Biological Systems Influenced by Biological Systems Influenced by Psychological Stress: Sleep Psychological Stress: Sleep Martica Hall, Ph.D. Martica Hall, Ph.D. For the PMBC-II Sleep Assessment & For the PMBC-II Sleep Assessment & Resources Core Resources Core Pittsburgh Mind-Body Center Summer Institute Pittsburgh Mind-Body Center Summer Institute Pittsburgh, PA Pittsburgh, PA June 5, 2008 June 5, 2008
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Biological Systems Influenced by Psychological Stress: Sleep Martica Hall, Ph.D. For the PMBC-II Sleep Assessment & Resources Core Pittsburgh Mind-Body.
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Biological Systems Influenced by Biological Systems Influenced by Psychological Stress: SleepPsychological Stress: Sleep
Martica Hall, Ph.D.Martica Hall, Ph.D.For the PMBC-II Sleep Assessment & Resources CoreFor the PMBC-II Sleep Assessment & Resources CorePittsburgh Mind-Body Center Summer InstitutePittsburgh Mind-Body Center Summer Institute
Pittsburgh, PAPittsburgh, PA
June 5, 2008June 5, 2008
Outline for today’s Outline for today’s presentationpresentation
What is it? What is it?
How is it measured? How is it measured?
What affects it?What affects it?
Is sleep related to psychological stress?Is sleep related to psychological stress?– Classic StudiesClassic Studies– Research Program on Heart Rate Variability During SleepResearch Program on Heart Rate Variability During Sleep
EXTRA MATERIAL: Is sleep related to health?EXTRA MATERIAL: Is sleep related to health?
Where do we go from here?Where do we go from here?
Overview: Description of sleepOverview: Description of sleep
What is sleep?What is sleep? behavioral state of relative quiescencebehavioral state of relative quiescence reversible changes in consciousness and physiologyreversible changes in consciousness and physiology seen in all mammals seen in all mammals essential to health and functioningessential to health and functioning
What drives sleep? What drives sleep? prior wakefulnessprior wakefulness circadian rhythmscircadian rhythms Habit Habit CircumstanceCircumstance
Overview: Functions of sleepOverview: Functions of sleep
Ecological/ environmental advantageEcological/ environmental advantage Improves the quality of wakefulnessImproves the quality of wakefulness
– AlertnessAlertness
– MoodMood
– Cognitive (especially frontal lobe) functionsCognitive (especially frontal lobe) functions Integration of experience; learningIntegration of experience; learning Resensitization of receptors (e.g., norepinephrine, Resensitization of receptors (e.g., norepinephrine,
Assessment of sleep-wake statesAssessment of sleep-wake states
Self-report questionnairesSelf-report questionnaires Sleep-wake diariesSleep-wake diaries: Daily recording of sleep times and : Daily recording of sleep times and
characteristicscharacteristics Observer ratingsObserver ratings: Unreliable: Unreliable ActigraphyActigraphy: Motion-sensitive accelerometer worn on : Motion-sensitive accelerometer worn on
wristwrist PolysomnographyPolysomnography (PSG): Modification of (PSG): Modification of
– Greater daytime sleepinessGreater daytime sleepiness Sex (women have longer sleep, more Stage 3/4 Sex (women have longer sleep, more Stage 3/4
NREM)NREM) Timing: Sleep is best at night!Timing: Sleep is best at night! Illnesses, medicationsIllnesses, medications
Sleep in healthy young and older adultsSleep in healthy young and older adults
20 year old woman 71 year old woman
Sleep stages across the life spanSleep stages across the life spanOhayon et al., SLEEP 2004; 27: 1255-73Ohayon et al., SLEEP 2004; 27: 1255-73
Min
ute
s
Age (years)
Be mindful of Be mindful of circadian circadian rhythms!rhythms!
Examples of Examples of humanhumancircadian circadian rhythmsrhythmsCzeisler and Khalsa, 2000Czeisler and Khalsa, 2000
Core body temperature
Urine volume
Thyroid StimulatingHormone
Growth Hormone
Prolactin
Parathyroid Hormone
Motor activity
Cortisol
Time
Family Conflict in Childhood and Family Conflict in Childhood and Later InsomniaLater Insomnia Gregory et al., Gregory et al., SLEEPSLEEP, 2006, 2006
N = 1037, 52% maleN = 1037, 52% male
Dose-Response Relationship Between Dose-Response Relationship Between Chronicity of Family Conflict and Later Chronicity of Family Conflict and Later Insomnia Insomnia Gregory et al., Gregory et al., SLEEPSLEEP, 2006, 2006
Number of assessments at which family scores in top quartile for family conflictNumber of assessments at which family scores in top quartile for family conflict
Gene by Environment Interactions Reveal Vulnerability to Stress-Related Sleep Disturbances Brummet et al., Psychosomatic Medicine (2007)
Caregivers homozygous for the s allele had greater subjective sleep Complaints compared to all other groups (p < .01)
Perceived Discrimination as a Mediator ofthe Race-Sleep Relationship Thomas et al., Health Psychology (2006)
Indices of HealthIndices of Health Health OutcomesHealth Outcomes
HRV HRV duringduringSleepSleep
Heart Rate Variability & Health: It’s not just a Heart Rate Variability & Health: It’s not just a waking phenomenonwaking phenomenon
Why am I interested in HRV during sleep?Why am I interested in HRV during sleep?
