MIFEPRISTONE AFTER TRAUMA TO ENHANCE RESILIENCE (MATTER)

创伤后米非司酮增强恢复力（物质）

• 批准号: 7718208
• 负责人: ANTONIA S NEW
• 金额: $ 0.29万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-03-01 至 2009-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7718208
• 关键词: Anxiety Disorders; Applications Grants; Charge; Chronic; Clinical; Clinical Trials; Computer Retrieval of Information on Scientific Projects Database; Data; Development; Disease; Disease remission; Emotional; Etiology; Event; Exhibits; Exposure to; Extinction (Psychology); Functional disorder; Funding; Goals; Grant; Individual; Institution; Intervention; Memory; Mental disorders; Mifepristone; Modeling; Pathway interactions; Patients; Pharmacological Treatment; Post-Traumatic Stress Disorders; Process; Psychopathology; Rate; Research; Research Personnel; Resources; Selective Serotonin Reuptake Inhibitor; Societies; Source; Stress; Suicide attempt; Symptoms; Therapeutic; Thinking; Time; Trauma; United States National Institutes of Health; attenuation; base; conditioned fear; cost; improved; novel; resilience; response

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The principal goal of this project is to obtain pilot data for a grant proposal aimed at exploring effective treatments for individuals suffering from PTSD. Post-traumatic stress disorder (PTSD) is a chronic and common anxiety disorder that follows exposure to an overwhelming traumatic event. The majority of patients with PTSD also meet criteria for other psychiatric disorders and many attempt suicide. Despite its substantial costs to society, little is known about the etiology or pathophysiology of this disorder. While PTSD is somewhat responsive to pharmacological treatments such as selective serotonin reuptake inhibitors (SSRIs), response rates rarely exceed 60%, and even fewer patients (20-30%) achieve clinical remission. Once psychopathology emerges, PTSD is often associated with pervasive and debilitating symptoms that persist despite aggressive treatment interventions. Thus, there is a clear need to develop novel and improved therapeutics for PTSD. We propose to study a pharmacological intervention that aims to decrease the intrusive unwanted memories of the trauma, which are often the most severe and troubling component of PTSD symptoms. We propose to do this by using mifepristone to interrupt reconsolidation of the unwanted memories. Our intervention is based on the fear-conditioning model of PTSD that considers intrusive, involuntary, repetitive, and vivid emotionally-laden memories of a trauma as pivotal to the development of PTSD. Such memories are a typical component of the initial response to traumatic events in both healthy individuals and patients with PTSD. For healthy individuals, however, the intrusive quality and emotional charge of these memories tends to gradually diminish over time, whereas individuals with PTSD do not exhibit any attenuation in symptoms. One potential reason for the persistence of traumatic memories may be that in vulnerable individuals, memories of traumatic events are more indelibly encoded, consolidated, and perpetually reconsolidated, which is thought to inhibit the normal process of extinction observed in healthy individuals. Hypothesis: We hypothesize that mifepristone may represent a pharmacological treatment that, used in tandem with memory reactivation with imaginal exposure, may alleviate symptoms of PTSD. We also hypothesize that the stress modulatory pathway is an easily accessible and fundamental target for the development of new treatments for PTSD. Therefore, in this grant, we propose to conduct a clinical trials of PTSD patients using imaginal exposure in tandem with mifepristone administration.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 该项目的主要目标是获得一项拨款提案的试点数据，旨在探索针对患有创伤后应激障碍（PTSD）的个人的有效治疗方法。 创伤后应激障碍 (PTSD) 是一种慢性常见的焦虑症，发生于遭受压倒性的创伤事件后。大多数患有创伤后应激障碍的患者也符合其他精神疾病的标准，并且许多人试图自杀。尽管它给社会造成巨大损失，但人们对这种疾病的病因学或病理生理学知之甚少。虽然 PTSD 对选择性血清素再摄取抑制剂 (SSRI) 等药物治疗有一定的反应，但反应率很少超过 60%，达到临床缓解的患者甚至更少 (20-30%)。一旦出现精神病理学，创伤后应激障碍通常与普遍的、令人衰弱的症状相关，尽管采取了积极的治疗干预措施，这些症状仍然持续存在。因此，显然需要开发针对 PTSD 的新颖且改进的疗法。我们建议研究一种药物干预措施，旨在减少创伤的侵入性不良记忆，这些创伤往往是 PTSD 症状中最严重和最令人不安的组成部分。我们建议通过使用米非司酮来中断不需要的记忆的重新巩固来做到这一点。我们的干预基于 PTSD 的恐惧调节模型，该模型认为对创伤的侵入性、非自愿性、重复性和生动的、充满情感的记忆对于 PTSD 的发展至关重要。这种记忆是健康个体和创伤后应激障碍患者对创伤事件最初反应的典型组成部分。 然而，对于健康个体来说，这些记忆的侵入性和情感负担往往会随着时间的推移而逐渐减弱，而患有创伤后应激障碍的个体则不会表现出任何症状减弱。创伤记忆持续存在的一个潜在原因可能是，在脆弱个体中，创伤事件的记忆被更不可磨灭地编码、巩固和永久重新巩固，这被认为抑制了在健康个体中观察到的正常消退过程。 假设： 我们假设米非司酮可能代表一种药物治疗，与想象暴露的记忆重新激活一起使用，可以减轻 PTSD 的症状。 我们还假设压力调节途径是开发 PTSD 新疗法的一个容易获得的基本目标。因此，在这笔资助中，我们建议对 PTSD 患者进行一项临床试验，使用想象暴露与米非司酮给药相结合。