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Transcript of 07/06/12© M.A. Carskadon 1 Why Do Teens Sleep Too Little? Biology and Society Mary A. Carskadon,...
![Page 1: 07/06/12© M.A. Carskadon 1 Why Do Teens Sleep Too Little? Biology and Society Mary A. Carskadon, PhD Sleep for Science Research Lab EP Bradley Hospital.](https://reader035.fdocuments.in/reader035/viewer/2022062519/56649ceb5503460f949b6e85/html5/thumbnails/1.jpg)
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Why Do Teens Sleep Too Little? Biology and Society
Mary A. Carskadon, PhD
Sleep for Science Research Lab
EP Bradley Hospital
Alpert Medical School of Brown University
Providence, RI
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Overview• Examine adolescent sleep behavior
• Review developmental changes of sleep-wake regulation
• Identify other factors that constrain teen sleep
• Introduce some behavioral challenges of insufficient sleep
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Adolescent Sleep Behavior
• Bedtime becomes later
• Rise time becomes earlier (school dependent)
• Total amount of sleep is reduced
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Adolescent Sleep Behavior
Sleep Variable
Sixth Seventh Eighth Ninth Tenth Eleventh Twelfth
SchoolNights
Bedtime 2124 2152 2153 2215 2232 2251 2302
Risetime 0642 0635 0636 0628 0623 0623 0631
Hrs Slept 8.4 8.1 8.1 7.6 7.3 7.0 6.9
Weekends
Bedtime 2231 2305 2326 2353 0003 0025 0045
Risetime 0853 0912 0921 0954 0954 1006 0951
Hrs Slept 9.2 8.9 9.0 8.8 8.9 8.8 8.4
National Sleep Foundation, Sleep in America Poll, 2006
8.38.3 7.67.6 6.66.6 5.45.4
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Adolescent Sleep Behavior
Sleep Variable
Sixth Seventh Eighth Ninth Tenth Eleventh Twelfth
SchoolNights
Bedtime 2124 2152 2153 2215 2232 2251 2302
Risetime 0642 0635 0636 0628 0623 0623 0631
Hrs Slept 8.4 8.1 8.1 7.6 7.3 7.0 6.9
Weekends
Bedtime 2231 2305 2326 2353 0003 0025 0045
Risetime 0853 0912 0921 0954 0954 1006 0951
Hrs Slept 9.2 8.9 9.0 8.8 8.9 8.8 8.4
National Sleep Foundation, Sleep in America Poll, 2006
8.38.3 7.67.6 6.66.6 5.45.4
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Adolescent Sleep Behavior
Sleep Variable
Sixth Seventh Eighth Ninth Tenth Eleventh Twelfth
SchoolNights
Bedtime 2124 2152 2153 2215 2232 2251 2302
Risetime 0642 0635 0636 0628 0623 0623 0631
Hrs Slept 8.4 8.1 8.1 7.6 7.3 7.0 6.9
Weekends
Bedtime 2231 2305 2326 2353 0003 0025 0045
Risetime 0853 0912 0921 0954 0954 1006 0951
Hrs Slept 9.2 8.9 9.0 8.8 8.9 8.8 8.4
National Sleep Foundation, Sleep in America Poll, 2006
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Adolescent Sleep Behavior
Sleep Variable
Sixth Seventh Eighth Ninth Tenth Eleventh Twelfth
SchoolNights
Bedtime 2124 2152 2153 2215 2232 2251 2302
Risetime 0642 0635 0636 0628 0623 0623 0631
Hrs Slept 8.4 8.1 8.1 7.6 7.3 7.0 6.9
Weekends
Bedtime 2231 2305 2326 2353 0003 0025 0045
Risetime 0853 0912 0921 0954 0954 1006 0951
Hrs Slept 9.2 8.9 9.0 8.8 8.9 8.8 8.4
National Sleep Foundation, Sleep in America Poll, 2006
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Adolescent Sleep Behavior
Sleep Variable
Sixth Seventh Eighth Ninth Tenth Eleventh Twelfth
SchoolNights
Bedtime 2124 2152 2153 2215 2232 2251 2302
Risetime 0642 0635 0636 0628 0623 0623 0631
Hrs Slept 8.4 8.1 8.1 7.6 7.3 7.0 6.9
Weekends
Bedtime 2231 2305 2326 2353 0003 0025 0045
Risetime 0853 0912 0921 0954 0954 1006 0951
Hrs Slept 9.2 8.9 9.0 8.8 8.9 8.8 8.4
National Sleep Foundation, Sleep in America Poll, 2006
22422242 23122312 00000000 00540054
Yang et al., Pediatrics, 2005 (Korean Teens)Yang et al., Pediatrics, 2005 (Korean Teens)
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Adolescent Sleep Behavior
Sleep Variable
Sixth Seventh Eighth Ninth Tenth Eleventh Twelfth
SchoolNights
Bedtime 2124 2152 2153 2215 2232 2251 2302
