Science Talk-091012-楊健銘

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由基礎研究到臨床應用----談失眠的病理機制

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Science Talk-091012-楊健銘

  1. 1. SLEEP S 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
  2. 2. 睡 Outline  Neurophysiological Mechanisms of Sleep/Wake Regulation  Neurobehavioral Model of Insomnia SLEEP  Clinical Implications
  3. 3. 睡 NEUROPHYSIOLOGICAL MECHNISMS SLEEP OF SLEEP/WAKE REGULATION
  4. 4. Brain Systems 睡 for Sleep/Wake Regulation “Sleep is of the brain, by the brain and for the brain.” ~ Allan Hobson, 2005, Nature SLEEP
  5. 5. 睡 Neurophysiological Aspects of Sleep/Wake Regulation Homeostatic Two- System process SLEEP model of sleep Sleep regulation Circadian vs. System Wake/Arousal Arousal System
  6. 6. 睡 Neurophysiological Aspects of Sleep/Wake Regulation Homeostatic System SLEEP Sleep Circadian vs. System Wake/Arousal Arousal System
  7. 7. 睡 Homeostatic Regulation of Sleep  The homeostatic sleep drive is determined by the amount of prior sleep and waking/activities. SLEEP
  8. 8. SLEEP 睡
  9. 9. 睡 Neurophysiological Aspects of Sleep/Wake Regulation Homeostatic System SLEEP Sleep Circadian vs. System Wake/Arousal Arousal System
  10. 10. 睡 Free Running Study SLEEP
  11. 11. Forced 睡 SLEEP Desynchrony Protocol 20 hours/”day” Core body temperature & Melatonin rhythms = 24 hrs 15 mins (Czeisler, 2000)
  12. 12. 睡 Intrinsic Circadian Period (Forced desynchrony protocol) 8 Number of subjects 7 6 SLEEP 5 4 Young (n = 11) 3 Older (n = 13) 2 1 0 23.8 23.9 24 24.1 24.2 24.3 24.4 24.5 24.6 Intrinsic circadian period (hours)
  13. 13. 睡 SLEEP Circadian Regulation of Sleep
  14. 14. 睡 Light & Circadian Rhythms  Neural pathway - Melanopsin in ganglion cells of retina - Retinohypothalamic tract SLEEP - SCN  PRC of light on phase shifting
  15. 15. 睡 SLEEP PRC Curve of Light
  16. 16. 睡 Circadian Regulation of Sleep  Genetic control of circadian process SLEEP
  17. 17. 睡 Neurophysiological Aspects of Sleep/Wake Regulation Homeostatic System SLEEP Sleep Circadian vs. System Wake/Arousal Arousal System
  18. 18. 睡 Arousal System  The arousal system does not regulate sleep directly, but may inhibit sleep by promoting waking and arousal. SLEEP  Factors that may trigger arousal: - Sensory stimulus - Emotion and motivation
  19. 19. SLEEP 睡
  20. 20. 睡 NEUROBEHAVIORAL MODEL SLEEP OF INSOMNIA
  21. 21. 睡 Neurophysiological Aspects of Sleep/Wake Regulation Homeostatic System SLEEP Sleep Circadian vs. System Wake/Arousal Arousal System
  22. 22. Homeostatic Regulation 睡 in Insomnia  Neurophysiological findings - Reduced EEG slow wave activity (Merica & Gaillard, 1992) - Reduced brain GABA measured by Proton Magnetic Resonance Spectroscopy (Winkelman et al., SLEEP 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
  23. 23. 睡 Neurophysiological Aspects of Sleep/Wake Regulation Homeostatic System SLEEP Sleep Circadian vs. System Wake/Arousal Arousal System
  24. 24. Circadian Regulation 睡 in Insomnia  Neurophysiological findings - Shifting in circadian phase: Circadian Rhythm Sleep Disorders SLEEP - 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)
  25. 25. 睡 SLEEP A Case of Young Adults Complaining of Insomnia
  26. 26. 睡 週末晚睡晚起的影響研究 延後實驗情境 基準實驗情境 pm am pm am *8:00 10:00 12:00 2:00 4:00 6:00 8:00 10:00 *8:00 10:00 12:00 2:00 4:00 6:00 8:00 10:00 週一至 週四 SLEEP 週五 週六 週日 SSS SSS SSS SSS VAMS VAMS VAMS VAMS Sleep Log Sleep Log Cognitive Tests Cognitive Tests Wake Sleep * The timing indicated is for subjects whose habitual bedtime is 11:00 pm and wake-up time is 7:00 am.
  27. 27. 睡 SSS ratings on Sunday night 6 5 SLEEP 4 Baseline Week SSS Rating 3 Delayed Week 2 1 0 BT-3h BT-2h BT-1h BT-1/2h* BT* BT = bedtime; * p< .05 Time
  28. 28. 睡 Sunday Night Sleep Logs Baseline Delayed Item Mean SD Mean SD t p SLEEP 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
  29. 29. Cognitive Tests 睡 on Monday Morning Controlled Oral Word-list Word Association Memory Test 30 12 SLEEP Number 25 10 of 20 8 Words Baseline Week 15 6 Delayed Week 10 4 5 2 0 0 t = -3.49, p = .002 t = -2.71, p = .011
