Inflammatory activation is associated with a reduced glucocorticoid receptor alpha/beta expression ratio in monocytes of inpatients with melancholic major depressive disorder.

Inflammatory activation is associated with a reduced glucocorticoid receptor alpha/beta expression ratio in monocytes of inpatients with melancholic major depressive disorder.
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炎症激活与忧郁症主要抑郁症的住院患者的单核细胞中糖皮质激素受体α/β表达比降低有关。

DOI:
10.1038/tp.2013.118
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发表时间:
2014-01-14
影响因子:
6.8
通讯作者:
Drexhage HA
Drexhage HA
中科院分区:
医学1区
文献类型:
--
作者:
Carvalho LA;Bergink V;Sumaski L;Wijkhuijs J;Hoogendijk WJ;Birkenhager TK;Drexhage HA

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在这项研究中,我们使用新技术来研究是否在抑郁症患者中发现循环单核细胞中炎症和其他免疫激活基因表达增强的连贯模式。由于单核细胞的高炎症状态可能与糖皮质激素抵抗有关,我们还包括糖皮质激素受体的两种亚型的基因。在这项研究中,我们的目的是在MDD患者的单核细胞中找到类似的炎症和免疫激活基因的一致模式,并招募了47名无药物治疗的MDD住院患者和42名健康对照。一个定量聚合酶链反应(Q-PCR)单核细胞基因表达分析进行了使用面板的炎症相关基因先前确定为异常调节情绪障碍患者。使用细胞计数珠阵列评估选定的血清细胞因子/趋化因子。采用汉密尔顿抑郁评分(HAMD)分析抑郁症状。与对照组相比,47个单核细胞炎症相关基因中有34个显著上调,2个显著下调,后者包括活性GRα基因,特别是在HAMD评分高的患者中。GRα表达的降低与单核细胞中炎性基因的上调密切相关。与对照组相比,患者血清IL 6、IL 8、CCL 2和VEGF水平显著升高。我们的数据表明,失调的两个相互关联的同源平衡系统,即免疫系统和糖皮质激素系统,共同发生在抑郁症。
In this study, we used new technology to investigate whether a coherent pattern of enhanced expression of inflammatory and other immune activation genes in circulating monocytes is found in patients with major depression. Since a high inflammatory state of monocytes might be related to glucocorticoid resistance, we also included the genes for the two isoforms of the glucocorticoid receptor. For this study, we aimed at finding a similar coherent pattern of inflammatory and immune activation genes in monocytes of patients with MDD and recruited 47 medication-free melancholic MDD inpatients and 42 healthy controls. A quantitative-polymerase chain reaction (Q-PCR) monocyte gene expression analysis was performed using a panel of inflammatory-related genes previously identified as abnormally regulated in mood disorder patients. Selected serum cytokines/chemokines were assessed using a cytometric bead array. Depressive symptoms were analysed using Hamilton depression scores (HAMD). Thirty-four of the 47 monocyte inflammatory-related genes were significantly upregulated and 2 were significantly downregulated as compared to controls, the latter including the gene for the active GRα in particular in those with a high HAMD score. The reduced GRα expression correlated strongly to the upregulation of the inflammatory genes in monocytes. Serum levels of IL6, IL8, CCL2 and VEGF were significantly increased in patients compared to controls. Our data show the deregulation of two interrelated homoeostatic systems, that is, the immune system and the glucocorticoid system, co-occurring in major depression.
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