Managing Sleep Symptoms and Modifying Mechanisms of Traumatic Stress

描述(申请人提供)：创伤后应激障碍(PTSD)至少发生在15%-20%的暴露于创伤事件的个人中，是一种与多种负面身心健康后果和严重抑郁障碍(MDD)并存的慢性疾病。睡眠障碍，尤其是噩梦和失眠，在创伤后应激障碍患者中相当常见，但创伤后应激障碍的标准治疗方法并不直接针对睡眠问题。也许结果是，睡眠障碍是创伤后应激障碍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都具有相似的生物失调的特征，包括睡眠的重要方面(快速眼动睡眠和慢波睡眠)以及与健康和疾病有关的过程(压力系统反应和炎症过程)的改变。在PTSD和MDD的背景下直接治疗睡眠是可行的，并可以导致睡眠的显著改善，尽管改善睡眠是否可以提高PTSD和MDD的结果仍有待确定。这项研究将招募150名患有创伤后应激障碍、MDD和失眠的参与者并将其随机分组。在基线评估(T1)之后，参与者将被随机分配到接受认知行为失眠治疗(CBTi)，这是一种得到良好支持和高效的失眠治疗方法，或者只接受监测的对照条件。在第一个干预期之后，所有参与者都将接受认知处理疗法，这是一种以创伤为重点的疗法，已知对创伤后应激障碍和抑郁症有效果。这项研究将测试CBTI是否以及如何可以(1)改善创伤后应激障碍和MDD症状严重程度，以及(2)导致对认知处理疗法后续治疗的增强反应。在针对创伤后应激障碍的治疗之前对CBTI进行干预并纵向测量生物标志物，将有助于测试睡眠改善对创伤后应激障碍、抑郁症状、客观方面的睡眠和压力以及炎症标志物的具体影响，从而促进对创伤后应激障碍和抑郁的生物行为机制的基本理解。重要的是，建议的方法利用了一种可能吸引具有创伤后事件症状的创伤幸存者的治疗序列，这些幸存者可能对标准的创伤后应激障碍治疗产生抵触或未做好充分准备。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。 公共卫生相关性：创伤后应激障碍(PTSD)和共生抑郁症与相当大的痛苦、健康差距和更高的医疗保健利用率有关。在某种程度上，在针对创伤后应激障碍的干预之前通过有针对性的干预来解决睡眠障碍，与单独治疗创伤后应激障碍相比，可以改善创伤后应激障碍和抑郁症状和/或缓解率，这将对现有的创伤后应激障碍治疗提供重要的补充。此外，由于在创伤后应激障碍和抑郁症中观察到的健康差异被认为部分是由内分泌和炎症调节失调所调节的，如果这些途径通过改善睡眠来改变，这最终可能对创伤后应激障碍人群的健康产生长期好处。

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. PUBLIC HEALTH RELEVANCE: Post-traumatic stress disorder (PTSD) and co-occurring depression are associated with considerable distress, health disparities, and increased health care utilization. To the extent that addressing sleep disturbance with a targeted intervention prior to a PTSD-specific intervention produces improvements in PTSD and depression symptoms and/or remission rates compared to PTSD treatment alone, this will provide an important complement to existing PTSD treatments. Further, since the health disparities observed in PTSD and depression are believed to be partially mediated by endocrine and inflammatory dysregulation, if these pathways are altered by improving sleep, this may ultimately have long term health benefits in PTSD populations.