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.

恐惧灭绝学习和记忆是暴露疗法的神经认知基础 与创伤相关的疾病，包括延长创伤后应激障碍（PTSD）的暴露疗法（PE）。 拟议的研究将检查对PTSD PE期间产生的灭绝的日期影响。使用一个 在健康个体中，我们报告说，灭绝是更好地学习和推广的 早晨比晚上。我们的团队还表明，恐慌症的暴露疗法更有效 当早晨提供时，较高的内源性皮质醇水平会介导这种作用。因此可能 今天早上优势的机制是晨昼夜的灭绝学习 内源性皮质醇的尖量。这项探索性/发育机械的随机临床试验（RCT） 将应用这些发现来检验以下假设：早上交付的PTSD PE将显示更大 对恐惧记忆灭绝（目标机制）和PTSD症状（临床结局）的影响 PE在下午晚些时候交付。 PE是一种既定，有效，手动的10条经验治疗方法。这 RCT将在觉醒后的2小时内开始将20个人与PE治疗的人进行比较（即07：00-之间 10:00）到16:00或更高版本的20次治疗。参与者将在一天中的同一时间与 PE会议。恐惧记忆灭绝是主要的机理结果，将使用经过验证的 脚本驱动图像（SDI-PR）期间对创伤的心理生理反应性的综合指数。 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PTSD量表（CAPS-5）上的PTSD严重程度。 SDI和CAPS-5将 发生在治疗前，中和治疗。次要机械（遇险的峰值主观单位； SUD）和 在每个PE会议上将获得临床（DSM-5的PTSD清单）措施。灭绝学习将是 在3个评估时间点中降低了SDI-PR，在8个评估时间点降低了SDI-PR 包括想象中暴露的PE会议。内源性唾液皮质醇水平，立即获得 每个PE会话并使用昼夜皮质醇轮廓进行标准化，将测试作为有助于的机制 一天中的时间对机械和临床结果指标的影响。睡眠质量将使用手腕评估 整个治疗过程中的动作法和每日睡眠日记。我们假设：（1）早上，与晚期相比 下午，PE会议将导致机械和临床结果下降。 （2）较高的皮质醇 在上一个PE会话中测量的级别将与更大的会话与会议变化有关 次要机械和临床结果。 （3）更好的睡眠质量将与更大的下降有关 在机械和临床结果中。假设的确认将表明采用战略计划 PE最大化临床结果，这是一种易于实施且廉价的医疗保健策略。