Neural mechanisms underlying the antidepressant effects of sleep deprivation

 描述（由申请人提供）：尽管抗抑郁治疗已经发展了几十年，但即使是最有效的干预措施也往往需要数周时间才能缓解症状，并且仅对尝试这些措施的一部分患者有效。40%至60%的抑郁症患者在一晚的完全或部分睡眠剥夺（SD）后情绪得到迅速而显著的改善。虽然SD的抗抑郁作用已经知道了几十年，但这种作用背后的神经机制尚未阐明。功能性神经影像学的最新进展为研究局部脑功能的状态变化提供了新的机会，沿着对抑郁症和SD影响的神经网络的更好理解。我们小组和其他人之前的抑郁症研究一直表明，唤醒、情绪调节和自我参照处理的大脑网络功能障碍。我们在健康对照组中的神经影像学数据显示，SD可以改变这些相同网络的功能，这些变化与抑郁症患者与对照组的变化相反。在这里，我们建议研究一组N=48无抗抑郁药的男性和女性患者，目前的抑郁症状和N=12健康对照组，没有历史的情绪障碍之前和之后SD提供机制洞察神经基板的抗抑郁作用。我们假设，SD诱导的并发功能活动和连接的变化，在多个大脑网络相关的不同抑郁症状的尺寸，包括情绪调节，注意力，唤醒，自我参照，奖励处理的基础上快速和短暂的抗抑郁作用的SD。使用阿坝设计，将在基线时正常睡眠后、一晚完全SD期间和一晚恢复睡眠后采集多模态脑成像沿着更传统的脑电图（EEG）和神经行为测试数据，使用5天实验室方案，在此期间受试者将由经过培训的工作人员持续监测。一个跨学科的研究团队，在抑郁症，神经成像，睡眠和时间生物学的专业知识将合作，使用国家的最先进的方法来执行这个项目。该项目的结果不仅将阐明SD快速抗抑郁作用的神经机制，而且还将产生基于大脑的生物标志物，以预测或监测SD的个体反应，以及药理学和神经调节干预的潜在新靶点。

 DESCRIPTION (provided by applicant): Despite decades of development of antidepressant treatments, even the most effective interventions often take weeks to achieve symptom relief, and are only effective in a subset of patients who try them. From 40 to 60% of patients with depression experience a rapid and significant improvement of mood with one night of total or partial sleep deprivation (SD). Although the antidepressant effect of SD has been known for decades, the neural mechanisms underlying this effect have not been elucidated. Recent advances in functional neuroimaging have provided new opportunities to investigate state changes in regional brain function, along with a better understanding of the neural networks affected by depression and SD. Previous depression studies from our group as well as others have consistently demonstrated dysfunction in brain networks underlying arousal, emotion regulation, and self-referential processing. Our neuroimaging data in healthy controls shows that SD can change the function of these same networks and these changes are opposite to that seen in depressed patients versus controls. Here we propose to study a group of N=48 antidepressant- free male and female patients with current depression symptom and N=12 healthy controls with no history of mood disorders before and after SD to provide mechanistic insight into the neural substrates underlying the antidepressant effects of SD. We hypothesize that SD-induced concurrent functional activity and connectivity changes in multiple brain networks related to different depressive symptom dimensions including emotion regulation, attention, arousal, self-referential, and reward processing will underlie the rapid and transient antidepressant effects of SD. Using an ABA design, multimodal brain imaging along with more traditional electroencephalographic (EEG) and neurobehavioral testing data will be acquired at baseline after normal sleep, during one night of total SD, and after one night of recovery sleep using a 5-day in laboratory protocol during which subjects will be continuously monitored by trained staff. An interdisciplinary team of researchers with expertise in depression, neuroimaging, sleep, and chronobiology will collaborate to carry out this project using state-of-the-art approaches. Results from this project will not only elucidate neural mechanisms underlying the rapid antidepressant effects of SD, but also yield brain-based biomarkers to predict or monitor individual responses to SD and potentially novel targets for pharmacological and neuromodulatory interventions.