睡眠 Sleep

1. 睡眠Sleep Professor Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Dec. 24, 2007 Lecture for the 4th class of Dept of Medicine National Yang-Ming University

7. Sleep disturbances

8. 正視失眠問題 • 從流行病學角度來看，保守估計全台灣大約有150~200萬的人飽受失眠之苦 • 由於慢性失眠可能導致的社會問題 • 意外或交通事故 (高四倍) • 個人健康、家庭生活與人際關係的干擾 • 因為注意力及記憶力障礙造成的損失 (慢性失眠者比睡眠良好的人認知功能 表現降低大約20%)

9. How Common Is Insomnia? • Overall prevalence • Symptomatic with consequences • Actually diagnosed • Insomnia symptoms • Overall prevalence 35% Insomnia symptoms with Daytime consequences10%-12% Insomnia diagnosis 6% Adapted from Buysse DJ et al. Primary Psychiatry. 2005;12:37-44.

10. Prevalence of Insomnia 33% 10% Insomnia Symptoms With Daytime Symptoms Sleep Dissatisfaction 15% Insomnia Diagnosis 6 to 9% Ohayon MM. Sleep Med Rev. 2002;6:97-111.

11. A Telephone Survey in 2006 Unit: % 30.0% 24.8% 25.0% 20.2% 20.0% 14.6% 13.5% 13.3% 15.0% 10.0% 5.0% 0.0% TOTAL Interrupted Sleep Difficulty in Initiation Nonrestorative Sleep Early Morning Awakening 【n=4,011】 Taiwan society of sleep medicine, 2006

12. A Telephone Survey in 2006 P < 0.01 13.2% 11.5% 9.9% 【n=4,011】 Taiwan society of sleep medicine, 2006

13. Effect of Sex on the Prevalence of Insomnia by Age 25% 20% 15% 10% 5% 0% Lifetime Prevalence Male Female 40-44 45-54 55-64 65-74 >=75 p < 0.1 6.60% 6.20% 6.90% 10.30% 6.60% 9.20% 9.90% 12.60% + 40-44 45-54 55-64 65-74 >=75 5.50% 5.30% 7% 8.65% 8.40% 5.20% 6.70% 12% 16% 16% 40-44 45-54 55-64 65-74 >=75 Years 30% 25% 20% 15% 10% 5% 0% One-month Prevalence Male Female p < 0.001 ** * * 40-44 45-54 55-64 65-74 >=75 Years

15. DSM-IV Dyssomnia Primary insomnia Restless leg Syndrome (RLS), Periodic limb movement d/o (PLMS) Narcolepsy, Sleep apnea Circadian rhythm sleep d/o Insomnia mixed with hypersomnia Parasomnia Medical, psychiatric, & substance - induced sleep disorders Sleep walking, Sleep terrors Nightmares, REM behavior Bruxism, NPD, enuresis

18. Figure 64-1. Narcoleptic Doberman pinschers in the middle of a cataplectic attack. Note that eyes are open. Autosomal recessive forms of canine narcolepsy are due to mutations in the hypocretin receptor type 2 gene.

19. Sleep Switch: rapid transition From arousal to asleep & vice versa • VLPO: ventrolateral preoptic nuclei • - Inhibitory on arousal system and active during • sleep • - Damage on VLPO---chronic insomnia • - Suppress VLPO --- awakening • - receiving inputs from monoaminergic neurons • - LC, TMN & Raphe nuclei, inhibit VLPO, are • stabilized by orexin in the awake • - Sleep switch has mutually inhibitory elements • - In that, one side shut down the other side and • diminish its own actions and result in abrupt change • from awake to asleep • In the sleep state: • - VLPO inhibit orexin neurons • and LC, TMN & Raphe nuclei • Narcoolepsy • -a problem with such a switch: rapid unwanted • transitions from one state to the another can occur • when it is unstable • - Narcolepsy (2000) had few orexin neurons in the • hypothalamus • - Orexin neurons (hypocretin): active during wakeful- • ness and reinforce the arousal system • - Lost the stabilizing influence on the orexin neurons

20. Neuronal degeneration of orexin neurons in lateral hypothalamus Of a pt with narcolepsy vs. control

21. NarcolepsyThree - stage pathway for control of sleepGreater integration of multiple factors and greater flexibility in behavioral response 3rd system Dorsomedial nu. of hypothalamus (DMH) SCN many physiological Functions: eating, temp & Cortisol cycle are affected. Few direct projections VLPO Orexin neurons

26. Obstructive Sleep Apneain Psychiatry

28. EKG Airflow Thoracic effort Abd. effort SAO2 Obstructive Apnea: A complete blockage of the airway despite efforts to breath. Notice the effort gradually increasing ending in airway opening.

30. Circadian rhythm sleep disorder

39. Melatoniin secretion in the elderly Post-BLTn=10 Pre-BLTn=10 Light therapy Mishima K., Okawa M. et al. J.Clin. Endocrinology Metab., 2001

42. Light therapy for elderly:1.afternoon light 2. duration:2-3 hours3. strength3000-3500 lux

45. Perpetuating Factors • Behavioral • Irregular sleep-wake schedule • Excessive time in bed • Sleep-incompatible activities • Excessive caffeine use, stimulating activities close to bedtime • Clock watching during the night • Cognitive • Worry about sleep • Fear of not sleeping • Irrational beliefs concerning consequences of poor sleep

48. GABAA Receptor Pentamer constructed from 3 types of subunit    Benzodiazepines Binding sites  Chloride channel 

49. Commonly Used BzRA Hypnotics