Circadian Rhythms in Children and Adolescents

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Circadian Rhythms in Children and Adolescents Sarah Morsbach Honaker, Ph.D., CBSM Assistant Professor of Pediatrics IU School of Medicine Society for Behavioral Sleep Medicine Practice and Consultation Webinar March 28, 2018

Objective and Outline Objective Assess DSWPD in adolescents Apply treatment strategies for adolescents w/ DSWPD Outline Adolescent Sleep Overview DSWPD: Assessment and Treatment in Adolescents

Biology of Sleep: Two Process Model of Sleep Regulation Borbély AA; Hum Neurobiol 1982;1(3):195-204. Sleep/Wake Homeostasis Circadian Rhythms

Circadian Phase Across Development

Phase Delay Associated with Tanner Stage Caraskadon MA & Acebo C, NYAS 2004

Carskadon Pediatr Clin N Am 2011;58:637-647.

Sleep in the Modern American Family National Sleep Foundation 2014 Poll Parental Report of Sleep Duration on School Nights 7 hours or less 8 hours 9 hours or more 80% 70% 60% 50% 40% 30% 20% 10% 0% 69% 56% 42% 29% 29% 34% 23% 8% 10% 6-11 years 12-14 years 15-17 years Age Group Sampled 1,103 caregivers with a child aged 6-17

Sleep in the Modern American Family National Sleep Foundation 2014 Poll Estimated average sleep duration on school nights by sleep-related rules Parent says he/she: Has rules about Does not have rules about Bedtime 8.4 7.3 Television 8.3 7.7 Caffeine 9.3 7.7 Smartphone or cell phone 8.2 7.9 Computer/tablet 8.3 7.8 Video games 8.3 7.8 Parent says he/she: ALWAYS ENFORCES rules about DOESN T ALWAYS ENFORCE rules about Bedtime 8.5 8.1 Television 8.6 8.0 Caffeine 8.7 7.8 Smartphone or cell phone 8.6 7.8 Computer/tablet 8.6 7.9 Video games 8.5 7.9

The Role of School Start Times

School Start Times: Key Findings Later school start times result in increased nocturnal sleep, ranging 45 min. to 1 hour 1-3 Improvements in tardiness/attendance 3 Better academic performance 1 Reduced daytime sleepiness 1,3 Improved mood 1 Increased overall health and healthy behaviors 123 Decreased automobile crash rate 2 1Wahlstrom K et al. CAREI Report 1998 2Danner FA & Phillips B. J Clin Sleep Med 2008:4; 533-535. 3Owens JA et al. Arch Ped Adol Med 2010:164;608-614.

AAP Recommendation: Delay School Start Time until 8:30 am or Later Pediatrics 2014;134:642-649.

Assessing Circadian Rhythms Clinical Interview Sleep-wake patterns Phase preference Sleep Diary Actigraphy Validated Measures Phase markers

Sleep Patterns - Gavin Weekday Weekend Bedtime 10:00 pm When tired (~2am) Sleep Onset Latency 2-3 hours <30 minutes Number of Night wakings 0 0 Total Time Awake during Nightwakings NA NA Wake time 6:00 am 12-1pm Naps 1-2x/wk (2 hrs) NA Total Sleep Time 6-7 hours + NAP 9.5-10.5 hours

Assessing Circadian Phase Disturbance Key QuestionS What is your preferred sleep schedule? Do you have [presenting problem] when sleeping on your preferred schedule?

Why Can t You Sleep? Alternate activities? Light exposure? Leg discomfort? Anxiety? Not tired? Fears? 49% of adolescents report nightime fears 1 1 Gordon J et al. Behav Res Ther. 2007;45:2464-72.

Sleep Diary - Gavin

Chronotype Measure Age Items Report Domains/Subscales Children s ChronoType Questionnaire Werner H et al. Chronobiol Int 2009;26:992-1014. Children s Morningness- Eveningness Scale Carksadon et al. Sleep 1993;16(3):258-262. 4-11 27 Parent; no specified time frame 4 th grade and older 10 Self; no specified time frame Midsleep Point Morningness/Eveningness Chronotype Total score

Circadian Phase Markers Core body temperature Melatonin Cortisol Urinary 6-sulfatoxymelatonin

Comorbid Insomnia? Insomnia Threshold ---------------------------------------------------------------------------------------------------------------------------------------------- DSWPD as Precipitating Factor? Pre-morbid Acute Early Chronic Short Term Long Term Predisposing Precipitating Perpetuating Conditioned Arousal

Delayed Sleep Wake Phase Disorder

Delayed Sleep Wake Phase Disorder (DSWPD) A: Significant delay in the phase of the major sleep episode in relation to the desired or required sleep time and wake-up time B: Symptoms present at least 3 months C: When patients choose their own schedule, they exhibit improved sleep quality and duration and maintain a delayed phase D: Sleep log/actigraphy for at least seven days demonstrate a delay in the timing of the habitual sleep period. E: Sleep disturbance is not better explained by another disorder or medication use. International Classification of Sleep Disorders 3 rd Ed, 2014 [ICSD-3]

DSWPD Prevalence rates 7-16% among adolescents and young adults Positive family history reported in ~40% of those with DSWPD Higher prevalence in those with ADHD, ASD Typical sleep onset 1-6am Inappropriate timing of light exposure as a perpetuating factor International Classification of Sleep Disorders 3 rd Ed, 2014 [ICSD-3]

Proposed Etiology Longer than average intrinsic circadian period Abnormalities in the light phase response curve, such as hypersensitivity to evening light 1 Diminished ability to compensate for sleep deprivation 2 Genetic contribution (Polymorphism in circadian genes) Behavioral preferences 1 Ozaki S et al. Sleep 1996;19:36-40. 2 Uchiyama M et al. Sleep 2000;23:553-8.

