臺灣博碩士論文加值系統

背景與目標：失眠診斷中依其症狀可分成不同亞型，包括入睡困難、睡眠片段、清晨早醒及混合型。失眠與生理過度興奮有關，研究中也發現失眠者有自律神經調節異常的現象，但過去研究大多將所有慢性失眠者綜合起來討論，而未將失眠依症狀加以區分探討，使失眠的成因難以有更深入的了解，本研究目標為探討不同失眠亞型者自律神經系統調控的差異。研究方法：研究招募慢性失眠者、睡眠良好者及藥物治療中失眠患者於晚間至睡眠研究室配戴自製微型多頻道生理紀錄儀後返家進行居家睡眠記錄，並分析其睡眠期間的各腦波波段頻譜及心率變異性。結果：入睡困難型失眠者在整個睡覺的過程特別是在入睡前有交感神經過度活化的現象；睡眠片段型失眠者，特別是每次醒來後難以再度入睡的患者，在睡眠過程中有交感神經系統過度活化、副交感神經系統活性較低的現象；慢性失眠者於客觀睡眠檢查不符合失眠定義者歸類為非客觀定義失眠組，其在睡眠過程中同樣有交感神經系統過度活化的現象；睡眠品質良好的藥物治療中失眠患者其在睡眠過程中有交感神經系統過度活化、副交感神經系統活性較低的失衡現象。結論：入睡困難型失眠者入睡前交感神經系統過度活化的現象與入睡的發生有關；睡眠片段型失眠者，特別是每次醒來後難以在度入睡的患者，除了在睡覺過程中交感神經系統活性過度活化，副交感神經系統活性較低的現象可能與睡眠的穩定性有關；非客觀定義失眠組睡覺過程中皆有交感神經系統過度活化的現象，顯示此類型失眠者雖然仍有較良好的睡眠品質，心率變異性已出現不良的影響；藥物治療中失眠患者在服用藥物後雖改善了睡眠品質，但自律神經功能已嚴重失衡。

Background: Insomnia is defined as difficulty initiating sleep, difficulty maintaining sleep or waking up earlier than desired. Numerous studies have reported that objective short sleep duration has been characterized by the presence of physiological hyperarousal, it suggests that impaired cardiac autonomic modulation may be the underlying mechanisms leading to adverse health outcomes. However, previous studies mostly combined different insomnia symptoms as the same condition, which made insomnia patients hard to achieve optimal treatment. The present study aimed to examine the differences in the autonomic regulation among different insomnia subtypes.
Methods: Participants were 20 to 35 years old good sleepers (GS), chronic insomniacs and insomniacs in pharmacologic treatment. Subjective measures was based on sleep-related questionnaires and visual analogue scale. The participants in the present study were divided into insomnia subtypes by objective sleep duration, which was based on miniature polysomnography (PSG) for one night after adaptation at home. Electrocardiogram data derived from miniature PSG were used to obtain heart rate variability (HRV). HRV measures included high-frequency (HF) component, an index of parasympathetic activation, and normalized low frequency (LF%), an index of sympathetic activity.
Results: Participants in sleep-onset insomnia (SOI) group had significantly higher LF% during total time in bed (TIB) especially before sleep onset. Sleep-maintenance insomniacs (MI), especially for patients who are difficult to fall asleep again, had elevated LF% power , and reduced HF during TIB. Neither criteria (NC) group was the majority of chronic insomniacs, while their sleep duration doesn’t meet the criteria of insomnia, had higher LF% during TIB. Insomniacs with hypnotic use had high-quality sleep, elevated LF% power, and reduced HF during TIB.
Conclusion: Significant autonomic dysfunction were observe in total insomnia subject in spite of NC group and hypnotic medication patients having higher sleep quality. Our results also indicated that autonomic dysfunction affect the occurrence of falling asleep in SOI. The dysregulation of parasympathetic activity in MI is related to the stability of sleep.

