MIFEPRISTONE AFTER TRAUMA TO ENHANCE RESILIENCE (MATTER)

创伤后米非司酮增强恢复力（物质）

• 批准号: 7953718
• 负责人: ANTONIA S NEW
• 金额: $ 0.17万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-03-01 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7953718
• 关键词: Animal Model; Animals; Anxiety Disorders; Applications Grants; Arousal; Blood Pressure; Charge; Chronic; Clinical; Clinical Research; Clinical Trials; Computer Retrieval of Information on Scientific Projects Database; Data; Development; Disease; Distress; Dose; Emotional; Etiology; Event; Exhibits; Exposure to; Extinction (Psychology); Functional disorder; Funding; Galvanic Skin Response; Goals; Grant; Heart Rate; Human; Individual; Institution; Intervention; Measures; Memory; Mental disorders; Mifepristone; Modeling; Pathway interactions; Patients; Pharmacological Treatment; Physiological; Play; Positioning Attribute; Post-Traumatic Stress Disorders; Process; Psychopathology; Research; Research Personnel; Resources; Role; Selective Serotonin Reuptake Inhibitor; Societies; Source; Stress; Suicide attempt; Symptoms; Testing; Therapeutic; Time; Trauma; United States National Institutes of Health; attenuation; base; clinical remission; conditioned fear; cost; design; effective therapy; improved; meetings; novel; novel therapeutic intervention; psychotic depression; 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. Specific hypotheses: Our primary objective is to determine if mifepristone is an effective treatment for the intrusive unwanted memories associated with PTSD when used in the context of reactivating a traumatic memory to interrupt reconsolidation of that memory. We believe that we are in a unique position to investigate novel therapeutic approaches based on memory reconsolidation disruption for the treatment of PTSD. The results from animal studies underway at Mount Sinai (In Dr. Cristina Alberini's lab) played a critical role in designing our clinical trial. Clinical Trial: Hypothesis 1: Mifepristone disrupts the reconsolidation of traumatic memories in an animal model, therefore, we will test whether mifepristone, which is a well tolerated in humans and have been extensively used in clinical settings as an abortofacient, and has been studied extensively in the treatment of psychotic depression, is effective in treating PTSD. We specifically predict that patients treated with two doses of mifepristone will show a greater decrease in subjective distress and less physiological arousal as measured by heart rate (HR), blood pressure (BP) and skin conductance (SC) while the listening to the trauma scripts one week later.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 该项目的主要目标是获取旨在为患有PTSD的人探索有效治疗的赠款提案的试点数据。 创伤后应激障碍（PTSD）是一种慢性和常见的焦虑症，暴露于压倒性的创伤事件之后。大多数PTSD患者也符合其他精神疾病的标准，许多人尝试自杀。尽管对社会的巨额成本，但对这种疾病的病因或病理生物生物学知之甚少。尽管PTSD对药理治疗（例如选择性5-羟色胺再摄取抑制剂（SSRIS））有些反应，但缓解率很少超过60％，甚至更少的患者（20-30％）可以实现临床缓解。一旦出现了心理病理学，PTSD通常与普遍和使人衰弱的症状有关，尽管有积极的治疗干预措施。因此，显然需要开发新颖和改善PTSD的治疗疗法。我们建议研究一种药理干预措施，旨在减少创伤的侵入性不良记忆，这通常是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mifepristone中断不需要的记忆的重新整合来做到这一点。我们的干预措施基于PTSD的恐惧调节模型，该模型考虑了侵入性，非自愿，重复性和生动的情感记忆，这是对PTSD发展的关键的创伤。这些记忆是健康个体和PTSD患者最初对创伤事件的最初反应的典型组成部分。 但是，对于健康的个体而言，随着时间的流逝，这些记忆的侵入性质量和情感指控往往会逐渐减少，而患有PTSD的个体不会表现出任何症状的衰减。持续创伤记忆的潜在原因可能是，在弱势群体中，创伤事件的记忆更加不可磨灭地编码，巩固和永久性地重新整合，这被认为抑制了健康个体中观察到的正常灭绝过程。 假设： 我们假设Mifepristone可能代表了一种药理治疗，该药理治疗与记忆重新激活与想象中的暴露相结合，可能会减轻PTSD的症状。 我们还假设，应力调节途径是为PTSD开发新疗法的易于获得和基本目标。因此，在这笔赠款中，我们建议使用与米非司酮给药的串联进行想象中的暴露对PTSD患者进行临床试验。 特定的假设： 我们的主要目的是确定米非司酮在使用创伤性记忆重新激活以中断该记忆重新溶解的情况下使用时，对与PTSD相关的侵入性不良内存的有效治疗方法。我们认为，我们处于一个独特的位置，可以根据记忆重新溶解中断PTSD来研究新颖的治疗方法。西奈山（Cristina Alberini's Lab博士）正在进行动物研究的结果在设计我们的临床试验中起着至关重要的作用。 临床试验： 假设1：米非司酮在动物模型中破坏了创伤性记忆的重新整合，因此，我们将测试在人类中耐受性良好的米非司酮是否在临床环境中广泛使用，作为一种流产型，并且已在精神抑郁症中进行了广泛的研究。我们明确地预测，用两剂米非酮治疗的患者在主观困扰中会显示出更大的减少，并且通过心率（HR），血压（BP）和皮肤电导（SC）测量的生理唤醒较少，而一周后听取创伤脚本的情况下。