Delayed sleep phase disorder: clinical perspective with a focus on light therapy

Figures & data

Figure 1 Model for eyelid transmittance proposed by Bierman et al. Figure adapted from Bierman A, Figueiro MG, Rea MS. Measuring and predicting eyelid spectral transmittance. J Biomed Optics. 2011;16(6):067011.⁸⁰ Copyright 2011 Society of Photo Optical Instrumentation Engineers. One print or electronic copy may be made for personal use only. Systematic electronic or print reproduction and distribution, duplication of any material in this paper for a fee or for commercial purposes, or modification of the content of the paper are prohibited. http://dx.doi.org/10.1117/1.3593151.

Figure 2 Flashing blue light mask used by older adults living at home.

Notes: Flashing light was delivered through closed eyelids during sleep. The blue light mask shown here contains two blue LED arrays (λ_max =480 nm, FWHM =24 nm), one for each eyelid. In the study, the light-stimulus condition was a train of blue or red light pulses: 2-second duration light pulses spaced apart 30 seconds, for no more than 3 hours, delivered before predicted minimum core body temperature. Photo courtesy of Lighting Research Center, Rensselaer Polytechnic Institute.⁹⁵
Abbreviations: LED, light emitting diode; FWHM, full width at half maximum.

Table 1 Studies investigating how light can be used to treat DSPD symptoms in the lab and in the field