Risetime 0642 0635 0636 0628 0623 0623 0631
Hrs Slept 8.4 8.1 8.1 7.6 7.3 7.0 6.9
Weekends
Bedtime 2231 2305 2326 2353 0003 0025 0045
Risetime 0853 0912 0921 0954 0954 1006 0951
Hrs Slept 9.2 8.9 9.0 8.8 8.9 8.8 8.4
National Sleep Foundation, Sleep in America Poll, 2006
07180718 07000700 06480648 06180618
Yang et al., Pediatrics, 2005 (Korean Teens)Yang et al., Pediatrics, 2005 (Korean Teens)
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Adolescent Sleep Behavior
Sleep Variable
Sixth Seventh Eighth Ninth Tenth Eleventh Twelfth
SchoolNights
Bedtime 2124 2152 2153 2215 2232 2251 2302
Risetime 0642 0635 0636 0628 0623 0623 0631
Hrs Slept 8.4 8.1 8.1 7.6 7.3 7.0 6.9
Weekends
Bedtime 2231 2305 2326 2353 0003 0025 0045
Risetime 0853 0912 0921 0954 0954 1006 0951
Hrs Slept 9.2 8.9 9.0 8.8 8.9 8.8 8.4
National Sleep Foundation, Sleep in America Poll, 2006
8.38.3 7.67.6 6.66.6 5.45.4
Yang et al., Pediatrics, 2005 (Korean Teens)Yang et al., Pediatrics, 2005 (Korean Teens)
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• Converging evidence indicates that optimal sleep for the average adolescent may be 9+ hours
• National Sleep Foundation borderline sleep = 8-9 hours
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Discrepancy
Adolescent sleep need, therefore, does not appear to parallel sleep obtained for many teens.
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Factors that Underlie the Discrepancy
• Developmental changes in sleep regulation– Circadian timing system– Sleep wake homeostasis
• Developmental changes in psychosocial context
• Parents and schools
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Two-Process Model of Sleep Regulation (Borbély, 1982)
Process C: Circadian Rhythm
Process S: Sleep/Wake Homeostasis (sleep pressure)
Borbély & Achermann, 2000
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What developmental changes occur to the circadian timing
system?
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Circadian Regulation Changes: Measures to Assess Process C
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Circadian Regulation Changes: Measures to Assess Process C
• Phase preference—when do you prefer to be active, sleeping, etc?
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Circadian Regulation Changes: Measures to Assess Process C
• Phase preference—when do you prefer to be active, sleeping, etc?
• Phase of circadian rhythms—what time is it in your brain?
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Circadian Regulation Changes: Measures to Assess Process C
• Phase preference—when do you prefer to be active, sleeping, etc?
• Phase of circadian rhythms—what time is it in your brain?
• Period of the circadian timing system—what is the internal day length?
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Circadian Regulation Changes: Measures to Assess Process C
• Phase preference—when do you prefer to be active, sleeping, etc?
• Phase of circadian rhythms—what time is it in your brain?
• Period of the circadian timing system—what is the internal day length?
• Phase response to light—does light work the same across adolescence?
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Animals with Adolescent Phase Delay
• Homo sapiens (humans)
• Macca mulatta (Rhesus monkeys)
• Octodon degus (degu) [some ?]
• Rattus norvegicus (laboratory rat)
• Mus musculus (laboratory mouse)
• Psammomys obesus (fat sand rat)
Hagenauer et al., Devel Neurosci, 2009
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Phase Delay in Adolescent Humans
• Chronotype
• Circadian phase
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Chronotype and Adolescence
Roenneberg et al., Current Biol., 2004
• European sample• Time of midsleep on
“free” days• Delay is marked across
the 2nd decade• Is the inflection a
“biological marker for the end of adolesence?”
