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Biological Systems Influenced by Psychological Stress: Sleep

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Title: Biological Systems Influenced by Psychological Stress: Sleep


1
Biological Systems Influenced by Psychological
Stress Sleep
  • Martica Hall, Ph.D.
  • For the PMBC-II Sleep Assessment Resources Core
  • Pittsburgh Mind-Body Center Summer Institute
  • Pittsburgh, PA
  • June 5, 2008

2
Outline for todays presentation
  • What is it?
  • How is it measured?
  • What affects it?
  • Is sleep related to psychological stress?
  • Classic Studies
  • Research Program on Heart Rate Variability During
    Sleep
  • EXTRA MATERIAL Is sleep related to health?
  • Where do we go from here?

3
Overview Description of sleep
  • What is sleep?
  • behavioral state of relative quiescence
  • reversible changes in consciousness and
    physiology
  • seen in all mammals
  • essential to health and functioning
  • What drives sleep?
  • prior wakefulness
  • circadian rhythms
  • Habit
  • Circumstance

4
Overview Functions of sleep
  • Ecological/ environmental advantage
  • Improves the quality of wakefulness
  • Alertness
  • Mood
  • Cognitive (especially frontal lobe) functions
  • Integration of experience learning
  • Resensitization of receptors (e.g.,
    norepinephrine, serotonin)
  • Metabolic, inflammatory effects
  • Longevity

5
Assessment of sleep-wake states
  • Self-report questionnaires
  • Sleep-wake diaries Daily recording of sleep
    times and characteristics
  • Observer ratings Unreliable
  • Actigraphy Motion-sensitive accelerometer worn
    on wrist
  • Polysomnography (PSG) Modification of
    electroencephalography (EEG)
  • EEG
  • Eye movements
  • Muscle tone

6
Actigraphy
Daytime activity peaks
Nighttime inactivity
Actigraph taken off
7
Polysomnography Relaxed wakefulness (Stage w)
8
PSG Stage 1 sleep
9
PSG Stage 2 sleep
10
PSG Stage 3 sleep
11
PSG Stage 4 sleep
12
PSG Rapid-eye-movement (REM) sleep
13
Factors that affect sleep
  • Age
  • Increased wakefulness during sleep period
  • Decreased Stage 3/4 NREM
  • Earlier timing
  • Greater daytime sleepiness
  • Sex (women have longer sleep, more Stage 3/4
    NREM)
  • Timing Sleep is best at night!
  • Illnesses, medications

14
Sleep in healthy young and older adults
15
Sleep stages across the life spanOhayon et al.,
SLEEP 2004 27 1255-73
Minutes
Age (years)
16
Core body temperature
Cortisol
Be mindful of circadian rhythms!Examples of
humancircadian rhythmsCzeisler and Khalsa, 2000
Urine volume
Thyroid Stimulating Hormone
Growth Hormone
Prolactin
Parathyroid Hormone
Motor activity
Time
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Family Conflict in Childhood and Later Insomnia
Gregory et al., SLEEP, 2006N 1037, 52 male
19
Dose-Response Relationship Between Chronicity of
Family Conflict and Later Insomnia Gregory et
al., SLEEP, 2006
Number of assessments at which family scores in
top quartile for family conflict
20
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 lt .01)
21
Perceived Discrimination as a Mediator of the
Race-Sleep Relationship Thomas et al., Health
Psychology (2006)
37 African Americans (mean age 36.08 1.36)
percent Stage 4 1.34 0.44 56 Caucasian
Americans (mean age 35.57 0.96) percent Stage 4
3.89 0.51
22
Prospective assessment of stress, coping, arousal
and sleep Morin, Rodrigue Ivers, Psychosomatic
Medicine (2003)
Mid-life patients w/ insomnia and good sleeper
controls, n64) Data self-report daily diaries
collected over 3 weeks. Stressors were naturally
occurring events.
23
Research Program on Heart Rate Variability During
SleepHow is it evaluated? Why is it
important?Is it related to stress?
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Heart Rate Variability Why is it important?
Heart Rate Variability
Proximal Indices of Health
Health Outcomes
27
Heart Rate Variability Health Its not just a
waking phenomenon
Heart Rate Variability
Proximal Indices of Health
Health Outcomes
HRV during Sleep
28
Why am I interested in HRV during sleep?
  • Fundamental belief Sleep is an essential
    restorative behavior that affects and can be
    affected by stress and other negative affective
    states. These relationships are critical to
    health and functioning.
  • Research program Focuses on characterizing the
    bi-directional relationship between stress and
    sleep and its impact on health and functioning.
  • Why HRV during sleep? Evaluation of HRV during
    sleep provides non-invasive, continuous measure
    of autonomic nervous system regulation during
    sleep.
  • QEKG techniques allow us to parse signal into
    vagal and sympathovagal components.
  • These data allow us to test and refine hypotheses
    about the pathways linking stress, sleep and
    health.

