Circadian pathology in delayed sleep phase syndrome and non-24 hour sleep-wake syndrome Makoto UCHIYAMA 1 , Yuich KAMEI 2 , Kayo SHIBUI 2 , Keiko KIM 1 , Xin TAN 1 , Akiko OZAKI 1 , Hiroyuki SUZUKI 1 , Kenichi KURIYAMA 1 , Sayaka ARITAKE 1 , Hirokuni TAGAYA 1 , Tatsuro HAYAWA 1 1Department of Physiology, National Institute of Mental Health, National Center of Neurology and Psychiatry 2Department of Psychiatry, Kohnodai Hospital, National Center of Neurology and Psychiaty Keyword: 概日リズム , 睡眠・覚醒 , 生物時計 , メラトニン pp.806-816
Published Date 2001/10/10
DOI https://doi.org/10.11477/mf.1431901473
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 Recent studies in clinical chronobiology have revealed that a chronic sleep phase delay (delayed sleep phase syndrome (DSPS) ), or a chronic free-running sleep-wake rhythm (non-24 hour sleep-wake syndrome (non-24) ) was observed in sighted subjects living under a normal light-dark cycle. The intensity or timing of environmental light is suspected to play an etiologic role in sighted patients suffering from DSPS or non-24. Though these disorders have been studied for about 20 years, there have been few hypotheses on their pathophysiology. Here, we review articles on DSPS and non-24 with special reference to the phase relation between sleep and the circadian pacemaker, together with documentation of our recent study which focused on the syndromes.

 Our review of the recent literatures has revealed that an entraining mechanism of biological clock may be responsible for the clinical manifestation of DSPS and non 24, and that the assumed prolongation of tau (period) may be a main cause of these delayed syndromes. But, detailed pathophysiology or etiologic hypothesis has not been obtained except for Czeislers's deformed phase response curve theory on DSPS, in which less responsive advanced portion could explain the phase delay.

 We propose a new hypothesis on the pathophysiology of DSPS and non-24 based on our recent studies. The aim of this hypothesis is to answer the question why the patient's circadian pacemaker fails to properly reentrain to a 24-hour cycle after the phase delay of a sleep episode, but not the question why the patient's sleep begins to be phase-delayed or to be free-running, because the modern life in industrial countries is filled with opportunities to sleep phase delay. We carried out simultaneous measurement of continuous rectal temperature (BT) and wrist activity on patients with DSPS and non-24 to clarify this issue. We found that sleep length and the interval from the body temperature trough (BT trough) to sleep offset were significantly longer in both non-24 and DSPS patients than in the controls, and that the interval between sleep onset and the BT trough was significantly shorter in the non-24 patients than in the DSPS patients and the controls.

 We postulate these alterations in phase relation between sleep timing and core body temperature rhythm to be associated with phase changes of the circadian pacemaker via different illumination timings. The finding of a longer interval from BT trough to sleep-offset in non-24 and DSPS suggests that their inability to normally phase-advance their circadian rhythms may be a consequence of masking of the advance portion of their phase response curve by the last hours of their longer sleep episodes. The observation that the non-24 patients had a shorter interval between sleep onset and the BT trough than the DSPS patients and the controls indicates that the patient's phase-delay portion of the phase response curve to light might be inappropriately illuminated by light, leading to sleep-wake cycle that is longer than 24 hours. Moreover, we first found, by using a ultra-short sleep-wake schedule, that such alterations in phase angle between sleep timing and the circadian pacemaker in non-24 and DSPS may be caused by a poor compensatory function for sleep loss (a homeostatic regulation of sleep).

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