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

项目摘要/摘要 背景：有几条证据表明失眠会造成情绪上的痛苦 通过破坏调节情绪功能的大脑网络而导致的抑郁情绪症状。的 尤其令人担忧的是，失眠与自杀风险的增加有关，即使在考虑到 存在其他抑郁症状。然而，我们还不知道这种情绪在多大程度上 大脑网络的调节是通过睡眠的恢复来调节的，或者睡眠的程度 通过干预这些神经靶点，可以减少抑郁症状和自杀倾向。 目的：本研究旨在探讨一种行之有效的睡眠干预对情绪投入的影响。 将脑网络作为一种假定的机械性靶点进行调控。设计/方法：在R61阶段， 机械性试验将论证可行性，并确定情绪调节脑网络是否 经证实的失眠症状改善后，患者的失眠症状得到改善。 心理社会睡眠干预。参与者将是70名患有高度抑郁症状的成年人和 临床上有意义的失眠。抑郁症状和失眠将在之前和每周进行评估 接受为期八周的六次失眠认知行为疗法(CBT-I)治疗。CBT-I 通过结合睡眠限制、刺激控制、正念训练、 针对睡眠功能障碍信念的认知疗法，以及睡眠卫生教育。情绪调节 网络神经靶点将在CBT-I治疗完成之前和之后进行检测。如果围棋的里程碑 如果符合标准，R33阶段(3-5年)将包括一项双臂随机对照试验。我们将招收新的 受试者(n=150)，并按1：1的比例随机将他们与CBT-I或 失眠组。参与者将在R61阶段研究的基础上完成改进的测量方案。 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 网络功能符合预先指定的GO里程碑标准。R33的目标是(1)确定目标 通过检验与主动控制条件相比，CBT-I参与者将 在符合研究1的GO标准的情绪调节网络目标方面显示出显著的变化 正常化方向，在治疗结束时，(2)检查目标接触与 根据研究组的治疗结果，以及(3)测试情绪调节网络是否在基线水平进行测量 预测抑郁症状和自杀率的降低。影响：描述这些关联可能会提供 更深入地了解抑郁症潜在的神经生物学机制的可能性 失眠的存在。我们的结果将推进一种基于证据的机械治疗方法，以及 最终防止失眠带来的情绪上的痛苦和潜在的生命威胁。

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.