Extinction of Fear Memories with Glucocorticoids in Veterans with PTSD

摘要 很少有关于人类的系统研究集中于一次改变潜在的创伤记忆 创伤后应激障碍已经建立。拟议的项目是一项基于我们在动物模型上的工作的翻译研究 在创伤后应激障碍中，皮质酮增加了情景恐惧记忆的消退。研究设计是一种 88名OEF/OIF退伍军人参与的双盲随机对照临床试验 创伤后应激障碍。我们计划使用脚本成像技术，将多次恐惧记忆重新激活与口述配对 糖皮质激素或安慰剂。参与者将在干预后1、3和6个月进行跟踪调查，以测量 预期效果的长寿。结果测量将包括创伤后应激障碍症状严重程度、抑郁 症状严重程度和生理指标。 具体目标/假设： 目的1：研究创伤性记忆复活后糖皮质激素的应用效果。 患有战斗相关创伤后应激障碍的退伍军人的精神症状。 需要检验的具体假设： (A)在创伤性记忆重新激活后接受外源性糖皮质激素治疗的受试者将证明 与那些在一周后接受安慰剂治疗的人相比，一周后接受创伤后应激障碍和抑郁症状的人更少 创伤性记忆重新激活。 (B)糖皮质激素的减少效应将是累积的；也就是说，减少将持续存在，并在- 重新激活糖皮质激素的使用将进一步减轻症状。 (C)接受安慰剂治疗的受试者，创伤后应激障碍和抑郁症状的减少将持续1、3和6个月。 外源性糖皮质激素与那些接受安慰剂的受试者进行比较。 目的2：研究创伤性记忆复活后糖皮质激素的应用效果。 对退伍军人个人战斗记忆的生理反应。 (D)在创伤记忆重新激活后接受外源性糖皮质激素治疗的受试者将证明 一周后，与服用安慰剂的人相比，生理反应减弱 创伤性记忆重新激活。 (E)与心理措施一样，抑制生理措施将证明 随着时间的推移持续存在，并在随后的糖皮质激素重新激活后积累。

Abstract There are very few systematic studies on humans that focus on changing the underlying traumatic memory once PTSD has been established. The proposed project is a translational study based on our work with animal models of PTSD in which coricosterone augmented extinction of contextual fear memories. The study design is a double-blind randomized controlled clinical trial involving eighty-eight OEF/OIF veterans with combat-related PTSD. We plan to pair multiple fear memory reactivations, using a scripted imagery technique, with an oral glucocorticoid or placebo. Participants will be followed at 1, 3, and 6 months post intervention to measure the longevity of the expected effect. Outcome measures will include PTSD symptom severity, depression symptoms severity, and physiological measures. Specific Aims/Hypothesis: Aim 1: Examine the effects of glucocorticoid administration following traumatic memory reactivation on psychiatric symptoms in veterans with combat-related PTSD. Specific hypotheses to be tested: (A) Subjects who receive an exogenous glucocorticoid after traumatic memory reactivation will demonstrate fewer PTSD and depression symptoms one week later, compared to those who receive a placebo after traumatic memory reactivation. (B) The glucocorticoid reduction effects will be cumulative; that is, reduction will persist, and further post- reactivation glucocorticoid administration will further reduce symptoms. (C) Decreases in PTSD and depression symptoms will persist at 1, 3, and 6 months for subjects receiving an exogenous glucocorticoid compared to those subjects receiving placebo. Aim 2: Examine the effects of glucocorticoid administration following traumatic memory reactivation on physiological responses to veteran's personal combat memories. (D) Subjects who receive an exogenous glucocorticoid after traumatic memory reactivation will demonstrate decreased physiological responses one week later, compared to those who receive a placebo after traumatic memory reactivation. (E) As with the psychological measures, suppression of the physiological measures will demonstrate both persistence over time and accumulation with subsequent post-reactivation glucocorticoid administration.