目錄
誌謝 I
中文摘要 II
Abstract III
目錄 IV
第一章 研究背景 1
1-1失眠 1
1-2睡眠分析 1
1-3睡眠異常的主客觀研究 3
1-4自律神經系統對心臟的神經性調控 3
1-5心率變異性 4
1-6睡眠異常與心率變異性 5
第二章 研究假說與目的 7
2-1研究假說 7
2-2研究目的 7
2-3重要性 7
第三章 研究方法 8
3-1研究參與者 8
3-2實驗流程 9
3-3研究工具 10
3-4分析方法 11
第四章 研究結果 14
4-1 參與者基本資料與主觀評量 14
4-2主觀感受與客觀生理參數的相關性 15
4-3慢性失眠者於睡眠各期之心率變異性及腦波比較 16
4-6藥物治療中失眠患者於睡眠各期心率變異性及腦波比較 17
第五章 討論 19
5-1本研究的重要發現 19
5-2不同失眠亞型主觀評量與客觀生理參數相關性 19
5-3不同失眠亞型對於自律神經的影響 19
5-4不同失眠亞型對於腦波的影響 21
5-5安眠類藥物治療對於患者自律神經及腦波的影響 21
5-6本研究限制及未來展望 22
結論 23
參考文獻 24
附表 27
表一、受試者基本資料表 27
表二、不同失眠亞型者主觀問卷分述及客觀睡眠檢查結果比較 29
表三、主觀睡眠感受與客觀睡眠品質的相關性 31
附圖 41
附錄-人體試驗許可證明 58
附錄-問卷 60


圖表目錄
表一、受試者基本資料表 27
表二、不同失眠亞型者主觀問卷分述及客觀睡眠檢查結果比較 29
表三、主觀睡眠感受與客觀睡眠品質的相關性 31
表四、主觀睡眠感受與心率變異性的相關性 32
圖一、實驗流程圖 41
圖二、微型無線多頻道生理紀錄儀 42
圖三、實驗篩選與檢測 43
圖四、慢性失眠者與睡眠良好者於睡眠各期之心率變異性及腦波活性參數比較 45
圖五、入睡困難型失眠者與睡眠良好者於睡眠各期之心率變異性及腦波活性參數比較 47
圖六、睡眠片段型失眠者與睡眠良好者於睡眠各期之心率變異性及腦波活性參數比較 49
圖七、睡眠片段中不同亞型失眠者與睡眠良好者於睡眠各期之心率變異性及腦波活性參數比較 51
圖八、非客觀定義型失眠者與睡眠良好者於睡眠各期之心率變異性及腦波活性參數比較 53
圖九、藥物治療中失眠患者、睡眠良好者、慢性失眠者於睡眠各期之心率變異性及腦波活性參數比較 55
圖十、藥物治療有效失眠患者、睡眠良好者、慢性失眠者於睡眠各期之心率變異性及腦波活性參數比較 57

1. Baglioni, C., W. Regen, A. Teghen, K. Spiegelhalder, B. Feige, C. Nissen and D. Riemann (2014). "Sleep changes in the disorder of insomnia: a meta-analysis of polysomnographic studies." Sleep medicine reviews 18(3): 195-213.
2. Baharav, A., S. Kotagal, V. Gibbons, B. Rubin, G. Pratt, J. Karin and S. Akselrod (1995). "Fluctuations in autonomic nervous activity during sleep displayed by power spectrum analysis of heart rate variability." Neurology 45(6): 1183-1187.
3. Beck, A. T., N. Epstein, G. Brown and R. A. Steer (1988). "An inventory for measuring clinical anxiety: psychometric properties." J Consult Clin Psychol 56(6): 893-897.
4. Beck, A. T., C. H. Ward, M. Mendelson, J. Mock and J. Erbaugh (1961). "An inventory for measuring depression." Arch Gen Psychiatry 4: 561-571.
5. Bonnet, M. H. and D. Arand (1998). "Heart rate variability in insomniacs and matched normal sleepers." Psychosomatic medicine 60(5): 610-615.
6. Bonnet, M. H., G. G. Burton and D. L. Arand (2014). "Physiological and medical findings in insomnia: implications for diagnosis and care." Sleep Med Rev 18(2): 111-122.
7. Buysse, D. J., C. F. Reynolds, T. H. Monk, S. R. Berman and D. J. Kupfer (1989). "The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research." Psychiatry research 28(2): 193-213.
8. Cardiology, T. F. o. t. E. S. o. (1996). "Heart rate variability, standards of measurement, physiological interpretation, and clinical use." circulation 93: 1043-1065.
