PMC4770037_01
Actigraphy recording over 5 months (August-December 2012). Note the free-running rhythm of activity (black bars) and sleep-periods (lighter areas) with a calculated intrinsic period of tau = 25.27 h and a mean phase angle of 3.38 +- 2.27 h between dim light melatonin onset (DLMO) and sleep onset. Red spots: DLMO = 3 pg. The patient received 30 min BLT in the morning between October 21, 2012 and December 7, 2012 and oral melatonin in the evening from October 21, 2012 to October 24, 2012 (discontinued due to side effects). During the first days of treatment, sleep onset continued to free-run, while sleep offset remained relatively stable (for ~10 days).
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F1
While the results from the PSG were within the normal range (five NREM-REM cycles with slightly increased fragmentation due to short wake periods, sleep efficiency = 82% at 9 h time in bed, and normal proportions of sleep stages), the actigraphy recording showed a free-running sleep-wake rhythm with a phase length (tau) of 25.27 h (Figure 1). However, sleep onset still followed the original free-running rhythm with consecutive delays every day (Figure 1).
In-lab melatonin suppression test with bright light (BL: 10'000 lux). Schedule: the patient rose at 2:45 a.m. (according to his free-running rhythm), came to our lab at 10 a.m. and was kept under dim light conditions (<8 lux). Saliva samples for melatonin measurement were collected hourly from 11:00 a.m. on. DLMO (3 pg threshold, red dashed line) occurred at 2:16 p.m. The melatonin suppression test was scheduled from 4:30 p.m. to 5:39 p.m. with saliva samples in 15 min intervals. BL (yellow rectangle) caused a significant reduction of melatonin secretion, indicating a normal physiological response via an intact retina-RHT-pineal axis. The patient spent the following night in the lab for PSG recording with sleep onset at 6:40 p.m. and sleep offset at 3:45 a.m.
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F2
The melatonin suppression test by bright light (10,000 lux, see Figure 2) showed a normal response of the physiological LD-mediated melatonin release from the pineal gland.
Range of the intrinsic period length (based on data presented in Ref.; n = 157 healthy individuals). The length of the circadian period shows a rather large interindividual variability mimicking a bell distribution centered around 24.15 h (+-0.2 h) with extreme taus predisposing to the development of certain circadian rhythm disorders. However, the range of normal entrainment, as well as pathological alignment, seems to show rather large overlaps in the length of tau, indicating the influence of other factors in the determination of chronotypes and the development of circadian rhythm sleep disorders, respectively.
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F3
The internal period length (tau - tau) of individuals with normal sleep is in average slightly longer than the environmental LD cycle (about 24.15 +- 0.2 h, see Figure 3) with a shorter average tau in women (24.09 +- 0.2 h) than in men (24.19 +- 0.2 h).