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％的美国人口经历急性睡眠连续性障碍（即失眠） 一年，大约10％的人口报告了慢性失眠水平。慢性失眠（CI）是 与白天的重大损害相关，是多种精神科和 医疗疾病。鉴于CI的流行和后果，必须确定因素永久的因素 这个疾病。 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）轴功能障碍，特别是皮质素能张力的改变。皮质醇分泌模式都表现出 昼夜节律。假设超级脉冲（即每60-120分钟）为 白天涉及维护清醒，可能与抑制清醒有关 晚上（即抑制脉冲会促进睡眠的巩固）。皮质醇脉冲自然发生 通过短暂的觉醒，我们假设这些脉冲可以成为CI中的条件现象 容易使人觉醒和/或经历长时间的夜间觉醒。皮质醇增加 由于维持清醒所需的努力，可能还可以预期白天的脉冲 反过来，这些增加的脉冲可能会进一步调节夜间皮质醇脉冲的异常。 科学目的是（1）评估CI的受试者与良好的卧铺相比是否表现出更大的 在白天和/或晚上和/或晚上和/或（2）量化超质量之间的关联 皮质醇分泌和指标与睡眠的自发觉醒有关（即时机，频率，持续时间， 和觉醒的脑电图谱）。拟议的研究将作为受试者间进行 设计，在实验室连续两个晚上检查20名CI和20个好卧铺的人 （晚上1是放映之夜）。在实验室中，血液每10分钟进行一次抽样24小时并入睡 将记录在多个学上。昼夜节律的精致描绘 皮质醇分泌可以更好地理解慢性失眠的病因，即 建立的治疗方法，并有可能发展新的治疗方法。培训计划 包括包括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）与 神经内分泌学，以及（3）与行为睡眠有关的原理，实践和方法论问题 医学和睡眠医学。培训计划以抑郁相关的申请人背景为基础 睡眠研究和压力生理学，并提供神经内分泌学，行为的必要培训 睡眠药物和睡眠医学，以进一步探索和记录任何HPA轴关联 晚上持续的清醒异常。教学方法包括例行一对一 指导，定向阅读，课程工作，迷你货币，基于实验室的培训和会议/研讨会。