Laboratory of Neuroimmunology and Developmental Origins of Disease (NIDOD), University Medical Center Utrecht, Utrecht, The Netherlands.
Psychoneuroendocrinology. 2012 Nov;37(11):1822-36. doi: 10.1016/j.psyneuen.2012.03.018. Epub 2012 Apr 12.
Posttraumatic stress disorder (PTSD), major depressive disorder (MDD), and severe fatigue may develop in response to severe stress and trauma. These conditions have all been shown to be associated with altered sensitivity of leukocytes for regulation by glucocorticoids (GCs). However, it remains unknown whether sensitivity of leukocytes for GCs is a pre-existing vulnerability factor, or whether GC-sensitivity of leukocytes alters as a consequence of stress and stress-related conditions. Our aim was to investigate whether sensitivity of T-cells and monocytes for regulation by GCs (i.e. dexamethasone: DEX) assessed before military deployment predicts high levels of PTSD, depressive, and/or fatigue symptoms 6 months after return from deployment.
We included 526 male military personnel before deployment to Afghanistan. Logistic regression analysis was performed to predict fatigue, depressive, and PTSD symptoms 6 months after deployment based on sensitivity of LPS-induced TNF-α production and PHA-induced T-cell proliferation to DEX-inhibition before deployment.
Severe fatigue 6 months after deployment was independently associated with low DEX-sensitivity of monocyte TNF-α production before deployment. A high level of depressive symptoms after deployment was independently associated with a low DEX-sensitivity of T-cell proliferation. In contrast, a high level of PTSD symptoms after deployment was independently associated with a high DEX-sensitivity of T-cell proliferation before deployment, but only in individuals who reported PTSD symptoms without depressive symptoms. The predictive value of DEX-sensitivity was independent of childhood trauma and GR number, GR subtype and GR target gene mRNA expression in leukocytes.
We present here for the first time that the sensitivity of leukocytes for GCs prior to deployment is a predictive factor for the development of PTSD, depressive and fatigue symptomatology in response to deployment. Notably, PTSD, depressive and fatigue symptoms were differentially associated with GC-sensitivity of monocytes and T-cells and therefore may have different biological underpinnings.
创伤后应激障碍（PTSD）、重性抑郁障碍（MDD）和严重疲劳可能是对严重应激和创伤的反应。这些病症都已被证明与白细胞对糖皮质激素（GCs）调节的敏感性改变有关。然而，白细胞对 GCs 的敏感性是否是一种预先存在的易感性因素，或者白细胞对 GCs 的敏感性是否会因应激和应激相关状况而改变，仍不清楚。我们的目的是研究 T 细胞和单核细胞对 GCs（即地塞米松：DEX）调节的敏感性（即 LPS 诱导的 TNF-α 产生和 PHA 诱导的 T 细胞增殖对 DEX 抑制的敏感性），是否可预测从部署返回后 6 个月时的 PTSD、抑郁和/或疲劳症状的严重程度。
我们在部署到阿富汗之前纳入了 526 名男性军事人员。使用逻辑回归分析来预测部署后 6 个月时的疲劳、抑郁和 PTSD 症状，预测因子为部署前 LPS 诱导的 TNF-α 产生和 PHA 诱导的 T 细胞增殖对 DEX 抑制的敏感性。
部署后 6 个月时严重疲劳与部署前单核细胞 TNF-α 产生的 DEX 低敏感性独立相关。部署后出现高抑郁症状与 T 细胞增殖的 DEX 低敏感性独立相关。相比之下，部署后出现高 PTSD 症状与部署前 T 细胞增殖的 DEX 高敏感性独立相关，但仅在报告 PTSD 症状而无抑郁症状的个体中如此。DEX 敏感性的预测价值独立于童年创伤和白细胞中的 GR 数量、GR 亚型和 GR 靶基因 mRNA 表达。
我们在此首次提出，部署前白细胞对 GCs 的敏感性是 PTSD、抑郁和疲劳症状在部署后发生的预测因子。值得注意的是，PTSD、抑郁和疲劳症状与单核细胞和 T 细胞对 GCs 的敏感性不同相关，因此可能具有不同的生物学基础。
