Stability of melatonin and temperature as circadian phase markers and their relation to sleep times in humans
Stability of melatonin and temperature as circadian phase markers and their relation to sleep times in humans
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DOI：
10.1177/0748730404273983
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发表时间：
2005-04-01
影响因子：
3.5
通讯作者：
Zee, PC
中科院分区：
文献类型：
--
作者：
Benloucif, S;Guico, MJ;Zee, PC
核心体温和褪黑素的昼夜节律通常被用作昼夜节律钟的阶段标记。当在恒定的常规条件下测量时，褪黑素是一个更稳定的昼夜节律阶段标记。然而，对这些相标记物在较少控制条件下的可变性知之甚少。此外，对首选的分析方法几乎没有共识。本研究的目的是评估在自然环境中有规律睡眠时间表的受试者中计算褪黑激素和体温阶段的各种方法。研究人员分析了42名健康年轻受试者的基线数据，这些受试者至少接受了两次研究。每次住院间隔至少3周。受试者被要求保持有规律的睡眠时间表，入院前一周通过睡眠记录和活动记录仪监测。受试者在受控条件下度过一个习惯化之夜，然后收集基线温度和褪黑激素测量值。通过9种不同的方法评估褪黑激素节律的阶段。温度最低点（Tmin）估计使用克利夫兰和余弦曲线拟合程序，有和没有遮蔽。通过相关分析和阶段估计时间的平均绝对差来评估录取之间的可变性。通过睡眠开始或睡眠偏移与不同阶段标记的相关性来评估与睡眠时间的关系。褪黑素阶段标记物比Tmin的估计值更稳定，与睡眠时间的相关性更高。在估计Tmin的方法中，简单余弦分析是变量最小的。此外，与睡眠开始相比，睡眠偏移与各种阶段标记的相关性更强。褪黑激素抵消的相对测量值具有最高的相关系数，最低的研究间变异性，并且与睡眠时间的相关性比褪黑激素发作的相关性更强。分析方法的一致性表明，褪黑素谱下降阶段的趋势比褪黑素开始的标记物或褪黑素合成终止的措施更稳定和可靠。
Circadian rhythms of core body temperature and melatonin are commonly used as phase markers of the circadian clock. Melatonin is a more stable marker of circadian phase when measured under constant routine conditions. However, little is known about the variability of these phase markers under less controlled conditions. Moreover, there is little consensus about the preferred method of analysis. The objective of this study was to assess various methods of calculating melatonin and temperature phase in subjects with regular sleep schedules living in their natural environment. Baseline data were analyzed from 42 healthy young subjects who were studied on at least two occasions. Each hospital admission was separated by at least 3 weeks. Subjects were instructed to maintain a regular sleep schedule, which was monitored for 1 week before admission by sleep logs and actigraphy. Subjects spent one habituation night under controlled conditions prior to collecting baseline temperature and melatonin measurements. The phase of the melatonin rhythm was assessed by 9 different methods. The temperature nadir (Tmin) was estimated using both Cleveland and Cosine curve fitting procedures, with and without demasking. Variability between admissions was assessed by correlation analysis and by the mean absolute difference in timing of the phase estimates. The relationship to sleep times was assessed by correlation of sleep onset or sleep offset with the various phase markers. Melatonin phase markers were more stable and more highly correlated with the timing of sleep than estimates of Tmin. Of the methods for estimating Tmin, simple cosine analysis was the least variable. In addition, sleep offset was more strongly correlated with the various phase markers than sleep onset. The relative measures of melatonin offset had the highest correlation coefficients, the lowest study-to-study variability, and were more strongly associated with sleep timing than melatonin onsets. Concordance of the methods of analysis suggests a tendency for the declining phase of the melatonin profile to be more stable and reliable than either markers of melatonin onset or measures of the termination of melatonin synthesis.