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Melatonin Onset (DLMO) Phase and Puberty Stage
19
20
21
22
23
Mel
aton
in O
nset
Tim
e
1 2 3 4 5
Tanner Stage
Carskadon et al. NYAS, 2004
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What might cause phase delay?
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What might cause phase delay?
• Changes in light exposure – Staying up later // more late light– Waking up later // less morning light
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What might cause phase delay?
• Changes in light exposure – Staying up later // more late light– Waking up later // less morning light
• Change in phase-dependent sensitivity to light exposure
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What might cause phase delay?
• Changes in light exposure – Staying up later // more late light– Waking up later // less morning light
• Change in phase-dependent sensitivity to light exposure
• Lengthening of intrinsic circadian period (i.e., longer internal day length)
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Exaggerated phase delay to light in pubertal female mice
Hagenauer et al., Devel Neurosci, 2001; after Weinert & Kompaeurova, Zoology, 1998
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0
2
4
6
8
23.6 23.8 24.0 24.2 24.5 24.7
Intrinsic Period
Adolescents
Adults
#
Intrinsic Circadian Period: Adolescents vs. Adults
Carskadon & Acebo Sleep, 2005
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Circadian Rhythms Summary
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Circadian Rhythms Summary
• Phase delays during adolescence– Phase preference is later– Melatonin phase is later
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Circadian Rhythms Summary
• Phase delays during adolescence– Phase preference is later– Melatonin phase is later
• Phase-dependent light sensitivity may change
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Circadian Rhythms Summary
• Phase delays during adolescence– Phase preference is later– Melatonin phase is later
• Phase-dependent light sensitivity may change
• Intrinsic period may lengthen
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Circadian Rhythms Summary
• Phase delays during adolescence– Phase preference is later– Melatonin phase is later
• Phase-dependent light sensitivity may change
• Intrinsic period may lengthen
• Result: Late nights are favored (so, too, late mornings)
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What developmental changes occur to the sleep-wake
homeostasis (sleep pressure) system?
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The “look” of sleep changes
Tarokh & Carskadon, Encyclopedia of Neuroscience, 2009
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Measures of Process S
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Measures of Process S
• Slow wave (NREM stages 3+4) sleep [qualitative: Deep sleep]
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Measures of Process S
• Slow wave (NREM stages 3+4) sleep [qualitative: Deep sleep]
• Slow-wave activity (SWA) in sleep [quantitative: Slow EEG waves]
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Measures of Process S
• Slow wave (NREM stages 3+4) sleep [qualitative: Deep sleep]
• Slow-wave activity (SWA) in sleep [quantitative: Slow EEG waves]
• Sleep propensity (speed of falling asleep)
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Changes of Slow Wave Sleep and Slow Wave Activity (SWA)
Jenni & Carskadon, Sleep, 2004
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Changes of Slow Wave Sleep and Slow Wave Activity (SWA)
Jenni & Carskadon, Sleep, 2004
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Changes of Slow Wave Sleep and Slow Wave Activity (SWA)
Jenni & Carskadon, Sleep, 2004
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Across pubertal development, SWA accumulation rate changes
7.7 h
13.5 h
3.0 h
2.9 h
Tanner Stages 1/2 Tanner Stage 5
Jenni, Achermann & Carskadon Sleep, 2005
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Across pubertal development, SWA accumulation rate changes
7.7 h
13.5 h
3.0 h
2.9 h
td = 2.8 h td = 2.7 hDecay Time Constant
Tanner Stages 1/2 Tanner Stage 5
Jenni, Achermann & Carskadon Sleep, 2005
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Across pubertal development, SWA accumulation rate changes
Jenni, Achermann & Carskadon Sleep, 2005
7.7 h
13.5 h
3.0 h
2.9 h
td = 2.8 h td = 2.7 hDecay Time Constantti = 8.9 h ti = 12.1 hRise Time Constant
Tanner Stages 1/2 Tanner Stage 5
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Model of Process S in Development
Jenni & LeBourgeois Curr Op Psychiatry, 2006
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Response to extended wakefulness during pubertal development
Taylor et al., J Sleep Res, 2005
Hours Awake
2.5 6.5 10.5 14.5 18.5 22.5 26.5
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Response to extended wakefulness during pubertal development
Taylor et al., J Sleep Res, 2005
Hours Awake