Fundamental beliefFundamental belief: Sleep is an essential restorative behavior that affects and : Sleep is an essential restorative behavior that affects and can be affected by stress and other negative affective states. These can be affected by stress and other negative affective states. These relationships are critical to health and functioning.relationships are critical to health and functioning.
Research programResearch program: Focuses on characterizing the bi-directional relationship : Focuses on characterizing the bi-directional relationship between stress and sleep and its impact on health and functioning.between stress and sleep and its impact on health and functioning.
Why HRV during sleepWhy HRV during sleep? Evaluation of HRV during sleep provides non-invasive, ? Evaluation of HRV during sleep provides non-invasive, continuous measure of autonomic nervous system regulation during sleep. continuous measure of autonomic nervous system regulation during sleep.
QEKG techniques allow us to parse signal into vagal and sympathovagal QEKG techniques allow us to parse signal into vagal and sympathovagal components.components.
These data allow us to test and refine hypotheses about the pathways linking These data allow us to test and refine hypotheses about the pathways linking stress, sleep and health.stress, sleep and health.
Psychological stress and related negative affective states have been associated with prolonged physiological arousal during sleep. Might they elicit changes in heart rate variability during sleep?
We evaluated this hypothesis in two studies using autoregressive spectral analysis of the EKG during NREM and REM sleep.
Study 1: Acute Laboratory stress in 64 healthy undergraduates.
Study 2: Stress-related coping behaviors in patients with insomnia.
Whether these relationships generalize to older adults and across racial/ethnic groups is not known.
Initial foray into evaluating HRV during sleepInitial foray into evaluating HRV during sleep
SleepSCORE SleepSCORE SWAN Sleep StudySWAN Sleep StudyNeurobiology of InsomniaNeurobiology of Insomnia Sleep in Renal DiseaseSleep in Renal DiseaseTreatment of Sleep Disorders in PTSDTreatment of Sleep Disorders in PTSD Sleep Apnea and the Metabolic SyndromeSleep Apnea and the Metabolic SyndromeDepression in CHF PatientsDepression in CHF Patients Sleep Deprivation and StressSleep Deprivation and StressSleep and HRV in Premature InfantsSleep and HRV in Premature Infants Brain Metabolism during SleepBrain Metabolism during Sleep
Assessment of HRV during sleepAssessment of HRV during sleepusing MindWareusing MindWare
Study SampleStudy Sample
Participants were recruited from the Heart Strategies Concentrating Participants were recruited from the Heart Strategies Concentrating on Risk Evaluation (HeartSCORE) community study of population on Risk Evaluation (HeartSCORE) community study of population disparities in cardiovascular risk. disparities in cardiovascular risk.
HeartSCORE eligibility criteria were: age 45 – 75 years, resident of HeartSCORE eligibility criteria were: age 45 – 75 years, resident of the greater Pittsburgh metropolitan area and absence of comorbid the greater Pittsburgh metropolitan area and absence of comorbid conditions expected to limit life expectancy to < 5 years. conditions expected to limit life expectancy to < 5 years.
The SleepSCORE study included a sub-sample of HeartSCORE The SleepSCORE study included a sub-sample of HeartSCORE participants, stratified by gender, race and Framingham Risk.participants, stratified by gender, race and Framingham Risk.
SleepSCORE exclusion criteria were pregnancy, current treatment SleepSCORE exclusion criteria were pregnancy, current treatment of sleep apnea, regular use of sleep medications, nighttime shift of sleep apnea, regular use of sleep medications, nighttime shift work, medication for diabetes, or prior diagnosis of CVD events or work, medication for diabetes, or prior diagnosis of CVD events or interventional cardiology procedures. interventional cardiology procedures.
