After-Effects of Entrainment on Human Circadian Period

直到最近，人们还普遍认为人类昼夜节律起搏器的内在周期是25h。然而，使用基于实验室的强制去同步法，我们发现昼夜节律系统的内在周期接近24h(平均24.18h)。同样，我们发现生活在社会中的无光感盲人有褪黑激素的昼夜节律，这种昼夜节律自由运行，平均周期约为24.5h。虽然这些数据也表明内在的昼夜节律周期比以前认为的更接近24h，但盲人和有视力的受试者之间的差异表明，昼夜节律起搏器可能受到不明因素的影响。一个可能的因素是，在非夹带盲人中，没有夹带对24小时明暗周期的后遗症，因此他们的昼夜节律周期可能比从夹带中观察到的有视力的受试者更长。类似地，由于光同步器和非光同步器的后效不同，在社会中被非光时间线索缠绕的盲人受试者在从缠绕中释放时可能不同于有视力和非被缠绕的盲人受试者。我们建议通过评估盲人个体在野外和强迫去同步化条件下的昼夜节律周期，并将他们与已经和将被研究的健康视力受试者进行比较，来研究夹带的后遗症的作用。具体地说，我们将检验假设：1)NPL受试者的褪黑素和温度节律的内源性昼夜节律周期显著长于有视力的受试者；2)在非光时间线索非均匀分布的野外条件下观察到的NPL受试者的昼夜节律周期显著长于在受控强迫去同步条件下评估的被试；3)那些被困在社会中但对光不敏感的NPL受试者的昼夜节律周期平均将显著短于那些没有被困在社会中的NPL受试者。这项工作对于理解内在周期与先前夹带的关系以及夹带的后效的作用具有重要的意义。它将有助于确定非光学同步器的携带限度，并将评估这种时间线索在盲人和视力正常人群中治疗昼夜节律睡眠-觉醒障碍的效果。

Until recently, it was widely believed that the intrinsic period of the human circadian pacemaker was 25 h. However, using a 'forced desynchrony' laboratory-based protocol in which the confounding effects of light and activity on circadian period assessment are controlled, we have found that the intrinsic period of the circadian system is close to 24 h (average 24.18 h). Similarly, we have found that blind individuals without light perception (NPL) living in society have circadian rhythms of melatonin which free-run with a period averaging approximately 24.5 h. While these data also suggest that the intrinsic circadian period is closer to 24 h than previously thought, the discrepancy between blind and sighted subjects suggests that the circadian pacemaker may be affected by unidentified factors. One likely factor is the absence of after- effects of entrainment to the 24 h light-dark cycle in non- entrained blind individuals, who may thus have a longer circadian period than sighted subjects observed upon release from entrainment. Similarly, blind subjects entrained by non-photic time cues in society may differ from sighted and non-entrained blind subjects upon release from entrainment due to differences in after-effects of photic- and non-photic synchronizers. We propose to investigate the role of after-effects of entrainment by assessing the circadian period of blind individuals under field and forced desynchrony conditions and comparing them to healthy sighted subjects who have been and will be studied. Specifically we will test the hypotheses that: 1) the endogenous circadian period of the melatonin and temperature rhythms is significantly longer in NPL subjects than sighted subjects; 2) the circadian period of NPL subjects observed in field conditions in which non-photic time cues are non-uniformly distributed is significantly longer than when assessed under controlled forced desynchrony conditions; 3) those NPL subjects who are entrained in society but who are insensitive to light will have, on average, a significantly shorter circadian period than those NPL subjects who are not entrained in society. This work has significant implications for understanding how intrinsic period relates to prior entrainment and the role of after-effects of entrainment. It will help define the limits of entrainment for non-photic synchronizers and will evaluate the efficacy of such time cues to treat circadian rhythm sleep-wake disorders in both the blind and sighted populations.