Anxiety Disorders, Department of Psychiatry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Brain Behav Immun. 2013 May;30:12-21. doi: 10.1016/j.bbi.2012.08.015. Epub 2012 Sep 5.
Posttraumatic stress disorder (PTSD) is an anxiety disorder that may develop in response to a traumatic event. Approximately 10% of trauma-exposed individuals subsequently develop PTSD. It is hypothesized that the development of PTSD is associated with biological vulnerability factors, which are already present prior to the onset of symptoms. In this review we present an overview of currently identified vulnerability factors in the glucocorticoid (GC) signaling pathway for the development of PTSD. In addition, the implications of the identified vulnerability factors for potential preventive intervention strategies, including glucocorticoid receptor (GR) agonists and oxytocin, are discussed. Summarized, the findings of these studies indicate that individuals vulnerable for development of PTSD have dysregulations on various levels of the GC-signaling cascade: i.e. low levels of circulating levels of cortisol shortly after trauma, high GR number in peripheral blood mononuclear cells (PBMCs), high GILZ mRNA expression and low FKBP5 expression in PBMCs prior to trauma, and high sensitivity of T-cells for regulation by GCs prior to trauma. Furthermore, single nucleotide polymorphisms in the GR and FKBP5 genes have been found to be associated with increased risk for PTSD. Collectively, the identified vulnerability factors tentatively suggest that the development of PTSD may be preceded by a high sensitivity of various cells for regulation by GCs. The identification of these vulnerability factors may ultimately aid selective targeting of preventive interventions towards individuals at risk for PTSD. In addition, the identification of these vulnerability factors may eventually result in new preventive pharmacological strategies for PTSD.
创伤后应激障碍（PTSD）是一种焦虑障碍，可能是对创伤事件的反应而发展的。大约 10%的创伤暴露个体随后会发展出 PTSD。据推测，PTSD 的发展与生物脆弱性因素有关，这些因素在症状出现之前就已经存在。在这篇综述中，我们概述了目前在创伤后应激障碍发展的糖皮质激素（GC）信号通路中确定的脆弱性因素。此外，还讨论了已确定的脆弱性因素对潜在预防干预策略的影响，包括糖皮质激素受体（GR）激动剂和催产素。总的来说，这些研究的结果表明，易患 PTSD 的个体在 GC 信号级联的各个水平上存在失调：即创伤后短时间内循环皮质醇水平低、外周血单核细胞（PBMCs）中 GR 数量高、创伤前 PBMCs 中 GILZmRNA 表达高和 FKBP5 表达低，以及创伤前 T 细胞对 GC 调节的敏感性高。此外，还发现 GR 和 FKBP5 基因中的单核苷酸多态性与 PTSD 的风险增加有关。综上所述，这些确定的脆弱性因素表明，PTSD 的发展可能是各种细胞对 GC 调节的敏感性增加所致。这些脆弱性因素的确定可能最终有助于针对 PTSD 高危个体进行有针对性的预防干预。此外，这些脆弱性因素的确定最终可能会导致 PTSD 的新预防药理学策略。
