Increased sensitivity of the circadian system to light in delayed sleep-wake phase disorder.

KEY POINTS: This is the first study to demonstrate an altered circadian phase shifting response in a circadian rhythm sleep disorder. Patients with delayed sleep-wake phase disorder (DSWPD) demonstrate greater sensitivity of the circadian system to the phase-delaying effects of light. Increased circadian sensitivity to light is associated with later circadian timing within both control and DSWPD groups. DSWPD patients had a greater sustained pupil response after light exposure. Treatments for DSWPD should consider sensitivity of the circadian system to light as a potential underlying vulnerability, making patients susceptible to relapse. ABSTRACT: Patients with delayed sleep-wake phase disorder (DSWPD) exhibit delayed sleep-wake behaviour relative to desired bedtime, often leading to chronic sleep restriction and daytime dysfunction. The majority of DSWPD patients also display delayed circadian timing in the melatonin rhythm. Hypersensitivity of the circadian system to phase-delaying light is a plausible physiological basis for DSWPD vulnerability. We compared the phase shifting response to a 6.5 h light exposure (∼150 lux) between male patients with diagnosed DSWPD (n = 10; aged 20.8 ± 2.3 years) and male healthy controls (n = 11; aged 22.4 ± 3.3 years). Salivary dim light melatonin onset (DLMO) was measured under controlled conditions in dim light (<3 lux) before and after light exposure. Correcting for the circadian time of the light exposure, DSWPD patients exhibited 31.5% greater phase delay shifts than healthy controls. In both groups, a later initial melatonin phase was associated with a greater magnitude phase shift, indicating that increased circadian sensitivity to light may be a factor that contributes to delayed phase, even in non-clinical groups. DSWPD patients also had reduced pupil size following the light exposure, and showed a trend towards increased melatonin suppression during light exposure. These findings indicate that, for patients with DSWPD, assessment of light sensitivity may be an important factor that can inform behavioural therapy, including minimization of exposure to phase-delaying night-time light.

Sleep and circadian instability in delayed sleep-wake phase disorder.

STUDY OBJECTIVES: In patients with delayed sleep-wake phase disorder (DSWPD), the circadian clock may be more easily affected by light at night. This creates a potential vulnerability, whereby individuals with irregular schedules may have less stable circadian rhythms. We investigated the stability of circadian timing and regularity of sleep in patients with DSWPD and healthy controls. METHODS: Participants completed 2 dim-light melatonin onset (DLMO) assessments approximately 2 weeks apart while keeping their habitual sleep/wake schedule. After the second DLMO assessment, light sensitivity was assessed using the phase-resetting response to a 6.5-hour 150-lux stimulus. The change in DLMO timing (DLMO instability) was assessed and related to light sensitivity and the sleep regularity index. RESULTS: Relative to healthy controls, patients with DSWPD had later sleep rhythm timing relative to clock time, earlier sleep rhythm timing relative to DLMO, lower sleep regularity index, and greater DLMO instability. Greater DLMO instability was associated with increased light sensitivity across all participants, but not within groups. CONCLUSIONS: We find that circadian timing is less stable and sleep is less regular in patients with DSWPD, which could contribute to etiology of the disorder. Measures of light sensitivity may be informative in generating DSWPD treatment plans.