Division of Sleep and Circadian Disorders, Departments of Medicine and Neurology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Division of Sleep Medicine, Harvard Medical School, Boston, Massachusetts, USA.
JCI Insight. 2017 Apr 6;2(7):e89494. doi: 10.1172/jci.insight.89494.
In humans, a single light exposure of 12 minutes and multiple-millisecond light exposures can shift the phase of the circadian pacemaker. We investigated the response of the human circadian pacemaker to a single 15-second or 2-minute light pulse administered during the biological night. Twenty-six healthy individuals participated in a 9-day inpatient protocol that included assessment of dim light melatonin onset time (DLMO time) before and after exposure to a single 15-second ( = 8) or 2-minute ( = 12) pulse of bright light (9,500 lux; 4,100 K fluorescent) or control background dim light (<3 lux; = 6). Phase shifts were calculated as the difference in clock time between the two phase estimates. Both 15-second and 2-minute exposures induced phase delay shifts [median (± SD)] of -34.8 ± 47.2 minutes and -45.4 ± 28.4 minutes, respectively, that were significantly ( = 0.04) greater than the control condition (advance shift: +22.3 ± 51.3 minutes) but were not significantly different from each other. Comparisons with historic data collected under the same conditions confirmed a nonlinear relationship between exposure duration and the magnitude of phase shift. Our results underscore the exquisite sensitivity of the human pacemaker to even short-duration single exposures to light. These findings may have real-world implications for circadian disruption induced by exposure to brief light stimuli at night. The study was registered as a clinical trial on www.clinicaltrials.org, NCT #01330992. Funding for this study was provided by NSBRI HFP02802 and NIH P01-AG09975, R01-HL114088 (EBK), RC2-HL101340-0 (EBK, SWL, SAR, REK), K02-HD045459 (EBK), K24-HL105664 (EBK), T32-HL07901 (MSH, SAR), HL094654 (CAC), and AG044416 (JFD). The project described was supported by NIH grant 1UL1 TR001102-01, 8UL1TR000170-05, UL1 RR 025758, Harvard Clinical and Translational Science Center, from the National Center for Advancing Translational Science.
在人类中,单次 12 分钟的光照和多次毫秒级的光照都可以改变生物钟的相位。我们研究了人类生物钟对单次 15 秒或 2 分钟光脉冲的反应,这些光脉冲是在生物夜间进行的。26 名健康个体参加了一项为期 9 天的住院协议,该协议包括在接受单次 15 秒(= 8)或 2 分钟(= 12)的强光脉冲(9500 勒克斯;4100 K 荧光)或对照背景弱光(<3 勒克斯;= 6)照射前后测量褪黑素开始时间(DLMO 时间)。相位移是通过两个相位估计之间的时钟时间差计算得出的。15 秒和 2 分钟的暴露都分别导致 -34.8±47.2 分钟和-45.4±28.4 分钟的相位延迟(= 0.04),明显大于对照组(提前移相:+22.3±51.3 分钟),但彼此之间没有显著差异。与在相同条件下收集的历史数据进行比较,证实了暴露持续时间与相移幅度之间存在非线性关系。我们的研究结果强调了人类起搏器对即使是短时间的单次光暴露也具有极高的敏感性。这些发现可能对夜间短暂光刺激引起的生物钟紊乱产生实际影响。该研究在 www.clinicaltrials.org 上作为临床试验进行注册,NCT #01330992。本研究由 NSBRI HFP02802 和 NIH P01-AG09975、R01-HL114088(EBK)、RC2-HL101340-0(EBK、SWL、SAR、REK)、K02-HD045459(EBK)、K24-HL105664(EBK)、T32-HL07901(MSH、SAR)、HL094654(CAC)和 AG044416(JFD)资助。该项目由 NIH 拨款 1UL1 TR001102-01、8UL1TR000170-05、UL1 RR 025758、哈佛临床与转化科学中心、国家转化科学推进中心资助。