2.5 6.5 10.5 14.5 18.5 22.5 26.5
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Summary of Process S Change
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Summary of Process S Change
• Recovery sleep process does not change across adolescence– Need for sleep is stable
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Summary of Process S Change
• Recovery sleep process does not change across adolescence– Need for sleep is stable
• Accumulation of sleep pressure slows– Staying awake longer is easier
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Summary of Process S Change
• Recovery sleep process does not change across adolescence– Need for sleep is stable
• Accumulation of sleep pressure slows– Staying awake longer is easier
• Result: Late nights are easier to achieve, but the same amount of sleep is needed
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Psychosocial Context
• Exertion of autonomy
• Employment
• Substances
• ‘Screen time’ at night
• Social networking at night
• New loves and loves lost
• Et cetera, et cetera, et cetera
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Psychosocial Context: Electronic Media
Cain & Gradisar, Sleep Med, 2010
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Psychosocial Context: Electronic Media
Cain & Gradisar, Sleep Med, 2010
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Psychosocial Context: Electronic Media
Cain & Gradisar, Sleep Med, 2010
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Psychosocial Context: Electronic Media
Cain & Gradisar, Sleep Med, 2010
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Parents & Schools
• Lack of parent-set bedtime // sleep and sleepiness (Short et al., Sleep, 2011)
• Lack of parent-set bedtime // depression and suicidality (Gangwisch et al., Sleep, 2010)
• School start time: Earlier morning // less sleep // more sleepiness
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Sleep Is For
Slackers
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• 10th graders• Start time = 0720• Sleeping about 7
hours a night
Carskadon et al. Sleep, 1998
0
5
10
15
20
Sle
ep L
aten
cy
(mea
n+se
min
utes
)0830 1030 1230 1430
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0
10
20
30
40
0830 1030 1230 1430
Per
cent
age
of T
ests
w
ith R
EM
Sle
epREM occurred in 12 of 25
subjects—most in the morning
Carskadon et al. Sleep, 1998
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1800
1900
2000
2100
2200
2300
2400T
ime
of D
LSM
O
No REM REM
p =.027
Carskadon et al. Sleep, 1998
Circadian timing affected Circadian timing affected REM sleep, tooREM sleep, too
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Summary
• Sleep patterns change across adolescence
• Most teens sleep less than they need
• Most teens have irregular sleep schedule
• Many teens are in school too early
• Many teens are in school too underslept
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Carskadon, Pediatr Clin North Am, 2011
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Carskadon, Pediatr Clin North Am, 2011
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Carskadon, Pediatr Clin North Am, 2011
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Carskadon, Pediatr Clin North Am, 2011
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Carskadon, Pediatr Clin North Am, 2011
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Carskadon, Pediatr Clin North Am, 2011
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Carskadon, Pediatr Clin North Am, 2011
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Carskadon, Pediatr Clin North Am, 2011
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Summary of Effects of Insufficient Sleep
in Susceptible Teens
• Excessive sleepiness
• Impaired learning
• Impaired behavior regulation
• Poor mood, depression
• Appetite and metabolic changes; possible association with weight gain, obesity, diabetes risk
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AcknowledgementsCollaborators/FellowsRon Seifer, PhDJudy Owens, MD Amy Wolfson, PhDOskar G. Jenni, MDPeter Achermann, PhDMonique Lebourgeois, PhDDaniel Taylor, PhDLeila Tarokh, PhDEliza Van Reen, PhDStephanie Crowley, PhDKatherine Sharkey, MD, PhDJohn McGeary, PhDValerie Knopik, PhDKay Orzech, PhDBrandy Roane, PhD
Research AssistantsDave BushnellMaggie Gordon-FogelsonJena BurgnerGretchen SurhoffErin CampopianoJames Bass
Lab StaffKatie Esterline Ellyn FerriterJon LassondeDenise MaceroniCaroline Gredvig-ArditoMarcy D’Uva
Summer Research Apprentices!Funding SourcesMH45945 NR04279 MH076969MH52415 MH58879NR71120 81ZH-068474 (OGJ)
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Thank you.
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Relevance to Learning, Emotion Regulation and Health
Ron DahlUniversity of California, Berkeley
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Overview• Sleep, Learning, Affect Regulation,
Adolescent Brain Development: A heuristic model– Adolescence as developmental window of
opportunity?