  30. 30. 睡 Monday Morning Mood 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 SLEEP 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
  31. 31. 睡 Salivary DLMO: After delayed weekend schedule 24.00 #1 23.00 #2 SLEEP #4 Time 22.00 #5 #7 21.00 #11 #12 #16 20.00 #17 #19 19.00 Average Friday Monday
  32. 32. 睡 Neurophysiological Aspects of Sleep/Wake Regulation Homeostatic System SLEEP Sleep Circadian vs. System Wake/Arousal Arousal System
  33. 33. Arousal System 睡 in Insomnia  Physiological hyperarousal, as measured by - CNS activities: e.g. EEG, PET, …… - ANS indices: e.g. heart rate, HRV, VO2, …… SLEEP - Stress related hormones  Psychological/Behavioral Factors - Stress - Emotional disturbances - Cognitive hyperarousal - Conditioning of arousal - Use of stimulants
  34. 34. 睡 SLEEP ERPs in the first 5 min S2 sleep (Yang & Lo, 2007)
  35. 35. 睡 Neurobehavioral Model of Insomnia Psychological/Behavioral Neurophysiological Facotrs Systems Homeostatic SLEEP Behavioral Practices System Sleep Sleep Circadian vs. Cognition System Wake/Arousal Emotional Arousal Arousal System
  36. 36. Cognitive Model of Insomnia 睡 SLEEP (Harvey, 2002)
  37. 37. 睡 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 SLEEP Effect (N = 383) (N = 145) Size* 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.
  38. 38. 睡 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) Correlation with Factor/Item Content the FIRST score DBAS Factor I Beliefs about the immediate negative consequences of insomnia 0.27** SLEEP Beliefs about the long-term negative consequences of insomnia DBAS Factor II 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** Should stay in bed and try harder when having sleep problems DBAS-10 04 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
  39. 39. 睡 Maladaptive Sleep-Related Behaviors  Normal young adults: Sleep hygiene practices correlated significantly with subjective sleep quality as well as with daytime sleepiness SLEEP (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).
  40. 40. 睡 Maladaptive Sleep Hygiene Practice Insomniac Good Sleeper Glass’s SHPS Scores Mean SD Mean SD t-value p Δ SLEEP Sleep Schedule 22.64 5.43 21.17 5.79 1.83 .069 .253 Arousal-related 28.61 6.55 19.39 4.92 11.21 <.001 1.874 Behavior Drinking / Eating 11.55 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
  41. 41. 睡 Maladaptive Sleep Hygiene Practice Correlations between sleep hygiene practices and insomnia severity and sleep quality ISI PSQI SLEEP 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** * p < .05; ** p < .01
  42. 42. 睡 Psychosocial Factors in Transient vs. Chronic Insomniacs 假設一 SLEEP 假設二
  43. 43. 睡 SLEEP 假設一結果摘要表
  44. 44. 睡 SLEEP 病因模式路徑圖:慢性失眠
  45. 45. 睡 SLEEP CLINICAL IMPLICATIONS
  46. 46. Pathological Model of Insomnia: 睡 An Example 人格特質 SLEEP 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
  47. 47. 睡 Pathological Model of Insomnia: An Example 人格特質 SLEEP 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
  48. 48. NIH 2005 State of the Science 睡 Conference Statement  “Behavioral and CBTs have demonstrated efficacy in RCTs.”  “there are indications that the beneficial effects of CBT, SLEEP 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.”
  49. 49. CBT vs. Hypnotic for Sleep 睡 SLEEP Maintenance Insomnia in Elderly Morin et al. JAMA 1999; 281:991-999.
  50. 50. 睡 CBT vs. Hypnotic for Sleep-Onset Insomnia 60 Changes in Sleep Latency, % 50 SLEEP 40 30 Mid-Tx 20 Post-Tx 10 0 CBT Combination Pharmacotherapy Placebo Therapy Treatment Condition (Jacobs, G.D., et al. Ach Intern Medicine 2004;164: 1888-1896)
  51. 51. 睡 CBT for Insomnia Changes of Sleep Cognition Changes of Sleep Behaviors SLEEP Understanding Stabilization & Adjustment of Better the Pathological Model of Insomnia Circadian Rhythms Sleep!! Stress Management & Relaxation Training Hypnotics Tapering
  52. 52. 睡 Treatment Outcome: ISI  Treatment effect: F = 56.8, p < .001  Group effect: F = .27, p = .77  Interaction: F = 18.15, p < .001 SLEEP 25 *** 20 *** 15 ISI-pre ISI-post 10 5 0 CBT COMB PT *** p < .001
  53. 53. 睡 SLEEP Questions and Comments?

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