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. 2018 Dec;596(24):6249-6261.
doi: 10.1113/JP275917. Epub 2018 Oct 25.

Increased Sensitivity of the Circadian System to Light in Delayed Sleep-Wake Phase Disorder

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Free PMC article

Increased Sensitivity of the Circadian System to Light in Delayed Sleep-Wake Phase Disorder

Lauren A Watson et al. J Physiol. .
Free PMC article

Abstract

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.

Keywords: Circadian rhythm; DSPD; light; phase shift.

Figures

Figure 1
Figure 1
Flow chart of participant numbers and excluded participants at each step of the screening process
Figure 2
Figure 2. Raster plot of an example study protocol from home DLMO to discharge based on a HC participant with a bedtime of ∼23.00 h and DLMO of ∼20.00 h
Sleep periods are denoted in black, dim‐light conditions in light grey and constant routine procedures in dark grey; ○ denotes home DLMO time, which was used to time the start of the in‐laboratory light exposure. [Color figure can be viewed at wileyonlinelibrary.com]
Figure 3
Figure 3
The range of light onset timing compared to the CR 1 DLMO for both healthy controls and DSWPD patients [Color figure can be viewed at wileyonlinelibrary.com]
Figure 4
Figure 4. Larger circadian phase shifting is observed in DSWPD group than control group
A, individual datapoints for phase shift (y‐axis) vs. circadian timing of the light exposure based on DLMO (x‐axis), showing Control (blue circles) and DSWPD (red triangles). The black curve shows the predicted phase shift, using the phase response curve (PRC) from Khalsa et al. (2003), rescaled by a factor of 1.61 to match our lower brightness stimulus (150 vs. 9500 lux), based on the human dose response curve to light published in Zeitzer et al. (2000). Plotting uses the convention from Khalsa et al. (2003), where circadian time of 22.00 h represents the melatonin midpoint. B, relative phase shifts are plotted for each individual, defined as the actual phase shift divided by the predicted phase shift from panel A. A significant group difference is found between DSWPD and controls (P < 0.05). In both panels, dark grey shading represents within 15% of predicted and light grey shading represents within 30% of predicted. [Color figure can be viewed at wileyonlinelibrary.com]
Figure 5
Figure 5. Relationships between melatonin midpoint and relative phase shift for both DSWPD patients and healthy controls
Dashed lines show predictions from the mixed‐effects model. [Color figure can be viewed at wileyonlinelibrary.com]
Figure 6
Figure 6. The difference in percentage of melatonin suppression between groups
The dotted line denotes average suppression to 150 lux lighting from Zeitzer et al. (2000). [Color figure can be viewed at wileyonlinelibrary.com]
Figure 7
Figure 7. The mean and SEM of static pupil size for each group before, during and after the 6.5 h light exposure period
Statistical significance: * P < 0.05 and ** P <0.01 for time effect, #P < 0.05 for the time × group effect. [Color figure can be viewed at wileyonlinelibrary.com]

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