Yale Child Health Research Center, Yale University, New Haven, Connecticut 06520
Address all correspondence and requests for reprints to: Scott A. Rivkees, M.D., Yale Child Health Research Center, Yale University, New Haven, Connecticut 06520.
In a novel and important set of clinical studies reported in this issue of JCEM, Aeschbach et al. (1) examined long- and short-sleepers, who sleep greater than 9 h or less than 6 h per night, respectively. Assessing melatonin and cortisol levels and monitoring body temperature, they found a longer "biological night" in long-sleepers than in short-sleepers, which is characterized by a greater duration of nocturnal melatonin secretion and later early morning temperature nadirs and cortisol peaks (1). Thus, physiological processes that mark the output of the circadian timing system parallel sleep duration.
The findings of Aeschbach et al. (1) give credence to everyday observations that sleep needs vary individually and suggest that the amount of sleep we need reflects intrinsic factors. These observations also underlie why it is difficult to change sleep patterns, if we are fighting inherent physiology.
The notion that ones sleep duration is intrinsically determined has widespread implications in many disciplines, including industry, healthcare, and education. "Sleep debt" caused by sleep deprivation is a recognized cause of industrial accidents and impaired worker productivity (2). For example, roadway accidents are more common in sleep-deprived truck drivers (3). The productivity of air traffic controllers is adversely affected by shift work, as well (4).
The excessive work hours of medical house officers, who work through the night when "on-call," has raised concern about patient safety. Understandably, this issue has caught the scrutiny of legislators and regulatory agencies (5). These efforts have resulted in new policies that limit work hours by medical staff.
Not only are we curtailing the sleep of adults in the name of productivity, the educational system is cutting into the sleep of children and adolescents. In many educational districts, the school day begins in early morning hours (6). It is not uncommon to see children standing on street corners awaiting the school buses in early morning darkness. Reflecting the fact that it is difficult to advance the hands on ones biological clock irrespective of age, adverse effects from reduced sleep and early morning awakening on academic performance are being increasingly recognized in children and adolescents (6).
We live in a society in which we can control our photic environment through the simple flip of a switch or the more convenient clap of the hands. Using alarm clocks and planned schedules, we believe that we can override our natural sleep needs. We believe that we can comfortably live our lives out of synchrony with the 24-h light-dark cycle, and reverse our days and nights without penalty. However, as reflected by the ever-increasing number of businesses devoted to optimizing schedules of shift workers, it is difficult to willfully change sleep habits and the hands of the circadian clock.
It was thought that by exposing shift workers to bright light at night, the circadian clock could be reset. Yet, unless stringent efforts are made to limit daytime lighting exposure, resetting of the biological clock will not occur, and melatonin and cortisol rhythms may remain out of phase with periods of sleep and wakefulness (7). Individuals working at night may, thus, be out of phase with their optimal periods of alertness and task performance. Efforts to develop agents to reset the circadian clock (i.e. "jet lag drugs") have also been largely unrealized (8). Despite the popular hype that melatonin can conveniently shift circadian phase, data to support this notion are not striking and show modest effects at best (9, 10).
Just as it is difficult to change ones circadian phase, the observations of Aeschbach et al. (1) provide a basis for why it is difficult to change sleep habits. Because the duration of the biological night varies individually, it may be more difficult for some individuals to adapt to condensed sleep schedules than others. Strategies and guidelines aimed at improving health and productivity of shift workers may, therefore, be effective for some individuals, but ineffective for others.
The biological basis of variability in sleep duration is unknown at present and remains an intriguing issue. An evolving body of evidence suggests that the sleep cycle and circadian rhythmicity are integrally related, with the circadian system influencing both the timing and duration of sleep. Expressed circadian rhythms, like the sleep-wake cycle and rhythms in hormone production, are generated and regulated by a biological clock located in the suprachiasmatic nuclei (SCN) in the anterior hypothalamus (11). Damage to these nuclei results in episodes of sleep and wakefulness occurring throughout the 24-h day, rather than being consolidated at night. SCN damage also results in an increase in the total duration of sleep in primates (12).
Over the past decade, the dissection of the molecular hands of the circadian clock has lead to fascinating new insights. The generation of circadian rhythms seems to be related to the complex interaction of a handful of transcriptional regulators and kinases, resulting in 24-h cycles of protein expression and action in the SCN (11). In mammals these factors include the proteins PERIOD, CLOCK, CRY, BMAL, and casein kinase 1 (11). Mutations in some of these factors have been discovered recently.
In humans, mutations in PERIOD-2 are associated with the advanced circadian phase syndrome (13). Individuals with this condition wake very early in the morning and retire to bed at early evening hours. In animals, mutations in CLOCK result in abnormal, disorganized sleep problems (14). Mutations in casein kinase 1 result in a short circadian day (period) (15).
Whereas it is possible to localize the circadian clock in mammals to a discrete region in the brain, the brain regions involved in sleep organization are far more diffuse, involving complex subcortical networks (16). Similar to how clock-gene mutations are providing insights into the biological basis of circadian rhythmicity, the discovery of novel proteins has also provided insights in the pathogenesis of sleep disorders (17, 18, 19). The inability to produce or respond to orexin/hypocretin has been found to be a cause of narcolepsy (17), and it is likely that this seminal discovery will lead to new diagnostic tests and treatment for this disorder (17).
By coupling our knowledge of basic clock and sleep mechanisms with powerful genetic approaches that permit the identification of specific genes in small cohorts, it is likely that there will be further identification and elucidation of factors that regulate the duration and timing of sleep (18). The continued characterization of individual variation in sleep and the identification of families and cohorts with unusual sleep and circadian properties will also greatly enhance genetic approaches in this regard. Thus, we may someday learn why some individuals have the ability to stay up and watch David Letterman after the 11 oclock news, whereas others retire before the news at 10 oclock.
Society, industry, and medicine are becoming increasingly aware of the importance of sleep and the proper timing of sleep cycles, as reflected by sleep- and work-hour-related laws. However, compared with the advances in our understanding of basic sleep and circadian physiology and molecular biology, public attention in this arena has lagged considerably. We can readily manipulate our photic environment, yet we stubbornly recognize how difficult it is to overcome "mother nature" and change the timing of and the amount of sleep we need. Increasingly, we seem to value our alarm clocks more than our internal clocks. Thus, an important challenge of our modern and fluid society is to be able to accommodate our normal circadian cycle and our individual sleep requirements in the name of progress and productivity.
Acknowledgments
Footnotes
Abbreviation: SCN, Suprachiasmatic nuclei.
Received November 8, 2002.
Accepted November 10, 2002.
References
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