Treatment Implications of Trauma Memory Modulation for PTSD & Alcohol Dependence

创伤记忆调节对 PTSD 的治疗意义

• 批准号: 7944190
• 负责人: Michael E Saladin
• 金额: $ 40.81万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7944190
• 关键词: Address; Adrenergic Agents; Adrenergic Antagonists; Aftercare; Alcohol consumption; Alcohol dependence; Alcoholic Beverages; Alcohols; Amylases; Anti-Anxiety Agents; Anxiety; Area; Arousal; Basic Science; Behavior; Behavioral; Center for Translational Science Activities; Clinical; Clinical Sciences; Clinical Trials; Comorbidity; Consumption; Crime; Cues; Dependence; Development; Disease; Distress; Double-Blind Method; Elements; Emotional; Emotions; Event; Exposure to; Fright; Future; Gold; Heart Rate; Human; Hydrocortisone; Imagery; Individual; Inpatients; Intervention; Investigation; Laboratories; Lead; Link; Literature; Measures; Mediating; Medical; Memory; Mental Health; Methodology; Motivation; Nature; Negative Reinforcements; Neurosciences; Outcome; Participant; Persons; Pharmaceutical Preparations; Pharmacological Treatment; Pharmacotherapy; Physiological; Placebos; Population; Post-Traumatic Stress Disorders; Prevention; Procedures; Process; Propranolol; RNA Interference; Randomized; Reporting; Research; Retrieval; Risk; Role; Salivary; Schedule; Self Medication; Severities; Smell Perception; Source; South Carolina; Staging; Stress; Substance Use Disorder; Symptoms; System; Testing; Therapeutic; Therapeutic Effect; Time; Translational Research; Trauma; Treatment outcome; Universities; Vision; adrenergic; alcohol craving; alcohol cue; alcohol exposure; alcohol misuse; alcoholism therapy; analog; attenuation; base; behavior change; biological adaptation to stress; craving; cue reactivity; drinking; drinking behavior; dual diagnosis; effective therapy; emotional distress; follow-up; indexing; innovation; member; memory process; memory recall; memory retrieval; psychosocial; response; treatment effect

DESCRIPTION (provided by applicant): This application, titled "Treatment Implications of Trauma Memory Modulation for PTSD & Alcohol Dependence", primarily addresses broad Challenge Area (15) Translational Science and specific Challenge Topic, 15-AA-104: PTSD and Alcohol Dependence; it secondarily addresses broad Challenge Area (01) Behavior, Behavioral Change, and Prevention and specific Challenge Topic, 01-AA-105: Mechanisms of Behavior Change. Introduction: The co-occurrence of posttraumatic stress disorder (PTSD) and alcohol dependence (AD) is one of the most frequently occurring and debilitating mental health comorbidities. Several perspectives on the nature of the relationship between these disorders have been forwarded and one of the most widely recognized conceptualizations holds that PTSD sufferers often use alcohol as a means of dampening the emotional distress associated with PTSD. Over time, the alcohol use escalates into AD. From a behavior analytic perspective, the mechanism of action for the development of pathological drinking is the escape or avoidance it provides from the emotional distress of PTSD. An important implication of this conceptual understanding of the PTSD and AD interrelationship is that effective treatment of PTSD should yield significant reductions in motivation to drink and drinking behavior. There is a developing clinical literature that supports this assumption and the present study will contribute further to it by examining the impact of the ¿-adrenergic blocker propranolol on emotional distress, craving and other responses to trauma- and alcohol-related cues and on alcohol use and PTSD symptoms. The impetus for the proposed proof-of-concept translational research comes from both basic science and a developing clinical science literature that suggests the strategic administration of the ¿-adrenergic blocker propranolol after recalling the memory of a fear-inducing event(s) can result in an attenuation of the negative emotion and arousal of memories for the fear-inducing events. This effect is presumed to result from propranolol's ability to quell the adrenergic activity involved in the reconsolidation of memories for the fear-inducing event(s) after they are