Science Talk-091012-楊健銘
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Transcript of Science Talk-091012-楊健銘
S L E E PS L E E P
國立政治大學 心理學系
S L E E PS L E E P
國立政治大學 心理學系
由基礎研究到臨床應用 ─談失眠的病理機制
政治大學心理學系楊建銘
睡SLEEP
Outline
Neurophysiological Mechanisms of
Sleep/Wake Regulation
Neurobehavioral Model of Insomnia
Clinical Implications
睡SLEEP NEUROPHYSIOLOGICAL MECHNISMS
OF SLEEP/WAKE REGULATION
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Brain Systems for Sleep/Wake Regulation
“Sleep is of the brain, by the brain and for the brain.”
~ Allan Hobson, 2005, Nature
睡SLEEPNeurophysiological Aspectsof Sleep/Wake Regulation
Sleep
vs.
Wake/Arousal
Homeostatic
System
Circadian
System
Arousal
System
Two-
process
model
of sleep
regulation
睡SLEEP
Neurophysiological Aspectsof Sleep/Wake Regulation
Sleep
vs.
Wake/Arousal
Homeostatic
System
Circadian
System
Arousal
System
睡SLEEP
Homeostatic Regulation
of Sleep The homeostatic sleep drive is determined by the
amount of prior sleep and waking/activities.
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睡SLEEP
Neurophysiological Aspectsof Sleep/Wake Regulation
Sleep
vs.
Wake/Arousal
Homeostatic
System
Circadian
System
Arousal
System
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Free Running Study
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Forced
Desynchrony
Protocol
20 hours/”day”
Core body
temperature &
Melatonin rhythms
= 24 hrs 15 mins
(Czeisler, 2000)
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Intrinsic Circadian Period
(Forced desynchrony protocol)
0
1
2
3
4
5
6
7
8
23.8 23.9 24 24.1 24.2 24.3 24.4 24.5 24.6
Intrinsic circadian period (hours)
Num
ber
of
subje
cts
Young (n = 11)
Older (n = 13)
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Circadian Regulation of Sleep
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Light & Circadian Rhythms
Neural pathway
- Melanopsin in ganglion cells of retina
- Retinohypothalamic tract
- SCN
PRC of light on phase shifting
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PRC Curve of Light
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Circadian Regulation of Sleep
Genetic control of circadian process
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Neurophysiological Aspectsof Sleep/Wake Regulation
Sleep
vs.
Wake/Arousal
Homeostatic
System
Circadian
System
Arousal
System
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Arousal System
The arousal system does not regulate sleep directly, but may inhibit sleep by promoting waking and arousal.
Factors that may trigger arousal:
- Sensory stimulus
- Emotion and motivation
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睡SLEEP NEUROBEHAVIORAL MODEL
OF INSOMNIA
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Neurophysiological Aspectsof Sleep/Wake Regulation
Sleep
vs.
Wake/Arousal
Homeostatic
System
Circadian
System
Arousal
System
睡SLEEP
Homeostatic Regulation in Insomnia Neurophysiological findings
- Reduced EEG slow wave activity (Merica & Gaillard, 1992)
- Reduced brain GABA measured by Proton Magnetic Resonance Spectroscopy (Winkelman et al., 2008)
- The increase of slow wave activity after sleep deprivation seen in normal sleepers was less obvious in insomnia patients (Gaillard, 1978; Reynolds et al., 1984; Schneider-Helmert, Whitehouse, Kumar, & Lijzenga, 2001)
Psychological/Behavioral factors- Sleeping outside of the nocturnal sleep period
- Reduced daytime activities
- Increased resting in bed
- Coffee drinking
睡SLEEP
Neurophysiological Aspectsof Sleep/Wake Regulation
Sleep
vs.
Wake/Arousal
Homeostatic
System
Circadian
System
Arousal
System
睡SLEEP
Circadian Regulation in Insomnia Neurophysiological findings
- Shifting in circadian phase: Circadian
Rhythm Sleep Disorders
- Extreme circadian type or less flexible
circadian system as a predisposing factor
- Decreased melatonin level in insomniacs?
Psychological/Behavioral Factors
- Irregular or changes of sleep-wake schedule
- Sleep-in during weekend to catch up lost sleep
- Lack of environmental time cues (e.g. light
exposure)
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A Case of Young Adults Complaining of Insomnia
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SSS SSS
週末晚睡晚起的影響研究
延後實驗情境
週一至
週四
週五
週六
週日 SSS SSS
pm am
*8:00 10:00 12:00 2:00 4:00 6:00 8:00 10:00
* The timing indicated is for subjects whose habitual
bedtime is 11:00 pm and wake-up time is 7:00 am.
