Managing Sleep Symptoms and Modifying Mechanisms of Traumatic Stress

描述（由申请人提供）：创伤后应激障碍（PTSD），发生在至少15-20%暴露于创伤事件的个体中，是一种慢性疾病，与多种负面身心健康后果的发展以及重度抑郁症（MDD）的共同发生有关。睡眠障碍，尤其是噩梦和失眠，在PTSD患者中很常见，但PTSD的标准治疗并不直接关注睡眠问题。也许因此，睡眠障碍是PTSD治疗和抑郁症治疗后最常见的残留症状之一。重要的是，失眠、抑郁和创伤后应激障碍的特征都是类似的生物失调，包括睡眠重要方面的改变（快速眼动睡眠和慢波睡眠）以及与健康和疾病相关的过程（应激系统反应和炎症过程）。在PTSD和MDD的背景下直接治疗睡眠是可行的，并且可以导致睡眠的稳健改善，尽管改善睡眠是否可以增强PTSD和MDD的结果仍有待确定。这项研究将招募并随机分配150名患有PTSD、MDD和失眠症的参与者。基线评估（T1）后，受试者将随机接受失眠认知行为治疗（CBTi），这是一种支持良好且高效的失眠治疗，或仅接受监测的对照条件。在第一个干预期之后，所有参与者将接受认知加工疗法，这是一种以创伤为中心的疗法，对创伤后应激障碍和抑郁症有已知的影响。该研究将测试CBTi是否以及如何（1）实现PTSD和MDD症状严重程度的改善，以及（2）导致对认知加工疗法后续治疗的反应增强。在PTSD特异性治疗之前用CBTi进行干预并纵向测量生物标志物，将允许测试睡眠改善对PTSD，抑郁症状，客观方面睡眠和压力以及炎症标志物的特定影响，从而推进对PTSD和抑郁症中生物行为机制的基本理解。重要的是，所提出的方法利用了一种治疗序列，这种治疗序列可能会吸引具有创伤后事件症状的创伤幸存者，这些创伤幸存者可能对标准的PTSD治疗有抵抗力或没有准备好充分参与。研究假设的确认可以支持将研究结果立即转化为临床实践。

DESCRIPTION (provided by applicant): Posttraumatic Stress Disorder (PTSD), which occurs in at least 15-20% of individuals exposed to a traumatic event, is a chronic condition associated with the development of a multitude of negative physical and mental health consequences and the co-occurrence of Major Depressive Disorder (MDD). Sleep disturbances, and especially nightmares and insomnia, are quite common in patients with PTSD, but the standard treatments for PTSD do not directly focus on sleep problems. Perhaps as a result, sleep disturbances are one of the most common residual symptoms following both PTSD treatments and depression treatments. Importantly, insomnia, depression and PTSD are each characterized by similar biological dysregulation, including alterations in important aspects of sleep (rapid eye movement sleep and slow wave sleep) as well as processes linked to health and disease (stress system responses and inflammatory processes). Directly treating sleep in the context of PTSD and MDD is feasible and can lead to robust improvements in sleep, though whether improving sleep can enhance PTSD and MDD outcomes remains to be established. This study will enroll and randomize 150 participants with PTSD, MDD and insomnia. Following baseline assessments (T1) participants will be randomized to receive cognitive-behavioral therapy for insomnia (CBTi), a well-supported and highly effective insomnia treatment, or to a monitor only control condition. Following this first intervention period all participants will receive cognitive processing therapy a trauma-focused therapy with known effects on PTSD and depression. The study will test whether and how CBTi may (1) achieve improvements in PTSD and MDD symptom severity and (2) lead to enhanced response to subsequent treatment with cognitive processing therapy. Intervening with CBTi prior to a PTSD-specific treatment and measuring biomarkers longitudinally, will allow for the testing of specific effects of sleep improvement on PTSD, depressive symptoms, objective aspects sleep and stress and inflammatory markers, thereby advancing basic understanding of biobehavioral mechanisms in PTSD and depression. Importantly, the proposed approach utilizes a treatment sequence that may appeal to trauma survivors with post-traumatic event symptoms who may be resistant to or unprepared to fully engage in standard PTSD treatments. Confirmation of the study hypotheses could support immediate translation of the findings to clinical practice.