recalled. Approach: This study will employ 50 PTSD/AD comorbid participants to investigate the effects of propranolol vs. placebo, administered immediately after exposure to scripted imagery of a crime-related trauma, on the subjective, physiological and stress responses occurring during a subsequent test session consisting of exposure to the trauma scripted imagery and also the sight and smell of the participant's preferred alcoholic beverage. Participants will be randomly assigned to receive either 40 mg of propranolol or placebo (double-blinded) immediately after the first of two trauma-imagery cue exposure sessions scheduled to occur on consecutive days of an inpatient stay at MUSC's Clinical and Translational Research Center (CTRC). The first session will serve as a retrieval session during which trauma script-imagery cue exposure will elicit retrieval and reconsolidation of memories of the participant's index trauma; the second session will be a test session to examine the potential modulatory role of propranolol on the reconsolidated memories putatively elicited during the retrieval session. It is posited that changes in craving, physiological and/or stress reactivity during the test session will reflect propranolol's effects on memory reconsolidation processes elicited by trauma cue exposure in the retrieval session. Measures of subjective craving, emotion, physiological arousal (e.g., heart rate) and stress (e.g., cortisol) reactivity will be obtained at baseline, during and after the trauma cue presentation in session 1 and the trauma and alcohol cue presentations in the test session. The durability of any observed treatment effects will be assessed in a follow-up laboratory session performed 14 days following discharge from the inpatient stay and which will be identical to the test session. Treatment effects on both alcohol use during preceding 14 days and severity of PTSD symptoms will also be assessed. Implications: This research will directly address the challenge area of translational science in PTSD and AD by extending basic neuroscience findings on memory modulation to a human laboratory proof-of-concept analog with substantial potential clinical benefit for members of this at risk, dually afflicted population. Positive findings could energize future studies to define the optimal parameters under which propranolol could be used in prolonged exposure therapy (PTSD treatment gold standard) to enhance reduction of both PTSD-related anxiety and drinking. Additionally, the clinical benefits of cue exposure therapy for AD (i.e., systematic exposure to alcohol-related cues) might be enhanced by using propranolol to interfere with memory reconsolidation of the cue->alcohol associations that subserve craving for alcohol. In fact, both types of exposure therapy might be synergistically enhanced by strategic application of propranolol following retrieval of both trauma-memories and memories for cue->alcohol associations. The proposed research will also address the topic area of mechanisms of behavior change within the challenge area of behavior, behavioral change, and prevention by a) contributing to a literature base that suggests PTSD has a primary causal role in PTSD/AD comorbidity because PTSD is the source of the aversive emotion/arousal which, when dampened by alcohol use, provides the negative reinforcement that promotes further use and risk of dependence, and b) empirically assessing the role of the ¿-adrenergic system in the trauma-related memory processes that mediate the interface between PTSD and AD. This innovative translational research endeavor will employ an established cue reactivity/exposure methodology to assess the therapeutic potential of an untested and potentially promising adjunctive pharmacotherapy for one of the most prevalent and intractable mental health comorbidities, PTSD and alcohol dependence. It is hoped the results of this proof-of-concept investigation will lead to the development of a pharmacological treatment element that will enhance the outcomes of exposure-based treatment for individuals with PTSD and alcohol dependence and be generalizable to other co-occurring substance use disorders.