29
Initial foray into evaluating HRV during sleep
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.
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Assessment of HRV during sleepusing MindWare
SleepSCORE SWAN Sleep StudyNeurobiology of
Insomnia Sleep in Renal DiseaseTreatment of
Sleep Disorders in PTSD Sleep Apnea and the
Metabolic SyndromeDepression in CHF
Patients Sleep Deprivation and StressSleep and
HRV in Premature Infants Brain Metabolism during
Sleep
37
Study Sample
  • Participants were recruited from the Heart
    Strategies Concentrating on Risk Evaluation
    (HeartSCORE) community study of population
    disparities in cardiovascular risk.
  • HeartSCORE eligibility criteria were age 45
    75 years, resident of the greater Pittsburgh
    metropolitan area and absence of comorbid
    conditions expected to limit life expectancy to lt
    5 years.
  • The SleepSCORE study included a sub-sample of
    HeartSCORE participants, stratified by gender,
    race and Framingham Risk.
  • SleepSCORE exclusion criteria were pregnancy,
    current treatment of sleep apnea, regular use of
    sleep medications, nighttime shift work,
    medication for diabetes, or prior diagnosis of
    CVD events or interventional cardiology
    procedures.

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Participant Characteristics
Percent Mean (s.d.) Males 54 Af
rican American 42 BMI 29.6
(4.9) Income (below 40,000) 46 Education (no
college degree) 50 Smoke (current)
7 Perceived Stress (PSS) 4.1 (2.6) Symptoms
of Depression (CES-D) 7.5 (7.6) Symptoms of
Anxiety (STAI) 6.3 (5.4) Hostility
(CM-Ho) 1.5 (1.4)
40
Sleep Characteristics
Mean (s.d.) Sleep Quality (PSQI)
6.3 (3.1) Time Spent Asleep (mins.) 361.0
(66.9) Sleep Efficiency (percent) 77.0
(11.1) NREM Stage 1 (percent) 9.2 (5.9) NREM
Stage 2 (percent) 61.4 (9.2) NREM Stage 34
(percent) 6.5 (7.3) REM Sleep (percent)
22.8 (6.0) AHI 4.6 (17.5)
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NREM differs from Wakefulness REM
HF Power LFHF
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Brachial artery diameter is a significant
correlate of LFHF HRV during NREM sleep
r 0.25, p lt .01
49
Brachial artery diameter is a significant
correlate of LFHF HRV throughout NREM sleep
BAD gt 3.7
BAD lt 3.7
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Extra Material Mind-Body Sleep Research Bridging
the Gap Between Behavioral Medicine and Sleep
Medicine
SLEEP
HEALTH
Sleep Restriction/Deprivation Sleep
Duration Sleep Continuity Sleep
Architecture Sleep/Wake Rhythms Sleep Disorders
54
Sleep Restriction Sleepiness Performance (n
16, sleep restriction to 33 below habitual sleep
duration)
Dinges et al., SLEEP. 20267-77 (1997).
55
Sleep deprivation effects on cognitive function
Drummond et al., Neuroreport, 1999
Normal sleep Activation of PFC, parietal,
pre-motor cortex
Following sleep deprivation Decreased activation
fMRI during serial subtraction task
56
Sleep Restriction Glucose Metabolism
Glucose Effectiveness 30 40 decrease Sympathov
agal Balance (trend) increase Spiegel et al.,
Lancet, 3541435-9 (1999). Ghrelin Leptin 70
increase Carbohydrate Craving 30
Increase Spiegel et al., Ann Intern. Med,
141846-50 (2004).
GLUCOSE (mg/dL) LEPTIN (ng/ml)
57
Sleep Duration and Health
Sleep Duration and Mortality -- one
example Kripke et al., 2003, Arch Gen
Psychiatry, 59131-136. Sleep Duration and
Cardiovascular Disease (CVD) Ayas et al., Arch
Intern Med, 163205-209, 2003. Heslop et al.,
Sleep Medicine, 3305-314, 2002. Qureshi et al.,
Neurology, 48904-11, 1997. lt5 6 7 8 gt9
RR RR RR RR Total CHD 1.39 1.18 1.10 -- 1.38
Nonfatal MI 1.52 1.32 1.23 -- 1.35 Fatal
CHD 1.12 0.91 0.83 -- 1.45
58
Markers of Inflammation Attenuate the
Relationship Between Short Sleep and Mortality
The Health ABC Study of Older Adults
3.0 2.75 2.5 2.25 2.0 1.75 1.5 1.25 1.0 0.75 0.5
Crude Adjusted 1 Adjusted 2
Mortality Hazards Ratio