REM Sleep (percent)REM Sleep (percent) 22.8 (6.0) 22.8 (6.0)
AHIAHI 4.6 (17.5) 4.6 (17.5)
NREM differs from Wakefulness & REMNREM differs from Wakefulness & REM
HF PowerHF Power LF:HFLF:HF
Brachial artery diameter is a significant correlate Brachial artery diameter is a significant correlate of LF:HF HRV during NREM sleepof LF:HF HRV during NREM sleep
r = 0.25, p < .01r = 0.25, p < .01
NREM Period
1 2 3 4
Lo
g(L
F:H
F)
0.4
0.6
0.8
1.0
1.2
1.4
NREM Period
1 2 3 4
Lo
g(L
F:H
F)
0.4
0.6
0.8
1.0
1.2
1.4
Brachial artery diameter is a significant correlate Brachial artery diameter is a significant correlate of LF:HF HRV throughout NREM sleepof LF:HF HRV throughout NREM sleep
Extra MaterialExtra MaterialMind-Body Sleep Research: Bridging the Gap Mind-Body Sleep Research: Bridging the Gap Between Behavioral Medicine and Sleep MedicineBetween Behavioral Medicine and Sleep Medicine
Sleep deprivation effects on cognitive Sleep deprivation effects on cognitive function function Drummond et al., Drummond et al., NeuroreportNeuroreport, 1999, 1999
Normal sleep – Activation of PFC, parietal, pre-motor cortex
Following sleep deprivation – Decreased activation
Spiegel et al., Spiegel et al., Ann Ann Intern. MedIntern. Med, 141:846-, 141:846-50 (2004).50 (2004).
GLUCOSGLUCOSEE(mg/dL)(mg/dL)
LEPTINLEPTIN(ng/ml)(ng/ml)
Sleep Duration and Mortality -- one example:Sleep Duration and Mortality -- one example:Kripke et al., 2003, Kripke et al., 2003, Arch Gen PsychiatryArch Gen Psychiatry, 59:131-136., 59:131-136.
Sleep Duration and Cardiovascular Disease Sleep Duration and Cardiovascular Disease (CVD)(CVD)Ayas et al., Ayas et al., Arch Intern MedArch Intern Med, 163:205-209, 2003., 163:205-209, 2003.Heslop et al., Heslop et al., Sleep MedicineSleep Medicine, 3:305-314, 2002., 3:305-314, 2002.Qureshi et al., Qureshi et al., NeurologyNeurology, 48:904-11, 1997., 48:904-11, 1997.
Sleep Duration, Compared to Reference of 7 HoursSleep Duration, Compared to Reference of 7 Hours
CrudeAdjusted 1Adjusted 2
Markers of Inflammation Attenuate the Markers of Inflammation Attenuate the Relationship Between Short Sleep and Relationship Between Short Sleep and Mortality: The Health ABC Study of Older AdultsMortality: The Health ABC Study of Older Adults
Markers of Inflammation Attenuate the Markers of Inflammation Attenuate the Relationship Between Short Sleep and Relationship Between Short Sleep and Mortality: The Health ABC Study of Older AdultsMortality: The Health ABC Study of Older Adults
Hall, Newman et al. (under review)Hall, Newman et al. (under review)
Sleep Continuity: Survival as a Function of PSG-Assessed Sleep LatencyDew et al., Psychosomatic Medicine (2003)
Latency, < 30 min.
Latency, > 30 min.
0 100 200 300 400 500 600 700 800 900 1000
Weeks
1.0
0.8
0.6
0.4
0.2
0.0
Cum
ulat
ive
Sur
viva
l
Log rank test = 9.63
p = .002
Sleep Duration & the Metabolic SyndromeSleep Duration & the Metabolic SyndromeHall et al., SLEEP (2008)Hall et al., SLEEP (2008)
Sleep Duration & the Metabolic SyndromeSleep Duration & the Metabolic SyndromeHall et al., SLEEP (2008)Hall et al., SLEEP (2008)
AimAim To evaluate the relationship between reported To evaluate the relationship between reported habitual sleep duration and the metabolic syndrome in a habitual sleep duration and the metabolic syndrome in a community sample of healthy men and women.community sample of healthy men and women.
HypothesisHypothesisShort sleep duration is associated with an increased risk Short sleep duration is associated with an increased risk of having the metabolic syndrome after adjusting for of having the metabolic syndrome after adjusting for age, sex, race, and symptoms of depression.age, sex, race, and symptoms of depression.
StudyStudy: Adult & Human Behavior Project (AHAB; HL-: Adult & Human Behavior Project (AHAB; HL-04962)04962)Exclusions: clinical history of atherosclerotic disease; Exclusions: clinical history of atherosclerotic disease; cancer diagnosis or treatment w/in the past year; cancer diagnosis or treatment w/in the past year; chronic liver or kidney disease; use of insulin, weight chronic liver or kidney disease; use of insulin, weight loss or psychotropic medications.loss or psychotropic medications.
