Altered cellular immune reactivity in traumatized women with and without major depressive disorder

Altered cellular immune reactivity in traumatized women with and without major depressive disorder
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DOI:
10.1016/j.psyneuen.2018.10.023
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发表时间:
2019-03-01
影响因子:
3.7
通讯作者:
Wingenfeld, Katja
Wingenfeld, Katja
中科院分区:
医学2区
文献类型:
--
作者:
Hellmann-Regen, Julian;Spitzer, Carsten;Wingenfeld, Katja

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下丘脑-垂体-肾上腺(HPA)轴的改变,如糖皮质激素受体敏感性改变和免疫反应增强,可能参与了重度抑郁障碍(MDD)的发病。暴露于不良童年经历(ACE)会增加MDD的易感性,并可能与MDD的内分泌和免疫变化有关。为了弄清ACE和MDD的影响,我们招募了87名妇女:n=23名患有MDD和ACE的妇女,n=23名通过临床访谈和问卷(DSM-IV结构化临床访谈、早期创伤问卷、儿童创伤问卷)确定的MDD,n=24名没有ACE的MDD,n=21名没有目前或终生的MDD,n=26名健康妇女。体外分析外周血单核细胞中糖皮质激素信号转导和丝裂原刺激的增殖。此外,检测糖皮质激素和盐皮质激素受体(GR/MR)的mRNA表达。外周GR敏感性以及GR和MR的表达水平在组间没有显著差异。患有ACE的女性在有丝分裂原刺激后表现出增强的免疫反应,而不是MDD的存在。我们的结果提供了证据,证明有ACE病史的女性在细胞培养中的体外免疫反应发生了功能性改变。因此,血管紧张素转换酶可能通过炎症途径参与MDD的发病。
Alterations of the hypothalamic-pituitary-adrenal (HPA) axis such as altered glucocorticoid receptor sensitivity and increased immune reactivity might contribute to the pathogenesis of major depressive disorder (MDD). Exposure to adverse childhood experiences (ACE) precipitates vulnerability to MDD and might be associated with endocrine and immune alterations in the disorder.In order to disentangle the effects of ACE and MDD, we recruited 87 women: n = 23 with MDD and ACE as determined by clinical interview and questionnaires (Structured Clinical Interview for DSM-IV, Early Trauma Inventory, Childhood Trauma Questionnaire), n = 24 with MDD without ACE, n = 21 with ACE but no current or lifetime MDD, and n = 26 healthy women without either MDD or ACE. Glucocorticoid signaling and mitogen-stimulated proliferation were analyzed ex vivo in peripheral blood-derived mononuclear cells. Additionally, mRNA expression of the glucocorticoid and the mineralocorticoid receptor (GR / MR) was assessed.Peripheral GR sensitivity as well as GR and MR expression levels were not significantly different between groups. Women with ACE showed an increased immune response after mitogen stimulation independent of the presence of MDD.Our results provide evidence for a functionally altered ex-vivo immune response in cell cultures from women with a history of ACE. Thus, ACE might contribute to the pathogenesis of MDD through inflammatory pathways.