lt 6
6 7 8 gt8
Sleep Duration, Compared to Reference of 7 Hours
Hall, Newman et al. (under review)
59
Sleep Continuity Survival as a Function of
PSG-Assessed Sleep Latency Dew et al.,
Psychosomatic Medicine (2003)
1.0 0.8 0.6 0.4 0.2 0.0
Log rank test 9.63 p .002
Cumulative Survival
Latency, lt 30 min.
Latency, gt 30 min.
0 100 200 300 400 500 600
700 800 900 1000Weeks
60
Sleep Duration the Metabolic SyndromeHall et
al., SLEEP (2008)
Aim To evaluate the relationship between
reported habitual sleep duration and the
metabolic syndrome in a community sample of
healthy men and women. Hypothesis Short sleep
duration is associated with an increased risk of
having the metabolic syndrome after adjusting for
age, sex, race, and symptoms of
depression. Study Adult Human Behavior
Project (AHAB HL-04962) Exclusions clinical
history of atherosclerotic disease cancer
diagnosis or treatment w/in the past year
chronic liver or kidney disease use of insulin,
weight loss or psychotropic medications.
61
Reported Habitual Sleep Duration (hrs/night)
600 500 400 300 200 100 0
number
lt 6 6 to lt 7 7 to 8 gt8 to lt 9
gt 9
62
Metabolic Syndrome and its NCEP-Defined Components
lt 6 6 to lt7 7 to 8 gt8 n
187 n 402 n 525 n
100
Metabolic Syndrome 1.59 1.34 ref
1.69 (1.1 2.4) (.99 1.9)
(1.00 2.9) Abdominal Obesity 1.55
1.48 ref 1.51 (1.1 2.2)
(1.1 2.0) (.96 2.4) Glucose
1.62 1.13 ref 1.68 (1.1
2.4) (.83 1.5) (1.04 2.7) Blood
Pressure 1.07 .94 ref
.98 (.73 1.6) (.70 1.3)
(.6 1.6) Triglycerides 1.21 1.42
ref .92 (.80 1.8)
(1.03 2.0) (.51 1.7) High Density
1.24 1.15 ref 1.52
Lipoproteins (.86 1.8) (.85 1.5)
(.98 2.4)
63
SWAN Sleep Study Protocol
Hall et al. (under preparation)
DAILY Fill out Sleep Diary and Wear Wrist
Actigraph (LENGTH OF STUDY 1 menstrual cycle or
35 days)
PSG Sleep Study (3 nights)
DAY 1 DAY 4
DAY 14
FINAL STUDY DAY
Core SWAN Visit w/in 6 months pre- or post-sleep
study Metabolic Syndrome determination by clinic
blood pressure blood draw waist measurement
height weight.
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Shiftwork and Ulcers Drake et al., SLEEP (2004)
N 2,570 18 65 52 Male
2036 174 360
68
Insomnia Epidemiology Ohayon, Sleep Med Rev,
2002
Direct economic costs of insomnia in the US are
estimated 14 billion
69
Insomnia Is a Risk Factorfor Psychiatric
Disorders
18
Insomnia (n 240)
No Insomnia (n 739)
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14
12
10
Incidence () MoreThan 3.5 Years
8
6
4
2
0
Depression
Anxiety
Alcohol
Drug
95 CI for odds ratio excludes 1.0. Breslau N et
al. Biol Psychiatry. 199639411-418.
70
Association of insomnia and CHD events Schwartz,
J Psychosom Res, 1999 47313-33
Combined estimate
Individual studies
Meta-analysis of seven cohort and longitudinal
studies
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Sleep disorders are under-diagnosed
  • As many as 95 of people with a sleep problem
    remain unidentified and undiagnosed
  • Few health care providers question patients about
    sleep
  • Little content in medical schools
  • Essentially everything learned about sleep is in
    post-graduate courses (a booming academic
    business)

76
Sleep Disorders are Costly
  • Possibly 100,000 motor vehicle accidents annually
    are sleep-related.
  • The annual direct cost estimate of sleep-related
    problems is 16 billion, with an additional
    50-100 billion in indirect costs
  • Accidents
  • Litigation
  • Property destruction
  • Hospitalization
  • Death

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Sleep disorders medicine and mind-body
interactions
  • Sleep medicine is in its adolescence as a field
  • Understanding mind-body interactions with respect
    to sleep is in its infancy
  • Fundamental processes relating sleep as a
    mediator of M-B processes is very much needed
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