描述（由应用程序提供）：此应用，标题为“创伤和酒精依赖的创伤记忆调制的治疗含义”，主要地址为广泛的挑战领域（15）转化科学和特定挑战主题，15-AA-104：PTSD和酒精依赖；它的次要解决了广泛的挑战领域（01）行为，行为改变以及预防和特定挑战主题，01-AA-105：行为改变的机制。简介：创伤后应激障碍（PTSD）和酒精依赖性（AD）的共发生是最常见和令人衰弱的心理健康合并症之一。关于这些疾病之间关系性质的几种观点已经转发，并且最广泛认可的概念之一认为，PTSD患者经常使用酒精作为抑制与PTSD相关的情绪困扰的一种手段。随着时间的流逝，饮酒会升级为AD。从行为分析的角度来看，病理饮酒的开发作用机理是它从PTSD的情绪困扰中提供的逃避或回避。这种对PTSD和AD相互关系的概念理解的重要含义是，对PTSD的有效治疗应大大减少饮酒和饮酒行为的动机。有一种正在发展的临床文献支持这一假设，本研究将通过检查 - 肾上腺肾上腺素阻滞剂对情绪困扰，渴望以及对与创伤和酒精相关的提示以及对酒精使用和PTSD症状的影响，进一步贡献它。拟议的概念验证转化研究的动力来自基础科学和正在发展的临床科学文献，这表明在回忆起恐惧引起的事件的记忆后，对 - 肾上腺素能阻止剂普萘洛尔的战略管理可能导致恐惧感会导致的负面情绪和唤起恐惧引起的事件的记忆力。这种作用是由于普罗诺洛尔在召回恐惧引起的事件中重新整合记忆中涉及的肾上腺素能活性的能力而产生的。方法：这项研究将采用50名PTSD/AD合并参与者来研究普萘洛尔与安慰剂的影响，在暴露于与犯罪相关的创伤的脚本图像后立即进行管理，对随后的测试期间的主观，身体和压力反应发生在主观，身体和压力的反应中，这些测试的接触量是Treama脚本脚本脚本的图像和观众的味道，以及与众不同的味道，并享受了味道的味道，并闻到了奇特的早餐。在安排在MUSC临床和翻译研究中心（CTRC）住院住院期间，将随机分配参与者，以接收40 mg普萘洛尔或安慰剂（双盲）。第一届会议将作为检索会议，在此期间，创伤脚本象征提示暴露将引起参与者指数创伤的记忆的检索和重新整合；第二届会议将是一个测试会议，以检查普萘洛尔在检索会议期间被推迟引起的重新固定记忆的潜在调节作用。可以定位在测试期间的渴望，身体和/或压力反应性的变化将反映普罗诺洛尔对记忆重新溶解过程的影响，从而在检索期间通过创伤提示暴露引起。主观渴望，情感，身体唤醒（例如心率）和压力（例如皮质醇）反应性的度量将在基线，期间和之后的创伤提示表现以及在测试期间的创伤和饮酒表现中获得。任何观察到的治疗效果的耐用性将在从住院住院停留后14天进行的后续实验室会议中进行评估，并且与测试会议相同。在14天期间对两种饮酒的治疗效果以及PTSD症状的严重程度也将得到评估。含义：这项研究将通过将记忆调制的基本神经科学发现扩展到人类实验室概念验证类似物中，直接应对PTSD中转化科学的挑战领域，并将其具有巨大潜在的临床益处对这种危险的人群，双重影响的人群，具有巨大的潜在临床益处。积极的发现可能会为未来的研究提供能量，以定义可在长期暴露疗法（PTSD治疗金标准）中使用普萘洛尔的最佳参数，以增强PTSD与PTSD相关的焦虑和饮酒的降低。此外，通过使用普萘洛尔干涉使提示 - >酒精关联的记忆重新溶解，可以增强提示AD的提示暴露疗法（即系统接触与酒精相关的提示）的临床益处。实际上，在检索创伤膜和记忆的提示 - >酒精关联后，两种类型的暴露疗法都可以通过战略应用普萘洛尔来协同增强。拟议的研究还将解决行为，行为改变和预防挑战领域内行为变化机制的主题领域。从经验上评估 - 肾上腺素系统在介导PTSD和AD之间界面的与创伤相关的记忆过程中的作用。这项创新的转化研究努力将采用已建立的提示反应性/暴露方法来评估未经测试和潜在的证明辅助药物治疗的治疗潜力，以最普遍，最棘手的心理健康合并症之一，PTSD和酒精依赖性。希望这项概念证明调查的结果将导致药物治疗元素的发展，该治疗元素将增强针对PTSD和酒精依赖人群的基于暴露的治疗结果，并可以推广到其他同时发生的药物使用障碍。