Neural mechanisms underlying the antidepressant effects of sleep deprivation

 描述(申请人提供)：尽管抗抑郁药物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，而且只对尝试这些治疗方法的一小部分患者有效。40%到60%的抑郁症患者在完全或部分睡眠剥夺(SD)一晚后，情绪会迅速而显著地改善。尽管SD的抗抑郁作用早在几十年前就已为人所知，但这种作用背后的神经机制尚未阐明。功能神经成像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，并更好地了解了受抑郁症和SD影响的神经网络。我们小组和其他人之前的抑郁症研究一直表明，在唤醒、情绪调节和自我参照处理方面存在大脑网络功能障碍。我们在健康对照组中的神经成像数据显示，SD可以改变这些相同网络的功能，而这些变化与抑郁症患者和对照组的情况相反。在这里，我们建议研究一组N=48名无抗抑郁药物的男性和女性患者，以及N=12名健康对照组，这些患者在SD前后没有情绪障碍史，以提供对SD抗抑郁作用的神经底物的机械性洞察。我们假设SD引起的与不同抑郁症状维度相关的多个大脑网络的并发功能活动和连接性改变，包括情绪调节、注意、唤醒、自我参照和奖励加工，将是SD快速和短暂抗抑郁作用的基础。使用ABA设计，多模式脑成像以及更传统的脑电(EEG)和神经行为测试数据将在正常睡眠后的基线、全SD期间的一晚以及使用实验室方案的恢复睡眠一晚后获得，在此期间，受试者将由训练有素的工作人员持续监测。一个由抑郁症、神经成像、睡眠和时间生物学方面的专业研究人员组成的跨学科团队将合作，使用最先进的方法来实施这个项目。该项目的结果不仅将阐明SD快速抗抑郁作用的神经机制，还将产生基于大脑的生物标记物来预测或监测个体对SD的反应，并可能成为药物和神经调节干预的新靶点。

 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.