VAMS VAMS
Sleep Log
Cognitive Tests
pm am
*8:00 10:00 12:00 2:00 4:00 6:00 8:00 10:00
基準實驗情境
VAMS VAMS
Sleep Log
Cognitive Tests
Wake Sleep
睡SLEEP
SSS ratings on Sunday night
BT = bedtime; * p< .05
0
1
2
3
4
5
6
BT-3h BT-2h BT-1h BT-1/2h* BT*
SS
S R
ati
ng
Time
Baseline Week
Delayed Week
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Sunday Night Sleep Logs
Baseline Delayed
Item Mean SD Mean SD t p
SOL 12.98 15.86 19.69 27.98 1.81 0.083
WASO 1.13 2.03 0.67 1.33 -1.33 0.196
TBT 476.74 37.51 474.41 38.13 -0.66 0.516
TST 465.65 39.39 454.00 44.06 -1.78 0.087
Sleep Quality 5.62 1.17 5.62 1.13 0.00 1.000
Diff. Waking 3.31 1.38 3.35 1.47 0.14 0.890
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Cognitive Tests on Monday Morning
0
5
10
15
20
25
30
Baseline Week
Delayed Week
0
2
4
6
8
10
12
Controlled Oral Word-list
Word Association Memory Test
t = -3.49, p = .002 t = -2.71, p = .011
Number
of
Words
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Monday MorningMood Scales
Baseline Delayed
Item Mean SD Mean SD t p
Monday morning
Alert 48.96 24.74 34.96 18.26 -2.49* 0.019
Sad 14.98 19.42 19.64 18.83 1.01 0.321
Tense 29.07 24.42 34.20 21.99 0.83 0.414
Effort 57.77 24.92 44.61 26.75 1.97 0.059
Happy 44.57 25.50 37.38 18.89 -1.22 0.232
Hungry 38.07 30.60 34.61 26.27 -0.48 0.634
Weary 41.02 31.81 49.36 25.52 1.38 0.180
Irritable 30.70 30.52 45.95 28.95 2.75* 0.010
Sleepy 47.34 29.15 68.00 21.17 3.25** 0.003
Angry 18.61 20.95 30.25 25.97 2.21* 0.036
Sexual 17.80 19.11 16.96 18.80 -0.29 0.775
Overall 59.71 23.60 44.48 18.40 -2.78* 0.010
*p < .05 **p < .005
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Salivary DLMO: After delayed
weekend schedule
19.00
20.00
21.00
22.00
23.00
24.00
Friday Monday
Tim
e
#1
#2
#4
#5
#7
#11
#12
#16
#17
#19
Average
睡SLEEP
Neurophysiological Aspectsof Sleep/Wake Regulation
Sleep
vs.
Wake/Arousal
Homeostatic
System
Circadian
System
Arousal
System
睡SLEEP
Arousal Systemin Insomnia
Physiological hyperarousal, as measured by- CNS activities: e.g. EEG, PET, ……
- ANS indices: e.g. heart rate, HRV, VO2, ……
- Stress related hormones
Psychological/Behavioral Factors- Stress
- Emotional disturbances
- Cognitive hyperarousal
- Conditioning of arousal
- Use of stimulants
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ERPs in the first 5 min S2 sleep
(Yang & Lo, 2007)
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Neurobehavioral Model
of Insomnia
Sleep
vs.
Wake/Arousal
Homeostatic
System
Circadian
System
Arousal
System
Behavioral
Practices
Sleep
Cognition
Emotional
Arousal
Psychological/Behavioral
Facotrs
Neurophysiological
Systems
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Cognitive Model of Insomnia (Harvey, 2002)
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Dysfunctional Sleep Beliefs
in Young Adults (19.7±1.5 years old)
Table 1. Group comparisons between subjects with frequent sleep disturbance (WSD) and without frequent sleep disturbance
(NSD) of the scores on the FIRST and the DBAS-10
WSD group NSD group
Effect
Size*(N = 383) (N = 145)
Mean SD Mean SD F p
FIRST 22.6 4.75 18.88 4.76 64.17 < .001 0.78
DBAS-10
Total Score 60.91 14.4 53.29 15.01 28.76 < .001 0.52
Factor I 32.81 8.78 30.27 9.29 8.55 0.004 0.29
Factor II 16.43 5.17 13.72 5.04 29.35 < .001 0.53
Factor III 11.67 4.08 9.3 4.1 35.29 < .001 0.58
* Cohen's d effect size for the mean difference.
