Biomarkers of the Response to CBT for Insomnia in Major Depression

描述(由申请人提供)： 患有严重抑郁障碍(MDD)的人如果不接受治疗，失眠会增加自杀、抗抑郁药物反应差和抑郁复发的风险。认知行为疗法(CBT)已经确立了失眠的疗效，与药物疗法相比，在副作用和益处的持久性方面具有优势，但起效较慢。然而，我们缺乏CBT反应的预测指标，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治疗机制的有限了解，这可能为开发临床上有用的反应预测指标提供基础。这项申请提出了一项辅助研究，旨在通过评估有前景的睡眠脑电和CBT反应的遗传生物标记物来解决这一需求。这项母研究是最近由美国国立卫生研究院资助的第三阶段临床试验，其明确的目的是证明CBT在255名患有MDD的失眠患者中增强了抗抑郁药物的抑郁反应。这项拟议的研究将检验这一假设，即反映在睡眠脑电测量中并受几个关键基因多态影响的动态平衡和唤醒相关机制在失眠的睡眠障碍中发挥作用，并成为CBT成分的靶点。这将通过获得少量不会对家长研究产生不利影响的措施来实现。最终，这项工作可以作为最终开发MDD背景下的失眠个体化治疗的基础，这可以缩短痛苦和残疾的时间，最大限度地减少接受安眠药治疗的患者数量，从而降低成本和副作用，并改善长期结果。公共卫生相关性：对患有MDD的人实施快速有效的失眠治疗对于将痛苦、残疾、费用和自杀风险降至最低至关重要。通过评估CBT治疗MDD失眠的潜在生物标志物，拟议的研究将提高我们对在这种情况下发生睡眠障碍的机制以及CBT的治疗效果的理解。因此，这项拟议的研究可能导致新的失眠疗法，并最终可能导致提高抗抑郁药物治疗反应的速度和持久性的方法，从而对许多MDD和失眠患者的生活产生临床意义的改善。(摘要结束)

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)