< 6 6 to < 7 7 to 8 >8 to < 9 < 6 6 to < 7 7 to 8 >8 to < 9 >> 9 9
nu
mb
er
nu
mb
er
Metabolic Syndrome and its NCEP-Defined Metabolic Syndrome and its NCEP-Defined ComponentsComponentsMetabolic Syndrome and its NCEP-Defined Metabolic Syndrome and its NCEP-Defined ComponentsComponents
< 6 6 to <7 7 to 8 >8< 6 6 to <7 7 to 8 >8n = 187n = 187 n = 402 n = 525 n = 100 n = 402 n = 525 n = 100
DAILY: Fill out Sleep Diary and Wear Wrist ActigraphDAILY: Fill out Sleep Diary and Wear Wrist Actigraph(LENGTH OF STUDY: 1 menstrual cycle or 35 days)(LENGTH OF STUDY: 1 menstrual cycle or 35 days)
DAY 14DAY 14 FINAL FINAL STUDY STUDY
DAYDAY
PSG Sleep PSG Sleep Study Study
(3 nights)(3 nights)
SWAN Sleep Study: ProtocolSWAN Sleep Study: Protocol Hall et al. (under preparation)Hall et al. (under preparation)
SWAN Sleep Study: ProtocolSWAN Sleep Study: Protocol Hall et al. (under preparation)Hall et al. (under preparation)
Core SWAN Visit w/in 6 months pre- or post-sleep study:Core SWAN Visit w/in 6 months pre- or post-sleep study:Metabolic Syndrome determination by clinic blood pressure; Metabolic Syndrome determination by clinic blood pressure;
Shiftwork and Ulcers Shiftwork and Ulcers Drake et al., Drake et al., SLEEP (SLEEP (2004)2004)
20362036 174 174 360 360
N = 2,570N = 2,57018 – 6518 – 6552% Male52% Male
Insomnia Epidemiology Insomnia Epidemiology Ohayon, Ohayon, Sleep Med RevSleep Med Rev, 2002, 2002
Insomnia symptoms + daytime consequences
9-15%
Insomnia symptoms-Overall prevalence 30-48%-Often or always: 16-21%-Moderate to extreme: 10-28%
Insomnia diagnosis
6%Direct economic costsDirect economic costsof insomnia in the US of insomnia in the US are estimated ~ $14 billionare estimated ~ $14 billion
Insomnia Is a Risk FactorInsomnia Is a Risk Factorfor Psychiatric Disordersfor Psychiatric Disorders
0
2
4
6
8
10
12
14
16
18
Depression* Anxiety* Alcohol Drug*
Inci
denc
e (%
) M
ore
Tha
n 3.
5 Y
ears
Insomnia (n = 240) No Insomnia (n = 739)
*95% CI for odds ratio excludes 1.0.Breslau N et al. Biol Psychiatry. 1996;39:411-418.
0
1
2
3
Relative Risk
Association of insomnia and CHD Association of insomnia and CHD events events Schwartz, Schwartz, J Psychosom ResJ Psychosom Res, 1999; 47:313-33, 1999; 47:313-33
Combined estimate
Individual studies
Meta-analysis of seven cohort and longitudinal studies
Sleep disorders are under-diagnosedSleep disorders are under-diagnosed
As many as 95% of people with a sleep problem remain As many as 95% of people with a sleep problem remain unidentified and undiagnosed unidentified and undiagnosed
Few health care providers question patients about sleepFew health care providers question patients about sleep
Little content in medical schoolsLittle content in medical schools
Essentially everything learned about sleep is in post-Essentially everything learned about sleep is in post-graduate courses (a booming academic business) graduate courses (a booming academic business)
Sleep Disorders are CostlySleep Disorders are Costly
Possibly 100,000 motor vehicle accidents annually Possibly 100,000 motor vehicle accidents annually are sleep-related.are sleep-related.
The annual direct cost estimate of sleep-related The annual direct cost estimate of sleep-related problems is problems is $16 billion$16 billion, with an additional , with an additional $50-$100 $50-$100 billionbillion in indirect costs: in indirect costs:– AccidentsAccidents– LitigationLitigation– Property destruction Property destruction – Hospitalization Hospitalization – DeathDeath
Sleep disorders medicine and mind-body Sleep disorders medicine and mind-body interactionsinteractions
Sleep medicine is in its adolescence as a fieldSleep medicine is in its adolescence as a field
Understanding mind-body interactions with respect to sleep is in Understanding mind-body interactions with respect to sleep is in its infancyits infancy
Fundamental processes relating sleep as a mediator of M-B Fundamental processes relating sleep as a mediator of M-B processes is very much neededprocesses is very much needed