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Dysfunctional Beliefs vs. Vulnerability to
Insomnia in Non-insomniac Young Adults
Table II. Correlations between the FIRST score and the DBAS-10 factor and item scores in the subjects
without frequent sleep disturbance (N = 145)
Factor/Item ContentCorrelation with
the FIRST score
DBAS Factor I Beliefs about the immediate negative consequences of insomnia 0.27**
DBAS Factor IIBeliefs about the long-term negative consequences of insomnia
0.33**
DBAS Factor III Beliefs about the need for control over insomnia 0.35 **
DBAS-10 01 Need 8 hours of sleep to function 0.15**
DBAS-10 02 Need to catch up on poor sleep 0.12**
DBAS-10 03 Insomnia seriously affects health 0.18**
DBAS-10 04Should stay in bed and try harder when having sleep problems
0.10*
DBAS-10 05 Worried may lose control of sleep 0.22**
DBAS-10 06 Poor sleep will interfere with daytime activities 0.22**
DBAS-10 07 Poor sleep disturbs daytime mood 0.25**
DBAS-10 08 Poor night’s sleep affects the whole week 0.29**
DBAS-10 09 Lack of energy due to poor sleep 0.22**
DBAS-10 10 No control over racing mind 0.43**
DBAS-10 Total
Score 0.38**
*p<0.05; ** p<0.01
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Maladaptive Sleep-Related Behaviors
Normal young adults: Sleep hygiene practices correlated significantly with subjective sleep quality as well as with daytime sleepiness (Brown et al., 2002; Mastin et al., 2006).
Insomnia patients: They were found to engaged in poorer sleep hygiene practices in some studies (Lacks & Rotert, 1986; Kohn & Espie, 2005; Jefferson, 2005), but not in the other studies (Harvey, 2000; McCrae et al., 2006).
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Maladaptive Sleep Hygiene Practice
Insomniac Good Sleeper
t-value pGlass’s
ΔSHPS Scores Mean SD Mean SD
Sleep Schedule 22.64 5.43 21.17 5.79 1.83 .069 .253
Arousal-related
Behavior28.61 6.55 19.39 4.92 11.21 <.001 1.874
Drinking / Eating11.55 4.28 12.29 4.29 -1.21 .228 -.172
Sleep
Environment 18.92 6.24 17.33 5.62 1.87 .064 .283
Total Score 81.73 15.08 70.18 16.45 5.11 <.001 .702
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Maladaptive Sleep Hygiene Practice
ISI PSQI
Insomniacs Control Insomniacs Control
Sleep Schedule .007 .377** .176 .318**
Arousal-related Behavior .326** .610** .248* .533**
Drinking/Eating Habits -.092 .323** -.035 .117
Sleep Environment -.022 .511** -.038 .321**
Total Score .110 .576** .144 .412**
Correlations between sleep hygiene practices and insomnia severity
and sleep quality
* p < .05; ** p < .01
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Psychosocial Factors in
Transient vs. Chronic Insomniacs
假設一
假設二
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假設一結果摘要表
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病因模式路徑圖:慢性失眠
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CLINICAL IMPLICATIONS
睡SLEEP
Pathological Model of Insomnia: An Example
人格特質
生理
亢奮 不當的因應/認知
壓力原 暫時性失眠 長期失眠
認知
亢奮
睡SLEEP
Pathological Model of Insomnia: An Example
人格特質
生理
亢奮 不當的因應/認知
壓力原 暫時性失眠 長期失眠
認知
亢奮
睡SLEEP
NIH 2005 State of the Science Conference Statement
“Behavioral and CBTs have demonstrated efficacy in
RCTs.”
“there are indications that the beneficial effects of CBT,
in contrast to those produced by medications, may last
well beyond the termination of treatment.”
“There is no evidence that such treatment produces
adverse effects, but thus far, there has been little, if
any, study of this possibility.”
“However, because few clinicians are experts in the
use of CBT for the treatment of chronic insomnia,
these techniques are not in widespread use.”
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CBT vs. Hypnotic for Sleep Maintenance Insomnia in Elderly
Morin et al. JAMA 1999; 281:991-999.
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CBT vs. Hypnotic for
Sleep-Onset Insomnia
0
10
20
30
40
50
60
Cha
nges
in
Sle
ep L
aten
cy, %
CBT Combination
Therapy
Pharmacotherapy Placebo
Treatment Condition
Mid-Tx
Post-Tx
(Jacobs, G.D., et al. Ach Intern Medicine 2004;164: 1888-1896)
睡SLEEP
CBT for Insomnia
Understanding
the Pathological
Model of Insomnia
Changes of
Sleep Cognition
Changes of
Sleep Behaviors
Stress Management
& Relaxation
Training
Stabilization &
Adjustment of
Circadian Rhythms
Better
Sleep!!
Hypnotics
Tapering
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Treatment Outcome: ISI
Treatment effect: F = 56.8, p < .001
Group effect: F = .27, p = .77
Interaction: F = 18.15, p < .001
0
5
10
15
20
25
CBT COMB PT
ISI-pre ISI-post
***
***
*** p < .001
睡SLEEP
Questions and Comments?