Author	Year	Title	Objective	Participants	Methods/protocol	Results
Ando et al^Citation81	1999	Light mask 500 lux treatment for delayed sleep phase syndrome	To test, in the field, whether a light mask treatment, delivering light through eyelids during sleep advanced circadian markers in patients diagnosed with DSPD	Five participants meeting the criteria for DSPD experienced the active light and five experienced the placebo light	Participants were divided into two groups by bedtime before or after 2 am, based on the 2-week baseline sleep log data. Participants were then randomly assigned to the active (500 lux for 3 hours prior to awakening for 12 days) or the placebo light condition (0.1 lux light with the same timing). CBT and urinary 6-sulfatoxymelatonin were measured. Mood was assessed with the SIGH-SAD at baseline, during treatment, and immediately after treatment. Sleep logs were kept at all times	Slight, albeit not statistically significant phase advance of the body temperature rhythm and a slight phase delay of the melatonin rhythm. Both groups reported significant mood improvement
Appleman et al^Citation14	2013	Controlling light–dark exposure patterns, rather than sleep schedules, determines circadian phase	To study, in the field, the effects of differing light exposure timing on early and late sleepers, while placing participants on an advanced sleep schedule, and a delayed sleep schedule	21 participants who normally woke between 6.30 and 8 am, and who went to bed between 11 pm and 1.30 am	Participants collected baseline data for 5 days after which half of the participants received an advancing light pattern (2 hours of 470-nm light goggles in the morning and 3 hours of orange-tinted goggles in the evening), while the remaining participants received a delaying light pattern (3 hours of 470-nm light goggles in the evening and 2 hours of orange-tinted goggles in the morning) for 7 days. Participants were placed on a 1.5-hours advanced sleep–wake schedule. DLMO was collected at the end of baseline and intervention weeks	After 7 days of the light and sleep intervention, DLMO was significantly delayed and advanced respectively following the corresponding light treatment
Cole et al^Citation82	2002	Bright light mask treatment of delayed sleep phase syndrome	To test, in the field, whether a light mask treatment delivering light through closed eyelids during sleep would phase advance circadian rhythms in DSPD patients	54 participants. 28 were randomly assigned to the bright light group and 26 to the dim light group	Light masks delivering 2,700 lux at the surface of the closed eyelid (estimated corneal illuminance was 57 lux). For dim light treatment, corneal illuminance was 0.1 lux. Lights were turned on 4 hours prior to waking, ramped up for 1 hour, and stayed on at full brightness until participants got up	Intervention produced significantly earlier phases and earlier sleep onsets only among participants whose baseline 6-sulfatoxymelatonin acrophase was later than 6.02 am. Despite equal expectations at baseline, participants rated bright treatment as more effective than dim treatment
Crowley and Carskadon^Citation75	2010	Modifications to weekend recovery sleep delay circadian phase in older adolescents	To study, in the field, the effects of an extended weekend sleep period on the sleep–wake cycle in adolescents, (experiment 1) and to test whether a modified weekend sleep schedule or lighting treatment and extended weekend sleep could adjust and improve the sleep–wake cycle (experiment 2)	12 participants were included in experiment 1, and 33 participants were included in experiment 2	Experiment 1 was a 4-week, within-subjects counterbalanced design, which compared a “typical” weekend to a “nap” weekend. Each participant wore an actigraph. Experiment 2 was a follow-up to experiment 1, and was a 2-week between-subjects protocol with the two groups maintaining the identical sleep schedules and differing morning light exposure. The light group sat in front of an LED short-wavelength (454–484 nm) light box for 1 hour after awakening on Saturday and Sunday. Before Friday, and after Sunday, saliva samples were collected for DLMO for both experiments	Adolescents experienced a phase delay after keeping an extended weekend sleep schedule. Changing wake time or exposing participants to short-wavelength light therapy did not allow the adolescents’ circadian rhythm to stabilize in this study
Figueiro et al^Citation18	2014	The effects of chronotype, sleep schedule, and light–dark pattern exposures on circadian phase	To study, in the field, the effects of differing light exposure timing on early and late sleepers, while placing participants on a fixed sleep schedule	23 participants divided between self-reported early (n=12) and late (n=11) sleepers	Participants collected baseline data for 6 days, where they wore a light sensing device on their wrists. During the intervention weeks, half of the participants were randomly assigned to receive an advancing light pattern (2 hours of 470 nm light goggles in the morning and 3 hours of orange-tinted goggles in the evening) and the others received a delaying light pattern (3 hours of 470 nm light goggles in the evening and 2 hours of orange-tinted goggles in the morning). After a 3-week washout period, they were placed on the opposite protocol. The sleep–wake schedule was advanced by 1.5 hours on the intervention weeks. DLMO was collected at the end of baseline and intervention weeks	DLMO was significantly delayed and advanced respectively, following the corresponding light treatment. There were no significant differences in DLMO times between groups, but later chronotypes tended to delay more than earlier ones with the delaying light and earlier chronotypes tended to advance more than later chronotypes with the advancing light