9. Carney, C. E., D. J. Buysse, S. Ancoli-Israel, J. D. Edinger, A. D. Krystal, K. L. Lichstein and C. M. Morin (2012). "The consensus sleep diary: standardizing prospective sleep self-monitoring." Sleep 35(2): 287-302.
10. Cellini, N., M. de Zambotti, N. Covassin, M. Sarlo and L. Stegagno (2014). "Working memory impairment and cardiovascular hyperarousal in young primary insomniacs." Psychophysiology 51(2): 206-214.
11. Corsi-Cabrera, M., P. Figueredo-Rodríguez, Y. del Río-Portilla, J. Sánchez-Romero, L. Galán and J. Bosch-Bayard (2012). "Enhanced frontoparietal synchronized activation during the wake-sleep transition in patients with primary insomnia." Sleep 35(4): 501-511.
12. de Zambotti, M., N. Covassin, G. De Min Tona, M. Sarlo and L. Stegagno (2011). "Sleep onset and cardiovascular activity in primary insomnia." J Sleep Res 20(2): 318-325.
13. Edition, F. (2013). Diagnostic and statistical manual of mental disorders, Am Psychiatric Assoc.
14. Horne, J. A. and O. Ostberg (1976). "A self-assessment questionnaire to determine morningness-eveningness in human circadian rhythms." Int J Chronobiol 4(2): 97-110.
15. Iber, C. (2007). "Respiratory Rules." The AASM manual for the scoring of sleep and associated events: rules, terminology and technical specifications: 45-50.
16. Iber, C. and C. Iber (2007). The AASM manual for the scoring of sleep and associated events: rules, terminology and technical specifications, American Academy of Sleep Medicine Westchester, IL.
17. Javaheri, S. and S. Redline (2017). "Insomnia and risk of cardiovascular disease." Chest 152(2): 435-444.
18. Jiang, X.-l., Z.-g. Zhang, C.-P. Ye, Y. Lei, L. Wu, Y. Zhang, Y.-y. Chen and Z.-j. Xiao (2015). "Attenuated or absent HRV response to postural change in subjects with primary insomnia." Physiology & behavior 140: 127-131.
19. Johns, M. W. (1991). "A new method for measuring daytime sleepiness: the Epworth sleepiness scale." Sleep 14(6): 540-545.
20. Kuo, T. B., C. Chen, Y.-C. Hsu and C. C. Yang (2012). "Performance of the frequency domain indices with respect to sleep staging." Clinical Neurophysiology 123(7): 1338-1345.
21. Kuo, T. B., T. Lin, C. C. Yang, C. L. Li, C. F. Chen and P. Chou (1999). "Effect of aging on gender differences in neural control of heart rate." Am J Physiol 277(6): H2233-2239.
22. Kuo, T. B., F.-Z. Shaw, C. J. Lai and C. C. Yang (2008). "Asymmetry in sympathetic and vagal activities during sleep-wake transitions." Sleep 31(3): 311-320.
23. Kuo, T. B., F. Z. Shaw, C. J. Lai, C. W. Lai and C. C. Yang (2004). "Changes in sleep patterns in spontaneously hypertensive rats." Sleep 27(3): 406-412.
24. Kuo, T. B. and C. C. Yang (2009). "Frequency domain analysis of electrooculogram and its correlation with cardiac sympathetic function." Experimental neurology 217(1): 38-45.
25. Levenson, J. C., D. B. Kay and D. J. Buysse (2015). "The pathophysiology of insomnia." Chest 147(4): 1179-1192.
26. Meng, L., Y. Zheng and R. Hui (2013). "The relationship of sleep duration and insomnia to risk of hypertension incidence: a meta-analysis of prospective cohort studies." Hypertens Res 36(11): 985-995.
27. Miller, C. B., D. J. Bartlett, A. E. Mullins, K. L. Dodds, C. J. Gordon, S. D. Kyle, J. W. Kim, A. L. D'Rozario, R. S. Lee, M. Comas, N. S. Marshall, B. J. Yee, C. A. Espie and R. R. Grunstein (2016). "Clusters of Insomnia Disorder: An Exploratory Cluster Analysis of Objective Sleep Parameters Reveals Differences in Neurocognitive Functioning, Quantitative EEG, and Heart Rate Variability." Sleep 39(11): 1993-2004.
