Sleep, Aging and Circadian Rhythm Disorders

描述（申请人提供）：睡眠不足是美国人的一个主要健康和安全问题。全国民意调查显示，超过四分之一的18-84岁的成年人每晚睡眠时间少于7小时，15%的人每晚睡眠时间少于6小时。与睡眠不足相关的警觉性和表现能力的缺陷可能会导致更大的汽车事故，家庭和工作场所事故的风险，以及困倦者的工作失误。睡眠不足也会对生活质量产生负面影响，影响易怒，情绪和动力。尽管认识到的峰值性能的时间和在急性睡眠剥夺的反应个体间的差异，很少有人知道关于慢性和急性睡眠剥夺的反应个体间的差异。最近的一系列研究结果表明，基因多态性在对急性睡眠丧失/昼夜节律失调的反应以及对最常用的促醒治疗剂咖啡因的敏感性方面具有相当大的个体间差异。然而，这些研究并没有研究个体间对慢性睡眠限制的反应差异，也没有研究昼夜节律和自我平衡对警觉性和认知能力的贡献的个体间差异。客观表现、主观警觉性和睡眠的两个主要决定因素是昼夜节律和睡眠-觉醒稳态。最近，生物钟基因PER 3的遗传多态性与睡眠、觉醒时间表现和对睡眠剥夺的反应的个体间差异有关，PER 3 *1* 个体在长时间觉醒期间睡眠和表现更好，而PER 3515个体在昼夜节律相位提前后睡眠和表现更好。因此，拟议工作的目标是评估PER 3基因多态性个体的表型，这些多态性已知会影响睡眠稳态和昼夜节律。我们建议研究6个健康人与PEF？3例为M基因型，6例为PER 3515基因型。该方案将包括23天的住院治疗和2周的强迫睡眠程序中的慢性睡眠限制，这将使我们能够调查昼夜节律和觉醒依赖性对警觉性和表现的贡献，随后是一次40小时的睡眠剥夺，这将使我们能够调查对慢性睡眠限制后急性睡眠剥夺发作的反应。我们将记录睡眠和清醒时的EEC，并测试认知功能，警觉性和情绪的多个方面。公众相关性：这项研究的结果对于理解慢性和急性睡眠不足的后果具有重要意义。大多数成年人经常无法获得充足的睡眠，但很少有研究试图量化这种不利情况下的个体差异。了解PER 3414和PER 3515个体的警觉性和表现如何对睡眠不足做出反应，将提供关于睡眠、昼夜节律生物学、神经行为表现和遗传学相互作用的所需信息。

DESCRIPTION (provided by applicant): Insufficient sleep is a major health and safety problem for Americans. National polls indicate that more than a quarter of adults 18-84 years of age regularly sleep less than 7 h per night, with 15% reporting sleeping less than 6 h per night. The deficits in alertness and performance ability associated with insufficient sleep can lead to greater risk for automobile accidents, home and workplace accidents, and on-the-job errors in sleepy individuals. Insufficient sleep can also have a negative effect on the quality of life, with impacts on irritability, mood, and motivation. Despite recognition of inter-individual differences in the timing of peak performance and in the response to acute sleep deprivation, very little is known regarding inter-individual differences in response to both chronic and acute sleep deprivation. A series of recent findings have revealed that genetic polymorphisms account for considerable inter-individual variations in the response to acute sleep loss/circadian misalignment and in sensitivity to the most commonly used wake-promoting therapeutic, caffeine. These studies, however, have not examined the inter-individual differences in response to chronic sleep restriction, nor have they examined the inter-individual differences in circadian and homeostatic contributions to alertness and cognitive performance. Two major determinants of objective performance, subjective alertness and sleep are circadian phase and sleep-wake homeostasis. Recently, a genetic polymorphism in the circadian clock gene PER3 has been linked to inter-individual differences in sleep, wake-time performance and response to sleep deprivation, with PER3*1* individuals sleeping and performing better during prolonged wake episodes while PER3515 individuals sleep and perform better after circadian phase advances. Therefore, the goal of the proposed work is to evaluate the phenotype of individuals with polymorphisms in the PER3 gene that are known to affect sleep homeostasis and circadian rhythms in performance. We propose to study 6 healthy individuals with the PEf?3"M genotype and 6 with the PER3515 genotype. The protocol will include a 23-day inpatient stay with 2 weeks of chronic sleep restriction in a forced desynchrony procedure, which will enable us to investigate both the circadian and wake-dependent contributions to alertness and performance, followed by one 40-hr sleep deprivation, which will enable us to investigate the response to an episode of acute sleep deprivation following chronic sleep restriction. We will record sleep and waking EEC, and test for multiple aspects of cognitive functioning, alertness and mood. PUBLIC RELEVANCE: Results from this study have important implications for understanding the consequences of chronic and acute insufficient sleep. Most adults regularly fail to get sufficient sleep, but few studies have attempted to quantify the inter-individual differences in response to this adverse situation. Knowledge of how the alertness and performance of PER34'4 and PER3515 individuals respond to insufficient sleep will provide needed information about the interaction of sleep, circadian biology, neurobehavioral performance and genetics.