Behaviorally and environmentally induced non-24-hour sleep-wake rhythm disorder in sighted patients

Abstract

Study objectives: To determine whether there was evidence of circadian or sleep-regulatory dysfunction in sighted individuals with non-24-hour sleep-wake rhythm disorder.

Methods: Three sighted individuals with signs and/or symptoms of non-24-hour sleep-wake rhythm disorder were studied. Thirty-five- to 332-day laboratory and home-based assessments of sleep-wake and circadian timing, endogenous circadian period, photic input to the circadian pacemaker, and/or circadian and sleep-wake-dependent regulation of sleep were conducted.

Results: No evidence of circadian dysfunction was found in these individuals. Instead, sleep-wake timing appeared to dissociate from the circadian timing system, and/or self-selected sleep-wake and associated light/dark timing shifted the circadian pacemaker later, rather than the circadian pacemaker determining sleep-wake timing.

Conclusions: These findings suggest that the etiology of this disorder may be light- and/or behaviorally induced in some sighted people, which has implications for the successful treatment of this disorder.

Citation: Emens JS, St Hilaire MA, Klerman EB, et al. Behaviorally and environmentally induced non-24-hour sleep-wake rhythm disorder in sighted patients. J Clin Sleep Med. 2022;18(2):453-459.

Keywords: circadian rhythm; circadian rhythm sleep disorders; light; melatonin; non–24-hour sleep-wake rhythm disorder.

Figure 1. Participant 1.

(A) Double-raster plot of the experimental protocol. Hours are along the horizontal axis and days down the vertical axis; 2 days are plotted across each horizontal line. Sleep timing is represented by the black (self-selected) and gray (scheduled) bars. Hatched bars show the constant routines and yellow bar the timing of the bright light for the melatonin suppression test. Red circles indicate the timing of the dim light melatonin onsets and the green circles are the model simulated time of the onset of melatonin synthesis. The calculated period (denoted by the Greek letter τ) for each segment using different metrics is shown to the right using the same color as in the raster plot (sw: sleep-wake; s: simulation; m: melatonin; t: temperature). Note instances (eg, day 76, orange arrow) where sleep is initiated late relative to the DLMO and might therefore be expected to increase exposure to phase-delaying light and minimize exposure to phase-advancing light. (B) Results of the melatonin suppression test; melatonin levels on the night of the test are represented by the black closed circles and line while melatonin levels from 24-hours prior are represented by the gray line. Light levels are plotted on the secondary y-axis on a log scale; yellow shading plots the timing and intensity of the bright light. (C) Percent wakefulness during forced desynchrony as a function of circadian phase (0° defined as the core body temperature minimum) and time-into-sleep episodes.

Figure 2. Participant 2.

(A) Single-raster plot of wrist actigraphy data from all 332 days of study (black denotes movement); hours are along the horizontal axis and days down the vertical axis. Red circles represent the timing of the salivary dim light melatonin onsets (DLMOs). (B–E) Double-raster plots (black bars denote sleep periods) of sleep diary data from selected days of study and highlight the different sleep-wake patterns observed. In (B) there is a non–24-hour sleep-wake schedule with an overall observed sleep-wake period of 24.7 hours (days 56–96). Note however that there was a week (days 74–81) when the observed sleep-wake period was 32.0 hours (black dashed line). The overall sleep-wake period and observed melatonin periods (red dashed line) were both 24.8 hours from days 73 to 95. (C) is an example of an irregular sleep-wake pattern, (D) shows a predominantly 24-hour sleep-wake pattern, and (E) shows again weeks where the observed sleep-wake period exceeded 30 hours (eg, 35.0 hours, days 210–217 and 39.8 hours, days 228–235).

Figure 3. Participant 3.

Double-raster plot of sleep diary data. Hours are along the horizontal axis and days down the vertical axis; 2 days are shown on each horizontal line. Self-selected sleep timing is represented by the black bars and hatched bars denote missing data. The red circle indicates the timing of the dim light melatonin onset.