A Novel Use of a Sleep Intervention to Target the Emotion Regulation Brain Network and Treat Depression and Anxiety

项目总结/摘要 背景：有证据表明，失眠会导致情绪上的痛苦。 通过破坏调节情绪功能的大脑网络而产生抑郁情绪症状。的 特别值得关注的是，失眠与自杀风险增加有关，即使考虑到 存在其他抑郁症状。然而，我们还不知道在多大程度上， 调节大脑网络是通过睡眠的恢复来修改的，或者睡眠的程度是否 干预涉及这些神经靶点介导抑郁症状和自杀倾向的减少。 目的：本研究旨在探讨睡眠干预对情绪投入的影响 调节大脑网络作为一个假定的机制目标。设计/方法：在R61阶段， 机械试验将证明可行性，并确定情绪调节脑网络是否 当患者在经过证明的治疗后失眠症状有所改善时， 心理社会睡眠干预参与者将是70名经历抑郁症状加重的成年人， 临床意义上的失眠抑郁症状和失眠将在术前和每周进行评估， 在八周的时间内接受六次认知行为治疗（CBT-I）。CBT-I 通过睡眠限制，刺激控制，正念训练， 针对睡眠障碍信念的认知疗法，以及睡眠卫生教育。情绪调节 将在CBT-I治疗之前和之后测定网络神经靶标。如果Go里程碑 如果符合标准，R33期（3-5年）将包括一项2组随机对照试验。我们将招收新的 参与者（n=150），并将他们以1：1的比例随机分配到CBT-I或可信的对照治疗中， 失眠组。参与者将完成基于R61阶段研究的精确测量方案。 具体目标：R61的目标是证明（1）可行性和（2）CBT-I修改情绪调节 根据预先指定的Go里程碑标准来执行网络功能。R33的目标是（1）确认目标 通过测试假设，与主动控制条件相比，CBT-I参与者将 显示出情绪调节网络目标的显着变化，这些目标符合研究1的Go标准， 正常化方向，在治疗结束时，（2）检查目标接合与 研究组的治疗结果，以及（3）测试情绪调节网络是否在基线测量 预测抑郁症状和自杀倾向减少。影响：描述这些关联可能提供 有可能更深入地了解抑郁症的神经生物学机制， 失眠的存在。我们的研究结果将推进一种基于证据的机械治疗方法， 最终预防失眠带来的情绪困扰和潜在的生命威胁。

PROJECT SUMMARY/ABSTRACT Background: Several lines of evidence suggest that insomnia contributes to emotionally distressing depressive mood symptoms through disruption of brain networks that regulate emotional functions. Of particular concern, insomnia is associated with an increased risk for suicide, even when accounting for the presence of other depressive symptoms. However, we do not yet know to what degree that the emotion regulation brain network is modified by the restoration of sleep, or whether the degree to which a sleep intervention engages these neural targets mediates reductions in depressive symptoms and suicidality. Objective: This proposal investigates the impact of a proven sleep intervention on engagement of the emotion regulation brain network as a putative mechanistic target. DESIGN/METHODS: In the R61 phase, a mechanistic trial will demonstrate feasibility and establish whether the emotion regulation brain network is modified (the target is engaged) when patients show improvements in insomnia symptoms following a proven psychosocial sleep intervention. Participants will be 70 adults experiencing elevated depressive symptoms and clinically meaningful insomnia. Depressive symptoms and insomnia will be assessed prior to, and weekly while receiving six Cognitive Behavioral Therapy for Insomnia (CBT-I) sessions across a period of eight weeks. CBT-I improves sleep patterns through a combination of sleep restriction, stimulus control, mindfulness training, cognitive therapy targeting dysfunctional beliefs about sleep, and sleep hygiene education. Emotion regulation network neural targets will be assayed prior to and following completion of CBT-I treatment. If the Go milestone criteria are met, the R33 phase (years 3-5) will include a 2-arm randomized controlled trial. We will enroll new participants (n=150) and randomize them in a 1:1 ratio to the CBT-I or to the credible control treatment for insomnia group. Participants will complete a refined measurement protocol based on the R61 phase study. Specific aims: R61 aims are to demonstrate (1) feasibility and (2) that CBT-I modifies emotion regulation network function according to pre-specified Go milestone criteria. R33 aims are to (1) confirm target engagement by testing the hypothesis that compared with an active control condition, CBT-I participants will show significant change in the emotion regulation network targets that met the Go Criteria of Study 1 in the direction of normalization, at the end of treatment, (2) examine the relationships of target engagement to treatment outcomes by study group, and (3) test whether emotion regulation network measures at baseline predict depressive symptom and suicidality reduction. IMPACT: Characterizing these associations may offer the potential to gain a deeper understanding of the neurobiological mechanisms underlying depression in the presence of insomnia. Our results will advance an evidence-based mechanistic approach to treating, and ultimately preventing, the emotionally distressing and potentially life-threatening impact of insomnia.