Circadian influence on fear extinction resulting from prolonged exposure therapy for PTSD

昼夜节律对 PTSD 长期暴露疗法引起的恐惧消退的影响

• 批准号: 10355111
• 负责人: Edward F. Pace-Schott
• 金额: $ 19.87万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-05-09 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10355111
• 关键词: Adopted; Aftercare; Age; Anxiety; Anxiety Disorders; Area Under Curve; Clinical; Clinical Trials; DSM-V; Development; Diagnosis; Disease; Disease remission; Distress; Electromyography; Extinction (Psychology); Face; Female; Fright; Galvanic Skin Response; Glucocorticoids; Healthcare; Healthcare Systems; Heart Rate; Home; Hour; Hydrocortisone; Imagery; Individual; Intake; Intervention; Investigational Therapies; Measures; Mediating; Memory; Mental Health Services; National Institute of Mental Health; Neurocognitive; Outcome; Outcome Measure; Panic; Panic Disorder; Participant; Physiology; Post-Traumatic Stress Disorders; Protocols documentation; Psychophysiology; Questionnaires; Randomized; Randomized Clinical Trials; Reporting; Research; Research Personnel; Salivary; Sampling; Schedule; Severities; Sleep; Social Anxiety Disorder; Spiders; Symptoms; Testing; Time; Trauma; Treatment Efficacy; Treatment outcome; Wrist; actigraphy; analog; arm; base; circadian; clinical outcome measures; cognitive reappraisal; conditioned fear; design; diaries; fear memory; indexing; inter-individual variation; learning extinction; male; prevent; reduce symptoms; response; sleep quality; social; therapy outcome; trial comparing

Fear extinction learning and memory are the neurocognitive bases of exposure therapies for anxiety- and trauma-related disorders, including prolonged exposure therapy (PE) for posttraumatic stress disorder (PTSD). Proposed research will examine time-of-day effects on extinction produced during PE for PTSD. Using an experimental paradigm in healthy individuals, we reported that extinction is better learned and generalized in the morning than evening. Our team also showed that exposure therapy for panic disorder is more efficacious when provided in the morning, and that higher endogenous cortisol levels mediate this effect. Thus a possible mechanism underlying this morning advantage is enhanced extinction learning by the morning circadian acrophase of endogenous cortisol. This Exploratory/Developmental mechanistic randomized clinical trial (RCT) will apply these findings to test the hypothesis that PE for PTSD delivered in the morning will show greater effects on fear memory extinction (target mechanism) and PTSD symptoms (clinical outcome), compared to PE delivered in the late afternoon. PE is an established, efficacious, manualized 10-session treatment. This RCT will compare 20 individuals treated with PE beginning within 2 hours of awakening (i.e., between 07:00- 10:00) to 20 treated at 16:00 or later. Participants will complete at-home exposures at the same time of day as PE sessions. Fear memory extinction, the primary mechanistic outcome, will be measured using a validated composite index for psychophysiological reactivity to trauma recall during script-driven imagery (SDI-PR). SDI- PR combines skin conductance, heart rate, and facial electromyography measures. The primary clinical outcome will be PTSD severity on the Clinician-Administered PTSD Scale (CAPS-5). SDI and CAPS-5 will occur at pre-, mid-, and post-treatment. Secondary mechanistic (peak subjective units of distress; SUDS) and clinical (PTSD Checklist for DSM-5) measures will be obtained at each PE session. Extinction learning will be operationalized as decreased SDI-PR across the 3 assessment time points and decreased SUDS across the 8 PE sessions that include imaginal exposure. Endogenous salivary cortisol levels, obtained immediately before each PE session and normalized using diurnal cortisol profiles, will be tested as a mechanism contributing to time of day effects on mechanistic and clinical outcome measures. Sleep quality will be assessed using wrist actigraphy and daily sleep diaries throughout treatment. We hypothesize that: (1) Morning, compared to late- afternoon, PE sessions will produce greater declines in mechanistic and clinical outcomes. (2) Higher cortisol levels measured at the previous PE session will be associated with greater session-to-session change in secondary mechanistic and clinical outcomes. (3) Better sleep quality will be associated with greater declines in mechanistic and clinical outcomes. Confirmation of hypotheses would suggest adopting strategic scheduling of PE to maximize clinical outcome, an easily implemented and inexpensive health care strategy.

恐惧消退学习和记忆是焦虑暴露疗法的神经认知基础， 创伤相关疾病，包括创伤后应激障碍（PTSD）的长期暴露疗法（PE）。 拟议的研究将检查体育治疗创伤后应激障碍期间对消退产生的时间影响。使用 在健康个体的实验范式中，我们报告说，灭绝是更好地学习和推广， 早上比晚上。我们的研究小组还表明，暴露疗法治疗恐慌症更有效 当在早上提供时，更高的内源性皮质醇水平介导了这种效果。因此， 这种早晨优势背后的机制是早晨昼夜节律增强的灭绝学习 内源性皮质醇的高峰期。这项探索性/开发性机制随机临床试验（RCT） 我将应用这些发现来检验这一假设，即在早晨进行的创伤后应激障碍的PE将显示出更大的 对恐惧记忆消退（目标机制）和PTSD症状（临床结局）的影响，与 下午晚些时候送过来的。PE是一种成熟、有效、手动化的10次治疗。这 RCT将比较20名在觉醒后2小时内开始接受PE治疗的个体（即，07：00- 10：00）至16：00或之后接受治疗的20例。参与者将在一天中的同一时间完成在家暴露， 体育课。恐惧记忆消退，主要的机制性结局，将使用经验证的 脚本驱动想象过程中创伤回忆的心理生理反应综合指数（SDI-PR）。SDI- PR结合了皮肤电导、心率和面部肌电图测量。主要临床 结果将是临床医生管理的PTSD量表（CAPS-5）上的PTSD严重程度。SDI和CAPS-5将 发生在治疗前、治疗中和治疗后。次级机制（痛苦的主观单位峰值; SUDS）和 在每次PE会议上获得临床（DSM-5的PTSD检查表）测量结果。灭绝学习将是 在3个评估时间点的SDI-PR降低和8个评估时间点的SUDS降低 体育课包括形象展示。内源性唾液皮质醇水平，获得之前立即 每次PE会话，并使用昼夜皮质醇曲线进行标准化，将作为一种机制进行测试， 一天中的时间对机械和临床结果测量的影响。睡眠质量将通过手腕评估 在整个治疗过程中记录活动记录和每日睡眠日记。我们假设：（1）早晨，与晚- 下午，体育课将产生更大的下降机制和临床结果。(2)高皮质醇 在前一次PE会议上测量的水平将与更大的会话到会话的变化相关， 次要机制和临床结局。(3)睡眠质量越好， 机械和临床结果。假设的确认将建议采用战略调度 最大限度地提高临床效果，这是一种易于实施且价格低廉的医疗保健策略。