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（由适用提供）：尽管发展了数十年的抗抑郁治疗，即使是最有效的干预措施也经常需要数周才能缓解症状，并且仅在尝试尝试治疗的患者中有效。从40％到60％的抑郁症患者经历了一晚或部分睡眠剥夺（SD）的快速和显着改善。尽管SD的抗抑郁作用已知数十年，但这种效果的中性机制尚未阐明。功能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，并更好地了解受抑郁症和SD影响的神经元网络。我们小组以及其他人的先前抑郁症研究一直表现出在唤醒，情绪调节和自指加工的脑网络中功能障碍。我们在健康对照中的神经影像学数据表明，SD可以改变这些网络的功能，这些变化与抑郁症患者与对照组相反。在这里，我们建议研究一组N = 48个抗抑郁药 - 无抑郁症状的抗抑郁药，n = 12个健康对照，在SD之前和之后没有情绪障碍史，以提供对SD抗抑郁作用的神经底物的机械洞察力。假设SD诱导的并发功能活动和与不同抑郁症状维度有关的多个脑网络的连通性变化，包括情绪调节，注意力，唤醒，自我指出和奖励处理将是SD的快速瞬时抗抑郁作用的基础。使用ABA设计，将在正常睡眠后的基线，总SD的一个晚上，使用实验室协议中的5天睡眠后的一晚恢复睡眠后，将在基线后在基线后在基线后在基线后获得多模式的脑成像（EEG）（EEG）（EEG）（EEG）和神经行为测试数据。具有抑郁症，神经影像学，睡眠和计时生物学专业知识的研究人员的跨学科团队将使用最先进的方法进行合作进行该项目。该项目的结果不仅将阐明SD快速抗抑郁作用的基础的神经元机制，而且还会产生基于大脑的生物标志物，以预测或监测对SD的个人反应以及药物和神经调节性干预措施的潜在新靶标。