Circadian and Ultradian Cortisol Rhythms in Chronic Sleep Continuity Disturbance

慢性睡眠连续性障碍中的昼夜节律和超昼夜皮质醇节律

• 批准号: 10407957
• 负责人: Ivan Vargas
• 金额: $ 15.38万
• 依托单位: UNIVERSITY OF ARKANSAS AT FAYETTEVILLE
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-10-01 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10407957
• 关键词: Acute; Affect; Area; Area Under Curve; Arousal; Behavioral; Blood; Blood specimen; Chronic; Chronic Insomnia; Data; Development; Disease; Educational Activities; Educational workshop; Electroencephalography; Etiology; Exhibits; Fellowship; Fostering; Frequencies; Functional disorder; Health; Hour; Hydrocortisone; Impairment; Incidence; Individual; Knowledge; Laboratories; Link; Maintenance; Medical; Medicine; Mental Depression; Mentored Patient-Oriented Research Career Development Award; Mentors; Mentorship; Methodology; Neurobiology; Neuroendocrinology; Neurosecretory Systems; Outcome; Patients; Pattern; Periodicity; Persons; Phase; Physiologic pulse; Physiology; Plasma; Population; Prevalence; Production; Professional Ethics; Public Health; Publishing; Reading; Recording of previous events; Reporting; Research; Research Personnel; Research Training; Resources; Risk; Risk Factors; Sampling; Series; Severities; Sleep; Sleeplessness; Stress; Time; Training; Training Activity; United States; Wakefulness; Work; alternative treatment; base; career development; circadian; cost; data modeling; design; evidence base; experience; flexibility; hypothalamic-pituitary-adrenal axis; novel strategies; novel therapeutic intervention; patient oriented research; pedagogical content; screening; secondary analysis; skills; sleep onset; societal costs; symposium; symptomatology; treatment strategy

ABSTRACT Approximately 30-50% of the US population experiences acute sleep continuity disturbance (i.e., insomnia) per annum, and approximately 10% of the population report chronic levels of insomnia. Chronic insomnia (CI) is associated with significant daytime impairment and is a substantial risk factor for multiple psychiatric and medical disorders. Given CI's prevalence and consequences, it is essential to identify factors that perpetuate this disorder. One of the leading candidates for the neurobiological basis of CI is hypothalamic-pituitary-adrenal (HPA) axis dysregulation, specifically, alterations in cortisolinergic tone. Cortisol secretory patterns exhibit both a circadian and an ultradian rhythm. Ultradian pulses (i.e., every 60-120 minutes) are hypothesized to be involved in the maintenance of wakefulness during the day and may be related to the inhibition of wakefulness at night (i.e., the inhibition of pulses promotes the consolidation of sleep). While cortisol pulses naturally occur with transient awakenings, we hypothesize that these pulses can become a conditioned phenomenon in CI that predisposes the individual to awaken and/or experience prolonged nocturnal awakenings. Increased cortisol pulses during the day may also be expected because of the increased effort required to maintain wakefulness, and in turn, these increased pulses may further condition the aberrant occurrence of cortisol pulses at night. The scientific aims are (1) to evaluate whether subjects with CI, as compared to good sleepers, exhibit greater ultradian cortisol pulsatility during the day and/or at night, and (2) to quantify the association between ultradian cortisol secretion and metrics related to spontaneous awakenings from sleep (i.e., timing, frequency, duration, and EEG spectral profile of the awakenings). The proposed study will be conducted as a between-subjects design, examining 20 individuals with CI and 20 good sleepers during two consecutive nights in the laboratory (Night 1 is a screening night). While in the lab, blood will be sampled every 10 minutes for 24 hours and sleep will be polysomographically recorded. A refined delineation of both the circadian and ultradian aspects of cortisol secretion may allow for a better understanding of the etiology of chronic insomnia, the efficacy of established treatments, and potentially the development of new therapeutic approaches. The training plan includes educational activities that encompass three broad topic areas: (1) general skills (i.e., professional, ethics, and research training activities), (2) principles and practice and methodology issues related to neuroendocrinology, and (3) principles and practice and methodology issues related to behavioral sleep medicine and sleep medicine. The training plan builds upon the applicant's background in depression-related sleep research and stress physiology and provides the necessary training in neuroendocrinology, behavioral sleep medicine, and sleep medicine to further explore and document any association of HPA-axis abnormalities with persistent wakefulness at night. The pedagogic approach includes routine one-on-one mentorship, directed readings, course work, mini-fellowships, lab-based trainings, and conferences/workshops.

抽象的 大约 30-50% 的美国人每人经历急性睡眠连续性障碍（即失眠） 每年，大约 10% 的人口患有慢性失眠症。慢性失眠（CI）是 与显着的日间损害有关，是多种精神和疾病的重要危险因素 医疗疾病。鉴于 CI 的普遍性和后果，有必要确定导致 CI​​ 持续存在的因素 这种紊乱。 CI 神经生物学基础的主要候选者之一是下丘脑-垂体-肾上腺 （HPA）轴失调，特别是皮质醇能张力的改变。皮质醇分泌模式同时表现出 昼夜节律和亚昼夜节律。超电脉冲（即每 60-120 分钟一次）被假设为 参与白天清醒的维持，可能与抑制清醒有关 晚上（即抑制脉搏促进睡眠的巩固）。虽然皮质醇脉冲自然发生 对于短暂的觉醒，我们假设这些脉冲可以成为 CI 中的条件现象， 使个体容易醒来和/或经历长时间的夜间觉醒。皮质醇增加 由于保持清醒所需的努力增加，白天的脉搏也可能是预期的， 反过来，这些增加的脉冲可能进一步调节夜间皮质醇脉冲的异常发生。 科学目标是 (1) 评估患有 CI 的受试者与睡眠良好的受试者相比是否表现出更大的 白天和/或夜间的超电皮质醇脉动，以及（2）量化超电之间的关联 皮质醇分泌和与睡眠自发觉醒相关的指标（即时间、频率、持续时间、 和觉醒的脑电图频谱轮廓）。拟议的研究将作为受试者之间的研究进行 设计，在实验室连续两个晚上检查 20 名 CI 患者和 20 名睡眠良好的人 （第一晚是放映之夜）。在实验室期间，24 小时内每 10 分钟采集一次血液样本并睡觉 将进行多导睡眠监测记录。昼夜节律和超昼夜节律方面的精确描述 皮质醇的分泌可能有助于更好地了解慢性失眠的病因、 已建立的治疗方法，并可能开发新的治疗方法。培训计划 包括涵盖三个广泛主题领域的教育活动：(1) 一般技能（即专业、 道德和研究培训活动），(2) 相关原则、实践和方法论问题 神经内分泌学，以及（3）与行为睡眠相关的原理、实践和方法论问题 药和睡眠药。培训计划以申请人的抑郁症相关背景为基础 睡眠研究和压力生理学，并提供神经内分泌学、行为学方面的必要培训 睡眠医学和睡眠医学进一步探索和记录 HPA 轴的任何关联 夜间持续清醒的异常。教学方法包括常规的一对一 指导、定向阅读、课程作业、小型奖学金、实验室培训和会议/研讨会。