28. Morin, C. M., G. Belleville, L. Bélanger and H. Ivers (2011). "The Insomnia Severity Index: psychometric indicators to detect insomnia cases and evaluate treatment response." Sleep 34(5): 601-608.
29. Morin, C. M. and R. Benca (2012). "Chronic insomnia." The Lancet 379(9821): 1129-1141.
30. Morin, C. M., R. R. Bootzin, D. J. Buysse, J. D. Edinger, C. A. Espie and K. L. Lichstein (2006). "Psychological and behavioral treatment of insomnia: update of the recent evidence (1998–2004)." Sleep 29(11): 1398-1414.
31. Ohayon, M. M. and C. F. Reynolds (2009). "Epidemiological and clinical relevance of insomnia diagnosis algorithms according to the DSM-IV and the International Classification of Sleep Disorders (ICSD)." Sleep medicine 10(9): 952-960.
32. Pillai, V., T. Roth and C. L. Drake (2015). "The nature of stable insomnia phenotypes." Sleep 38(1): 127-138.
33. Rechtschaffen, A. (1968). "A manual for standardized terminology, techniques and scoring system for sleep stages in human subjects." Brain information service.
34. Siu, A. L. (2015). "Screening for high blood pressure in adults: US Preventive Services Task Force recommendation statement." Annals of internal medicine 163(10): 778-786.
35. Spiegelhalder, K., L. Fuchs, J. Ladwig, S. D. Kyle, C. Nissen, U. Voderholzer, B. Feige and D. Riemann (2011). "Heart rate and heart rate variability in subjectively reported insomnia." Journal of sleep research 20(1pt2): 137-145.
36. Spiegelhalder, K., L. Fuchs, J. Ladwig, S. D. Kyle, C. Nissen, U. Voderholzer, B. Feige and D. Riemann (2011). "Heart rate and heart rate variability in subjectively reported insomnia." J Sleep Res 20(1 Pt 2): 137-145.
37. Spiegelhalder, K., W. Regen, B. Feige, J. Holz, H. Piosczyk, C. Baglioni, D. Riemann and C. Nissen (2012). "Increased EEG sigma and beta power during NREM sleep in primary insomnia." Biological psychology 91(3): 329-333.
38. Thomas, S. J. and D. Calhoun (2017). "Sleep, insomnia, and hypertension: current findings and future directions." Journal of the American Society of Hypertension 11(2): 122-129.
39. Trinder, J., J. Kleiman, M. Carrington, S. Smith, S. Breen, N. Tan and Y. Kim (2001). "Autonomic activity during human sleep as a function of time and sleep stage." J Sleep Res 10(4): 253-264.
40. Tsai, H.-J., T. B. Kuo, Y.-C. Lin and C. C. Yang (2015). "The association between prolonged sleep onset latency and heart rate dynamics among young sleep-onset insomniacs and good sleepers." Psychiatry research 230(3): 892-898.
41. Vgontzas, A. N., J. Fernandez-Mendoza, D. Liao and E. O. Bixler (2013). "Insomnia with objective short sleep duration: the most biologically severe phenotype of the disorder." Sleep medicine reviews 17(4): 241-254.
42. Vgontzas, A. N., J. Fernandez-Mendoza, D. Liao and E. O. Bixler (2013). "Insomnia with objective short sleep duration: the most biologically severe phenotype of the disorder." Sleep Med Rev 17(4): 241-254.
43. Yaggi, H. K., A. B. Araujo and J. B. McKinlay (2006). "Sleep duration as a risk factor for the development of type 2 diabetes." Diabetes care 29(3): 657-661.
44. Yang, A. C., S.-J. Tsai, C.-H. Yang, C.-H. Kuo, T.-J. Chen and C.-J. Hong (2011). "Reduced physiologic complexity is associated with poor sleep in patients with major depression and primary insomnia." Journal of affective disorders 131(1-3): 179-185.
45. Yang, C. C., C.-W. Lai, H. Y. Lai and T. B. Kuo (2002). "Relationship between electroencephalogram slow-wave magnitude and heart rate variability during sleep in humans." Neuroscience letters 329(2): 213-216.
46. Yang, C. C., F. Z. Shaw, C. J. Lai, C. W. Lai and T. B. Kuo (2003). "Relationship between electroencephalogram slow-wave magnitude and heart rate variability during sleep in rats." Neurosci Lett 336(1): 21-24.