Extinction of Fear Memories with Glucocorticoids in Veterans with PTSD

摘要 对人类的系统研究很少关注改变潜在的创伤记忆一次 创伤后应激障碍已经确立。该项目是基于我们的动物模型工作的转化研究 coricosterone增强了背景恐惧记忆的消退。研究设计是 一项双盲随机对照临床试验，涉及88名OEF/OIF退伍军人， 创伤后应激障碍我们计划将多种恐惧记忆的重新激活，使用脚本化的想象技术，与口头 糖皮质激素或安慰剂。将在干预后1、3和6个月对参与者进行随访，以测量 达到预期效果的寿命。结果测量将包括PTSD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：检查创伤记忆再激活后糖皮质激素给药对 退伍军人与战斗有关的创伤后应激障碍的精神症状。 待检验的具体假设： (A)创伤记忆重新激活后接受外源性糖皮质激素的受试者将证明 与那些在一周后接受安慰剂的人相比， 创伤记忆的重新激活 (B)糖皮质激素减少效应将是累积的;也就是说，减少将持续，并且进一步减少。 重新激活糖皮质激素的施用将进一步减轻症状。 (C)PTSD和抑郁症状的减少将持续1个月、3个月和6个月， 外源性糖皮质激素与接受安慰剂的受试者相比。 目的2：检查创伤记忆再激活后糖皮质激素给药对 对老兵个人战斗记忆的生理反应 (D)创伤记忆重新激活后接受外源性糖皮质激素的受试者将证明 一周后，与接受安慰剂的人相比， 创伤记忆的重新激活 (E)与心理措施一样，抑制生理措施将表明 随着时间的推移持续存在，并随着随后的再活化后糖皮质激素给药而积累。

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.