Kunz D
Dept. of Psychiatry and Psychotherapy, Charité Campus Mitte - Universitätsmedizin.
Pharmacopsychiatry. 2004 Jul;37(4):139-46. doi: 10.1055/s-2004-827167.
Twenty years ago, chronobiology was a major topic in medical research, especially in psychiatry. Over time, however, clinicians lost interest in the subject because studies had failed to lead to any practical benefits for patient diagnosis or therapy. Today, the field of chronobiology appears to be on the verge of a renaissance. Over the past decade, our understanding of the basic mechanisms of the circadian timing system (CTS) has increased so rapidly that experts in the field sometimes speak of a "clockwork explosion." It has become apparent that, in order to treat circadian rhythm disturbances, new diagnostic tools are needed so that researchers and physicians can make reliable measurements of CTS functionality (e.g., phase position and circadian rhythm amplitude). Although clinicians do have a phase marker for the CTS at their disposal, there are still no reliable markers for CTS output strength as measured by rhythm amplitude. The amplitude is considered to be the most important factor in CTS output because it determines the degree of temporal organization in human and animal physiology. In this paper, we would like to suggest that circadian sleep propensity (CSP) - the endogenously generated 24-hour variation in the drive to wakefulness and sleep - is the product of all circadian rhythms, serving the human brain at night by assisting it in the production of good-quality sleep. If this is indeed the case, developing a CSP index (CSPI) for use in routine polysomnography would be of great value. In addition, we will review current data on melatonin and its relationship to sleep, basing our analysis on the assumption that melatonin is a circadian hormone and a drug with highly time-dependent effects. Because of this special mode of action, future melatonin studies should employ a special chronobiotic protocol that precludes the use of crossover designs and requires outcome measures different from those used in studies on classical hypnotics.
二十年前，时间生物学是医学研究尤其是精神病学中的一个主要课题。然而，随着时间的推移，临床医生对该课题失去了兴趣，因为研究未能为患者诊断或治疗带来任何实际益处。如今，时间生物学领域似乎正处于复兴的边缘。在过去十年中，我们对昼夜节律计时系统（CTS）基本机制的理解迅速增加，以至于该领域的专家有时会谈到“生物钟爆炸”。显而易见的是，为了治疗昼夜节律紊乱，需要新的诊断工具，以便研究人员和医生能够对CTS功能（如相位位置和昼夜节律幅度）进行可靠测量。尽管临床医生确实有一个CTS的相位标记可供使用，但对于通过节律幅度测量的CTS输出强度，仍然没有可靠的标记。幅度被认为是CTS输出中最重要的因素，因为它决定了人类和动物生理学中的时间组织程度。在本文中，我们想提出昼夜睡眠倾向（CSP）——内源性产生的24小时清醒和睡眠驱动力变化——是所有昼夜节律的产物，通过协助大脑产生高质量睡眠，在夜间为人类大脑服务。如果确实如此，开发一种用于常规多导睡眠图的CSP指数（CSPI）将具有很大价值。此外，我们将回顾关于褪黑素及其与睡眠关系的当前数据，我们的分析基于这样一个假设，即褪黑素是一种昼夜节律激素和一种具有高度时间依赖性效应的药物。由于这种特殊的作用方式，未来的褪黑素研究应该采用一种特殊的时间生物学方案，该方案排除交叉设计的使用，并要求采用与经典催眠药研究中使用的结果测量方法不同的方法。
