The pupillary light reflex distinguishes between circadian and non-circadian delayed sleep phase disorder (DSPD) phenotypes in young adults

McGlashan, Elise M.; Burns, Angus C; Murray, Jade M.; Sletten, Tracey L.; Magee, Michelle; Rajaratnam, Shanthakumar M W; Cain, Sean W.

doi:10.1371/journal.pone.0204621

Cited by 23 publications

(14 citation statements)

References 30 publications

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“…In our study, the association between higher non‐visual sensitivity to light and later circadian phase in late sleepers was measured with a laboratory test of melatonin suppression (Moderie, Van der Maren, & Dumont, ). That association was also found in recent studies on patients with delayed sleep–wake phase disorder (DSWPD), using other non‐visual responses to light such as light‐induced circadian phase shifts (Watson et al., ) and the pupillary light reflex (McGlashan et al., ). The association between light sensitivity and circadian phase suggests that indoor lighting at home may have a larger suppressing effect on melatonin secretion in individuals with a late sleep schedule, particularly those with a late circadian phase.…”

Section: Introductionsupporting

confidence: 61%

“…Melatonin suppression before bedtime was larger in delayed participants with a later DLMO, which is consistent with our previous observation of an association between non‐visual sensitivity to light and circadian phase in these subjects (Moderie et al., ). An association between non‐visual sensitivity to light and circadian phase is also supported by recent studies on DSWPD patients (McGlashan et al., ; Watson et al., ). Increased non‐visual sensitivity to light seems therefore to be an aetiological factor in the complaint of a delayed sleep schedule in “circadian” sleep‐delayed individuals.…”

Section: Discussionmentioning

confidence: 52%

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Home versus laboratory assessments of melatonin production and melatonin onset in young adults complaining of a delayed sleep schedule

Moderie

Maren

Paquet

et al. 2019

Journal of Sleep Research

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Recent evidence points toward an association between higher non‐visual sensitivity to light and a later circadian phase in young adults complaining of a delayed sleep schedule. Light exposure in the evening may therefore induce a larger suppression of melatonin production in these individuals, which might: (a) bias home estimates of melatonin onset; and (b) decrease sleep propensity at bedtime. In this study, we compared home and laboratory melatonin onsets and production in sleep‐delayed and control participants, using saliva samples collected in the 3 hr preceding habitual bedtime. The mean light intensity measured during saliva sampling at home was ~10 lux in both groups. Melatonin suppression at home was significant, averaging 31% and 24% in sleep‐delayed and control individuals, respectively. Group difference in melatonin suppression was not significant. Estimates of melatonin onset were on average 27 min later at home than in laboratory conditions, with no group difference. Looking specifically at sleep‐delayed participants, there was no correlation between non‐visual sensitivity to light and home–laboratory differences in melatonin onsets. However, higher light sensitivity was associated with greater melatonin suppression in the hour before habitual bedtime. Greater melatonin suppression before bedtime was also associated with a later circadian phase. These results indicate that the validity of home estimates of melatonin onset is similar in sleep‐delayed and in control individuals. Results also suggest that increased non‐visual sensitivity to light could impact melatonin secretion in sleep‐delayed individuals and contribute to a late bedtime by delaying circadian phase and decreasing sleep propensity.

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Section: Introductionsupporting

confidence: 61%

Section: Discussionmentioning

confidence: 52%

Home versus laboratory assessments of melatonin production and melatonin onset in young adults complaining of a delayed sleep schedule

Moderie

Maren

Paquet

et al. 2019

Journal of Sleep Research

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“…Patients with SAD may also exhibit seasonal hyposensitivity to light, suggesting that abnormally high or low light sensitivity may be associated with pathology (35). Methods to efficiently phenotype an individual’s light sensitivity [e.g., by using melatonin suppression or pupillary measures (36)] will likely be needed to develop personalized interventions based on an individual’s circadian physiology.…”

Section: Discussionmentioning

confidence: 99%

High sensitivity and interindividual variability in the response of the human circadian system to evening light

Phillips

Vidafar

Burns

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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291

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Before the invention of electric lighting, humans were primarily exposed to intense (>300 lux) or dim (<30 lux) environmental light—stimuli at extreme ends of the circadian system’s dose–response curve to light. Today, humans spend hours per day exposed to intermediate light intensities (30–300 lux), particularly in the evening. Interindividual differences in sensitivity to evening light in this intensity range could therefore represent a source of vulnerability to circadian disruption by modern lighting. We characterized individual-level dose–response curves to light-induced melatonin suppression using a within-subjects protocol. Fifty-five participants (aged 18–30) were exposed to a dim control (<1 lux) and a range of experimental light levels (10–2,000 lux for 5 h) in the evening. Melatonin suppression was determined for each light level, and the effective dose for 50% suppression (ED50) was computed at individual and group levels. The group-level fitted ED50 was 24.60 lux, indicating that the circadian system is highly sensitive to evening light at typical indoor levels. Light intensities of 10, 30, and 50 lux resulted in later apparent melatonin onsets by 22, 77, and 109 min, respectively. Individual-level ED50 values ranged by over an order of magnitude (6 lux in the most sensitive individual, 350 lux in the least sensitive individual), with a 26% coefficient of variation. These findings demonstrate that the same evening-light environment is registered by the circadian system very differently between individuals. This interindividual variability may be an important factor for determining the circadian clock’s role in human health and disease.

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“…Current approaches to measuring circadian light sensitivity-either via phase shifting or melatonin suppression-also require extended lab visits. However, pupillary measures may provide a more rapid assessment of circadian light sensitivity (Roecklein et al, 2013;Adhikari et al, 2015;Van Der Meijden et al, 2016;McGlashan et al, 2018a;Bullock et al, 2019), which would be suitable for optimizing model parameters. We note, however, that these studies do not directly link pupillary responses to shifts in circadian phase.…”

Section: Discussionmentioning

confidence: 99%

The Role of Light Sensitivity and Intrinsic Circadian Period in Predicting Individual Circadian Timing

et al. 2020

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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 ( n = 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 ( p), (2) a parameter determining the shape of the phase-response curve to light ( K), and (3) the intrinsic circadian period ( tau). 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 p, 4.28 h for K, and 3.26 h for tau. 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 p, 0.53 h for K, and 0.42 h for tau. Fitting p and K 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.

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The pupillary light reflex distinguishes between circadian and non-circadian delayed sleep phase disorder (DSPD) phenotypes in young adults

Cited by 23 publications

References 30 publications

Home versus laboratory assessments of melatonin production and melatonin onset in young adults complaining of a delayed sleep schedule

Home versus laboratory assessments of melatonin production and melatonin onset in young adults complaining of a delayed sleep schedule

High sensitivity and interindividual variability in the response of the human circadian system to evening light

The Role of Light Sensitivity and Intrinsic Circadian Period in Predicting Individual Circadian Timing

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