Neural mechanisms underlying the antidepressant effects of sleep deprivation

睡眠剥夺抗抑郁作用的神经机制

• 批准号: 9252590
• 负责人: Philip Richard Gehrman
• 金额: $ 62.51万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-04-01 至 2020-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9252590
• 关键词: Adult; Affect; Amygdaloid structure; Anterior; Antidepressive Agents; Arousal; Attention; Base of the Brain; Behavior assessment; Biological Markers; Biological Neural Networks; Brain; Brain imaging; Cerebrovascular Circulation; Chronobiology; Control Groups; Data; Development; Dimensions; Female; Functional disorder; Future; Individual; Intervention; Laboratories; Mental Depression; Mental disorders; Monitor; Mood Disorders; Moods; Outcome; Patients; Pharmacology; Prefrontal Cortex; Protocols documentation; Recording of previous events; Recovery; Research Personnel; Rest; Role; Sleep; Sleep Deprivation; Societies; Symptoms; Testing; Thalamic structure; Training; antidepressant effect; attentional bias; cingulate cortex; depressed patient; depressive symptoms; design; disability; disturbance in affect; effective intervention; emotion regulation; emotional stimulus; experience; insight; male; multimodality; neurobehavioral test; neuroimaging; neuromechanism; neuroregulation; novel; patient subsets; public health relevance; putamen; reduce symptoms; relating to nervous system; response; reward processing; support network; symptomatology

 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.

 描述（由申请人提供）：尽管抗抑郁治疗已经发展了数十年，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，并且仅对一小部分尝试这些干预措施的患者有效。 40% 至 60% 的抑郁症患者在一晚完全或部分睡眠剥夺 (SD) 后，情绪会得到快速而显着的改善。尽管 SD 的抗抑郁作用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。功能性神经影像学的最新进展为研究区域大脑功能的状态变化提供了新的机会，同时更好地了解受抑郁症和 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致证明，大脑网络存在唤醒、情绪调节和自我参照处理功能障碍。我们在健康对照组中的神经影像数据表明，SD 可以改变这些相同网络的功能，并且这些变化与抑郁症患者与对照组中观察到的变化相反。在这里，我们建议研究一组 N = 48 名未服用抗抑郁药物且目前有抑郁症状的男性和女性患者，以及 N = 12 名在 SD 前后没有情绪障碍病史的健康对照，以提供对 SD 抗抑郁作用背后的神经基质的机制见解。我们假设，SD 引起的多个大脑网络中与不同抑郁症状维度（包括情绪调节、注意力、唤醒、自我参照和奖励处理）相关的并发功能活动和连接变化，将是 SD 快速且短暂的抗抑郁作用的基础。使用 ABA 设计，将使用为期 5 天的实验室方案在正常睡眠后、一晚完全 SD 期间以及一晚恢复性睡眠后在基线处获取多模式脑成像以及更传统的脑电图 (EEG) 和神经行为测试数据，在此期间，受过训练的工作人员将持续监测受试者。一个由在抑郁症、神经影像学、睡眠和时间生物学方面拥有专业知识的跨学科研究人员团队将使用最先进的方法合作开展该项目。该项目的结果不仅将阐明 SD 快速抗抑郁作用背后的神经机制，还将产生基于大脑的生物标志物来预测或监测个体对 SD 的反应，以及药理学和神经调节干预的潜在新靶点。