Turner Institute for Brain and Mental Health, School of Psychological Sciences, Faculty of Medicine, Nursing and Health Sciences, Monash University, Australia.
J Biol Rhythms. 2020 Dec;35(6):628-640. doi: 10.1177/0748730420962598. Epub 2020 Oct 16.
There is large interindividual variability in circadian timing, which is underestimated by mathematical models of the circadian clock. Interindividual differences in timing have traditionally been modeled by changing the intrinsic circadian period, but recent findings reveal an additional potential source of variability: large interindividual differences in light sensitivity. Using an established model of the human circadian clock with real-world light recordings, we investigated whether changes in light sensitivity parameters or intrinsic circadian period could capture variability in circadian timing between and within individuals. Healthy participants ( = 12, aged 18-26 years) underwent continuous light monitoring for 3 weeks (Actiwatch Spectrum). Salivary dim-light melatonin onset (DLMO) was measured each week. Using the recorded light patterns, a sensitivity analysis for predicted DLMO times was performed, varying 3 model parameters within physiological ranges: (1) a parameter determining the steepness of the dose-response curve to light (), (2) a parameter determining the shape of the phase-response curve to light (), and (3) the intrinsic circadian period (). These parameters were then fitted to obtain optimal predictions of the three DLMO times for each individual. The sensitivity analysis showed that the range of variation in the average predicted DLMO times across participants was 0.65 h for , 4.28 h for , and 3.26 h for . The default model predicted the DLMO times with a mean absolute error of 1.02 h, whereas fitting all 3 parameters reduced the mean absolute error to 0.28 h. Fitting the parameters independently, we found mean absolute errors of 0.83 h for , 0.53 h for , and 0.42 h for . Fitting and together reduced the mean absolute error to 0.44 h. Light sensitivity parameters captured similar variability in phase compared with intrinsic circadian period, indicating they are viable targets for individualizing circadian phase predictions. Future prospective work is needed that uses measures of light sensitivity to validate this approach.
个体间的生物钟计时存在较大的变异性，而这种变异性在生物钟的数学模型中被低估了。传统上，通过改变内在的生物钟周期来对计时的个体差异进行建模，但最近的发现揭示了另一个潜在的可变性来源：个体间对光敏感度的巨大差异。我们使用具有真实世界光照记录的成熟的人体生物钟模型，研究了改变光敏感度参数或内在生物钟周期是否可以捕捉个体间和个体内的生物钟计时变异性。健康参与者（= 12 人，年龄 18-26 岁）接受了 3 周的连续光照监测（Actiwatch Spectrum）。每周测量唾液暗微光褪黑素起始时间（DLMO）。使用记录的光照模式，对预测的 DLMO 时间进行了敏感性分析，在生理范围内改变了 3 个模型参数：（1）决定光照剂量-反应曲线陡度的参数（），（2）决定光照相位反应曲线形状的参数（），以及（3）内在生物钟周期（）。然后拟合这些参数，以获得每个个体的三个 DLMO 时间的最佳预测值。敏感性分析表明，参与者之间平均预测 DLMO 时间的变化范围为 0.65 小时， 为 4.28 小时， 为 3.26 小时。默认模型预测 DLMO 时间的平均绝对误差为 1.02 小时，而拟合所有 3 个参数将平均绝对误差降低至 0.28 小时。独立拟合参数时，我们发现 、 、 的平均绝对误差分别为 0.83 小时、0.53 小时和 0.42 小时。拟合 和 可将平均绝对误差降低至 0.44 小时。与内在生物钟周期相比，光敏感度参数可捕捉到相似的相位变异性，这表明它们是实现个体生物钟相位预测个性化的可行目标。需要进行未来的前瞻性研究，使用光敏感度测量来验证这种方法。
