Chronobiotic protocol and circadian sleep propensity index: New tools for clinical routine and research on melatonin and sleep

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.\