Lack et al^Citation77	2007	Morning blue light can advance the melatonin rhythm in mild delayed sleep phase syndrome	To test, in the field, whether morning blue light exposure,administered via LEDs, can promote an advance of the melatonin rhythm and the sleep period in participants with mild DSPD	18 participants meeting the criteria for DSPD were recruited from a university population	The participants were randomly selected to receive 2 hours of 470 nm light upon awakening or a control intervention. Each participant kept a sleep–wake diary during baseline week. Wake times and exposure to blue light were gradually advanced each morning over the treatment week. The control group followed the same wake protocol, but they did not receive the morning blue light intervention. Participants self-selected their bedtimes. At the end of the week, saliva samples were collected to determine DLMO	DLMO was significantly advanced by 2.5 hours in the treatment group and remained the same in the control group. However, mean sleep onset time, wake time, and total sleep time were not significantly changed with the treatment. Sleep onset times were advanced by 70 minutes in the treatment group. Authors state that effective DSPD treatment may require adjunct behavioral instructions
Rosenthal et al^Citation73	1990	Phase-shifting effects of bright morning light as treatment for delayed sleep phase syndrome	To test, in the lab, whether patients with DSPD can have their circadian rhythms successfully phase advanced by a combination of morning bright light and late afternoon/evening light restriction	20 participants who met DSPD criteria: sleep onset after 1 am at least 4 nights per week, significant disruption of work/social relationships due to sleep patterns, and inability to be alert in the morning	In a crossover study, participants experienced an active treatment (2,500-lux full-spectrum light treatment for 2 hours between 6 and 9 am and dark goggles from 4 pm until dusk) and a control treatment (300-lux full-spectrum light for 2 hours between 6 and 9 am and clear goggles from 4 pm until dusk). After dusk, light was restricted to one or two bedside lamps for both conditions. The timing of awakening was kept constant. The CBT was measured every 5 minutes for a 24-hour period using a Vitalog monitor and thermistor. Multiple sleep latency tests were performed before and after each treatment condition	Participants rated the active intervention as being better, resulting in greater alertness and earlier sleep times than the control intervention. The active intervention significantly phase advanced circadian rhythms of CBT by approximately 1 hour 25 minutes compared to 10 minutes in the control condition. A significant increase in multiple sleep latencies were observed at 9 and 11 am during the active intervention compared to the control intervention
Sharkey et al^Citation17	2011	Effects of an advanced sleep schedule and morning short wavelength light exposure on circadian phase in young adults with late sleep schedules	To examine the effects of an advanced sleep/wake schedule and morning short wavelength (blue) light in 25 adults with late sleep schedules and subclinical features of DSPD	25 participants with late sleep schedules and subclinical features of DSPD	After a baseline week, participants kept individualized, 1- to 2.5-hour advanced, 7.5-hour sleep schedules for 6 days. Participants were randomly assigned to groups to receive “blue” (470 nm, ∼225 lux) or “dim” (<1 lux) light for 1 hour after waking each day. Head-worn Daysimeters measured light exposure; actigraphs and sleep diaries confirmed schedule compliance. At the end of the baseline and intervention weeks, participants returned to the lab to collect saliva samples for DLMO. Participants also filled out questionnaires probing their mood, depression, anxiety, and stress	After 6 days, both groups showed significant circadian phase advances, but morning blue light was not associated with larger phase shifts than dim-light exposure. No significant changes in mood, depression, anxiety, and stress were observed before and after the intervention. Authors conclude that a fixed, advanced schedule should be effective at advancing sleep and circadian phase in those suffering from DSPD
Watanabe et al^Citation74	1999	Effects of phototherapy in patients with delayed sleep phase syndrome	To examine, in the lab, the effects of short-term exposure to light therapy on PSG and CBT of DSPD patients	Six DSPD patients participated in the study	PSG was performed between bedtimes and natural awakening for 2 consecutive nights before light administration. After the baseline PSG, participants were given light therapy for 5 consecutive days. Light treatment was administered to each participant for 3 hours in the morning, starting 1.5 hours after the time of CBT nadir. CBT was sampled every 5 minutes using a rectal temperature probe and ambulatory temperature monitor for 10 days which included the periods of light therapy application and PSG measurements	Sleep onset time was significantly advanced by more than 2 hours and sleep offset time was significantly advanced by more than 3 hours. Total sleep time and amounts of stage 2 and rapid eye movement sleep from the PSG were reduced after light therapy. The timing of minimum CBT was advanced in all participants after the light therapy

Abbreviations: CBT, core body temperature; DLMO, dim light melatonin onset; DSPD, delayed sleep phase disorder; h, hour(s); LED, light-emitting diode; min, minute(s); PSG, polysomnography; SIGH-SAD, Structured Interview Guide for Hamilton Depression Rating Scale – Seasonal Affective Disorder version.

Figure 3 Correlation between DLMO and the predicted phase changes calculated from the Daysimeter data and the modified Kronauer model.

Notes: (A) Measured changes in dim light melatonin onset (DLMO) from baseline to postintervention are plotted on the ordinate and circadian stimulus (CS)-oscillator model predictions based on actual measured light exposures during the intervention are plotted on the abscissa. (B) Measured changes in DLMO from baseline to postintervention are plotted on the ordinate and CS-oscillator model predictions based solely on the treatment light exposures (ie, not using light exposures measured throughout the day by the Daysimeter) are plotted on the abscissa. The ideal fit was determined using the least square method, where the difference between the measured DLMO and the predicted DLMO was calculated.

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