• Consequences of Sleep Loss: – Health relevant spirals of negative effects
• Pragmatics: Clinical, education, and social policy
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continuity and patterning(amount/structure)
arousal
emotion
flexibility, skills, regulation
type(REM/NREM)
A F F E C TA F F E C T
Sleep, Learning, Affect Regulation, & Brain Development
motivation
depth/disruption(initiate/maintain)
circadian(timing/variability)
S L E E PS L E E P
Cognitive Processes, Learning & Brain Plasticity
Developmental TrajectoryBrain/Behavior/Social ContextINTERACTIONS
Clinical and Policy: Early Intervention and Prevention
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Public Health Perspective: The Health Paradox of Adolescence
Adolescence is (physically) the healthiest period of the lifespan: Prior to adult declines; beyond the frailties of infancy and childhood:Improvements in strength, speed, reaction
time, reasoning abilities, immune function …Increased resistance to cold, heat, hunger,
dehydration, and most types of injury …Yet: Overall morbidity and mortality rates
increase 200% from childhood to late adolescence
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Morbidity & Mortality in Adolescence • Primary sources of death/disability are related to
problems with control of behavior and emotion• Increasing rates of accidents, suicide, homicide,
depression, alcohol & substance use, violence, reckless behaviors, eating disorders, STDs, health problems related to risky sexual behaviors… obesity
• Behaviors with long-term health (lifetime) consequences
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Adolescence: an inflection-point in life course trajectory
0
0.02
0.04
0.06
0.08
0.1
0.12
0 10 20 30 40 50 60 70
Age
female
male
Probability of Smoking Initiation
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Alcohol Use by Age
Source: SAMHSA National Survey on Drug Use and Health 2003
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Why the Health Paradox of Adolescence?
• Why is the physically healthiest time of the Why is the physically healthiest time of the life span a period of such high morbidity and life span a period of such high morbidity and mortality? mortality?
• Role of intensifying Role of intensifying affective (emotional and (emotional and motivational) influences on behavior and motivational) influences on behavior and how these how these interactinteract with risk (and risk-with risk (and risk-promoting) promoting) social contextssocial contexts… …
• Role of socio-affective changes at pubertyRole of socio-affective changes at puberty
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Puberty as a Bio-behavioral Activation of Socio-affective Changes
• A natural inclination toward novelty and A natural inclination toward novelty and exploration (Cross species data & evolutionary exploration (Cross species data & evolutionary perspective)perspective)(Individual differences & social context effects)(Individual differences & social context effects)
• Risk taking, sensation-seeking, and erratic (emotionally-influenced) behavior
• Increased motivational salience of social status • Effects of specific hormones? Testosterone?
Estradiol? Oxytocin? (& interactions with dopamine, learning, specific experiences?)
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Human Puberty: Igniting Passions in the Developing Brain
Profound changes in romantic interest, motivation, emotional intensity
Intensification of many types of goal-directed behavior, including intense motivation for long-term and abstract goals (particularly those related to social-status)
Empirical evidence for neurobehavioral changes in emotion and motivation…o A period of natural motivational learning?o A key time for early-intervention:
Emotional disorders, substance use, risk, education…
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Overview of a Tipping Point Model: Overview of a Tipping Point Model: A Maturational Gap? A Maturational Gap?
Onset of puberty: Activational effects primarily on affective neural systems Versus gradual emergence of cognitive controlVersus gradual emergence of cognitive control
[‘starting the emotional/motivational engines [‘starting the emotional/motivational engines without a skilled driver in the seat of cognitive without a skilled driver in the seat of cognitive control’]control’]
Relevance: Earlier timing of pubertyScaffolding/social supportClinical, Educational, and Public Health
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Sleep: Sleep: Pubertal Changes in Pubertal Changes in Sleep Regulation? Sleep Regulation?
• Some developmental changes in sleep regulation appear to be linked to puberty :– Increased sleepiness – Some SWS and REM changes– Circadian/sleep changes
• Consider these biological changes in sleep tendencies, in earlier periods of human history…
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Social factors in contemporary society contribute to
LATE bedtimes/sleep onset times:
• Peers and social activities • Greater freedom to self-select bedtimes • Access to light and stimulating activities • Stress/anxiety or excitement difficulty falling
asleep• Major circadian shift on weekends/vacation• Work, Sports, Homework, Projects, Meds...
