF, the immune regulators IL-1RA, IL-6, IL-10 and IL-17, RANTES/CCL5, MIP-1b/CCL4, IL-8 and the metabolic regulators C-peptide, ghrelin, GIP, GLP-1, glucagon, insulin, leptin, PAI-1, resistin and visfatin were analysed in 260 subjects collected in the GET UP project. The results indicated an increase of MIP-1b/CCL4, VEGF, IL-6 and PAI-1, while IL-17, ghrelin, glucagon and GLP-1 were decreased in the whole sample of FEP patients (p < 0.01 for all markers except for PAI-1 p < 0.05). No differences were evidenced for these markers among the diagnostic groups that constitute the FEP sample, whereas IL-8 is increased only in patients with a diagnosis of affective psychosis. The principal component analysis (PCA) and variable importance analysis (VIA) indicated that MIP-1b/CCL4, ghrelin, glucagon, VEGF and GLP-1 were the variables mostly altered in FEP patients. On the contrary, none of the analysed markers nor a combination of them can discriminate between FEP diagnostic subgroups. These data evidence a profile of immune and metabolic alterations in FEP patients, providing new information on the molecular mechanism associated to the psychosis onset for the development of preventive strategies and innovative treatment targets.

摘要

与首发精神病(FEP)相关的分子基础仍有待阐明,但有强有力的证据表明,FEP 与免疫系统相关的生物标志物、生长因子和代谢调节剂的血液改变有关。这些研究中的许多尚未在更大的样本中得到证实,或者没有考虑到 FEP 的诊断亚组。为了确定 FEP 的生化特征,分析了 260 名 GET UP 项目中采集的受试者的血清中脑源性神经营养因子(BDNF)和血管内皮生长因子(VEGF)、免疫调节剂白细胞介素-1受体拮抗剂(IL-1RA)、白细胞介素-6(IL-6)、白细胞介素-10(IL-10)、白细胞介素-17(IL-17)、调节蛋白趋化因子(RANTES)/CC 趋化因子配体 5(CCL5)、巨噬细胞炎性蛋白-1b/CC 趋化因子配体 4(MIP-1b/CCL4)、白细胞介素-8(IL-8)和代谢调节剂 C 肽、胃饥饿素、葡萄糖依赖性促胰岛素释放肽(GIP)、胰高血糖素样肽-1(GLP-1)、胰高血糖素、胰岛素、瘦素、纤溶酶原激活物抑制剂-1(PAI-1)、抵抗素和内脏脂肪素的水平。结果表明,整个 FEP 患者样本中 MIP-1b/CCL4、VEGF、IL-6 和 PAI-1 增加,而 IL-17、胃饥饿素、胰高血糖素和 GLP-1 减少(除 PAI-1 外,所有标志物均为 p<0.01,p<0.05)。在构成 FEP 样本的诊断组中,这些标志物没有差异,而 IL-8 仅在情感性精神病患者中增加。主成分分析(PCA)和变量重要性分析(VIA)表明,MIP-1b/CCL4、胃饥饿素、胰高血糖素、VEGF 和 GLP-1 是 FEP 患者中改变最大的变量。相反,没有一种分析标记物或它们的组合可以区分 FEP 的诊断亚组。这些数据表明 FEP 患者存在免疫和代谢改变的特征,为开发预防策略和创新治疗靶点提供了与精神病发病相关的分子机制的新信息。

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