DSWPD Clinical Practice Guidelines Auger RR et al. JCSM 2015;11(10):1199-1236. Use of strategically timed melatonin: WEAK FOR Adults with and without depression Children and adolescents (no comorbidities) Children adolescents with comorbid psychiatric conditions Use of post-awakening light therapy in conjunction with behavioral treatments: WEAK FOR Children and adolescents NO RECOMMENDATION (Insufficient or no evidence) for: wakefulness-promoting medications Oral vitamin B12 Novel forms of light therapy (other than a light box)

DSWPD Treatment: Chronotherapy Based on premise of timing (and not light) as main synchronizer of circadian system Consider when delay >3h Delay sleep period (BT & WT) 2-3 hours per day until target schedule is reached Typical duration: 6-7 days Example: Day 1 4am-12pm; Day 2 7am-3pm; Day 3 10am-6pm; Day 4 1pm-9pm; Day 5 4pm-12am; Day 6 7pm-3am; Day 7 10pm-6am Relapse is common 1 1 Ito A et al. Jpn J Psychiat Neur 1993;47:563-7.

DSWPD Treatment: Advancing Circadian Rhythm Gradually advancing schedule E.g. 15-30 minutes per day Timed Light Exposure Morning light exposure, usually 30-60 minutes depending on type of light, lux, and distance from patient Exogenous Melatonin Administered afternoon or evening as a phase shifter, usually at low doses (e.g. 0.1-0.5mg)

Light and the Circadian Timing System The point of singularity is at the circadian nadir, around the minimal core body temperature. (after 2/3 of the night or 2 hours prior to wake time) Light exposure prior to that point has a phase delay effect. Light exposure after that point has a phase advance effect.

3 days of Baseline Sample DSWPD Schedule Chronotherapy - Advance Melatonin (0.5 mg) Bedtime Waketime Light Therapy 7-8pm 1 am 10am 10-10:30am Day 4 6:30-7:30pm 12:30pm 9:30am 9:30-10:30am Day 5 6-7pm 12pm 9am 9-9:30 am Day 6 5:30-6:30pm 11:30pm 8:30am 8:30-9:am Etc. Target 4-5pm 10pm 7:00 am 7-7:30am Other considerations: Diary/actigraphy for adherence; letter to school; create maintenance schedule once target is reached; dim light 2 hrs. prior to BT; also can give Melatonin 15-30 min. prior to BT

Using Technology to Minimize Evening Blue Light Exposure f.lux Orange-tinted glasses Manually reduce brightness Android apps: neyetlight & screen filter Removable orange light screen filter Word processing: use a black background with white letters

DSWPD Treatment: Maintenance D/c Melatonin resulted in return to delayed schedule in majority of cases in studies where melatonin was primary treatment 1-2 Once schedule has been advanced to target, on-going melatonin and/or light therapy may be recommended to maintain entrainment 1 Dahlitz M et al. Lancet 1991;337:1121-4. 2 Dagan Y et al. Chronobiol 1998;15:181-90.

DSWPD: Maximizing Compliance Consider starting with improvements in sleep hygiene Assess motivation and feasibility prior to choosing treatment option Systems to support compliance are crucial: WAKETIMES: Consider multiple alarms; an adult verifying that pt. is awake (in person or electronically); planned activities after waketime BEDTIMES: Plan for maintaining wakefulness if sleepy during wake period ELECTRONICS: Guidelines around electronic-free window prior to bedtime. Provider note to school/work regarding missed obligations

DSPS & Melatonin Meta-Analysis van Geijlswijk et al. Sleep 2010;33(12):1605-1614. Examined studies using melatonin to advance CRs in DSWPD (91 adults; 226 children) Exogenous melatonin advanced mean endogenous melatonin onset by 1.18 hours; decreased SOL by 23.27 minutes Duration range: 10 days 4 weeks Dose range: 0.3mg-6mg Timing range: 17:15-22:00 Very few adverse events reported: HA most frequent

Are Light and Melatonin Necessary? Saxvig IW et al. Chrono Int 2014;31(1):72-86 Examined a DSWPD treatment protocol on n=40 adolescents and adults Melatonin / Bright light Placebo / Bright light Melatonin / Low light Placebo / Low light All groups improved after 2 weeks but no differences between treatment groups Gains maintained at 3 months only for those who continued sleep scheduling recommendations

Saxvig IW et al. Chrono Int 2014;31(1):72-86

Let Them Sleep!

Adolescent Sleep Health Appropriate light exposure Consistency between weekdays and weekends Circadian Alignment Parental limitsetting