Biomarkers of the Response to CBT for Insomnia in Major Depression

描述（由申请人提供）： 重度抑郁症（MDD）患者未经治疗的失眠会增加自杀、抗抑郁反应差和抑郁复发的风险。失眠症的认知行为疗法（CBT）已经确立了失眠症的疗效，在副作用和获益的持久性方面优于药物治疗，但起效较慢。然而，我们缺乏CBT反应的预测因子，这可能有助于最佳地指导失眠治疗的选择。这方面的一个关键障碍是对CBT治疗机制的理解有限，这可能为开发临床有用的反应预测因子提供基础。本申请提出了一项辅助研究，旨在通过评估失眠合并MDD患者对CBT反应的有希望的睡眠EEG和遗传生物标志物来解决这一需求。这项母研究是最近由NIH资助的III期临床试验，其目的是记录CBT增强了255名患有抑郁症的失眠症患者对抗抑郁药物的抑郁反应。这项拟议的研究将检验这一假设，即睡眠脑电图测量中反映的稳态和觉醒相关机制，受到一些关键遗传多态性的影响，在失眠症的睡眠障碍中发挥作用，并被CBT的成分所靶向。这将通过获得少量不会对母研究产生不利影响的措施来实现。最终，这项工作可以作为MDD背景下失眠症个体化治疗的最终发展的基础，这可以缩短痛苦和残疾的时间，并最大限度地减少使用睡眠药物治疗的患者数量，从而降低成本和副作用并改善长期结果。公共卫生相关性：对MDD患者进行快速有效的失眠治疗至关重要，以最大限度地减少痛苦，残疾，成本和自杀风险。通过评估对CBT治疗MDD失眠反应的潜在生物标志物，拟议的研究将提高我们对在这种情况下发生的睡眠障碍和CBT治疗效果中发挥作用的机制的理解。因此，拟议的研究可能导致新的失眠疗法，并最终可能导致增加抗抑郁治疗反应的速度和持久性的方法，从而导致许多MDD和失眠患者的生活有临床意义的改善。(End摘要）

DESCRIPTION (provided by applicant): Untreated insomnia in those with major depressive disorder (MDD) increases risks of suicide, poor antidepressant response, and depressive relapse. Cognitive-behavioral therapy for insomnia (CBT) has established insomnia efficacy with advantages in terms of side-effects and durability of benefit over medication therapies but has slower onset of effect. However, we lack predictors of the CBT response that might help to optimally guide the choice of insomnia therapy. A key impediment in this regard is limited understanding of the therapeutic mechanisms of CBT that could provide a basis for the development of clinically useful predictors of response. This application proposes an ancillary study which aims to address this need by evaluating promising sleep EEG and genetic biomarkers of the response to CBT in individuals with insomnia comorbid with MDD. The parent study, a recently NIH-funded Phase III clinical trial, has a distinct aim of documenting that CBT enhances the depression response to antidepressant medication in 255 men and women with insomnia comorbid with MDD. The proposed study will test the hypothesis that homeostatic and arousal-related mechanisms that are reflected in sleep EEG measures and are affected by a few key genetic polymorphisms play a role in sleep disturbance in insomnia and are targeted by the components of CBT. This will be achieved by obtaining a small number of measures that will not adversely affect the parent study. Ultimately, this work could serve as the basis for the eventual development of individualized treatment of insomnia when present in the context of MDD, which could shorten the period of suffering and disability and minimize the number of patients treated with sleep medications, thus decreasing costs and side-effects and improving long-term outcome. PUBLIC HEALTH RELEVANCE: The administration of rapid and effective treatment for insomnia in those with MDD is critical in order to minimize suffering, disability, costs, and suicide risk. By evaluating potential biomarkers of the response to CBT for insomnia in MDD, the proposed study will improve our understanding of the mechanisms that play a role in sleep disturbance occurring in this setting and in the therapeutic effects of CBT. As a result, the proposed study could lead to novel insomnia therapies and, ultimately, could lead to means to increase the speed and durability of the response to antidepressant therapy and thereby result in clinically meaningful improvement in the lives of many patients with MDD and insomnia. (End of Abstract)