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The School-Sleep SqueezeThe School-Sleep Squeeze• Despite Despite averageaverage school night bedtimes of 11:30 school night bedtimes of 11:30
pm in high school seniors, the average wake-up pm in high school seniors, the average wake-up time on school days is 6:15 am. time on school days is 6:15 am.
• Greater than 10% of US high school students Greater than 10% of US high school students must get up before 5:30 am to catch busesmust get up before 5:30 am to catch buses
• More than 15 % of high school students report More than 15 % of high school students report averaging 6 or less hours in bed on school days averaging 6 or less hours in bed on school days (need 8 or more)(need 8 or more)
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Contributing Factors/Vicious Cycle
• “Catch-up” sleep on week-ends pushes circadian system to further delay
• Use of stimulants (caffeine and nicotine) can contribute to Difficulty Falling Asleep
• Stress and conflict contribute to emotional arousal and further Difficulty Falling Asleep
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What are the consequences?
• If 30-40% of U.S. adolescents are typically getting less than optimal sleep, what are the costs?
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Consequences of Insufficient Sleep in Adolescents
• Sleepiness (lapses)Sleepiness (lapses)• Tiredness, motivationTiredness, motivation• Difficulties with focused attentionDifficulties with focused attention• Irritability, reactive aggressionIrritability, reactive aggression• Decreased mood, Decreased mood, depression?depression?• Negative synergy with alcohol effects Negative synergy with alcohol effects • Direct effects on learning, memory consolidationDirect effects on learning, memory consolidation• Increase use of caffeine, stimulantsIncrease use of caffeine, stimulants• Risk for obesity, metabolic syndromeRisk for obesity, metabolic syndrome• Affect regulation?Affect regulation?
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continuity and patterning(amount/structure)
arousal
emotion
flexibility, skills, regulation
type(REM/NREM)
A F F E C TA F F E C T
Sleep, Learning, Affect Regulation, & Brain Development
motivation
depth/disruption(initiate/maintain)
circadian(timing/variability)
S L E E PS L E E P
Cognitive Processes, Learning & Brain Plasticity
Developmental TrajectoryBrain/Behavior/Social ContextINTERACTIONS
Sleep as a victim to the spiral of changes; Sleep deprivation as a contributor to the spiral
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Youth are heavily over-represented in late-night accidents
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Sleep and Irritability/Aggression in Youth
• The relationship between sleeping problems and aggression, anger, and impulsivity in a population of juvenile and young offenders. Ireland JL, Culpin V J. Adolescent Health (2007)
• Sleep and aggression in substance abusing adolescents: results from an integrative, behavioral sleep treatment pilot program. Haynes PL, Bootzin RR, et al. Sleep (2007)
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Evidence for Neural Changes in Emotion and Its Regulation
• Walker lab studies (Yoo et al 2007; Gujar et al 2011)
• Franzen et al 2009
• Increased emotional reactivity and/or diminished cognitive control …?
• Adolescents with sleep deprivation?
• Several studies in progress…
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Example: Sleep & Anxiety in Early Adolescence
• Children with anxiety disorders enter adolescence with several additional vulnerabilities that can amplify both the causes and consequences of sleep problems: – increased vigilance– heightened physiological arousal– a predilection toward bedtime worries and ruminations – sensitivity to social rejection
• Anxiety as a risk factor for depression• Sleep deprivation as risk factor for depression • Depression rates soar during adolescence
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SLEEPING TIGERS
• Thoughts, feelings, and behaviors at bedtime
• Individual motivation (Personal benefits of sleep)
• Good habits (day and night)
• Establishing a regular schedule
• Restricting media use at night (TV, internet, iPod, etc.)
• Savoring and Switching
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Insufficient Sleep in the Adolescent
• Framing the Importance & Value of Sleep– Examining the negative consequences
• School, attention, mood, social, appearance• Risk for tragic outcomes
– Emphasizing the positive• Feeling better, looking better, working toward goals
• Targeting the Enemies to Good Sleep– Late night activities, caffeine, WEEK-ENDS
AND HOLIDAY SCHEDULES
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A Small Set of Biological Changes at Puberty Can Lead to a Spiral of Negative Effects
• Late night/erratic schedules Sleep Deprivation
erodes mood and motivation
greater stress and affective problems
interferes further w sleep/arousal regulation
greater difficulty falling asleep
• Social context that amplifies the biologic change a torrential spiral?
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Targeting the Adolescent Transition:A Period of Multiple Inflection Points/Vulnerabilities
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Thank you
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