对失眠认识的进展

对失眠认识的进展

睡眠专家协会（APSS）2005年7月16～23日在美国科罗拉多州(Colorado 位于美国西部)的 丹佛(Denver美国科罗拉多州首府)举行了第19届年会。失眠成焦点议题。针对失眠问题的100个新的各种各样的研究结果在这个大会上发表。

我主要谈谈与睡眠不好相关的各种疾病，并回顾分析澄清 、阐明的一些有关病理生理学和遗传可能性上的问题。

病态的失眠

来自 Science Conference 国立卫生研究院的一些重要结论：

       在大多数病例中，失眠 的存在与其他疾病或精神状态有关。传统上认为，继发于后两者。临床上多倾向认为是一种（单独的）病态（非继发）。有说服力的证据是失眠先于 其他疾病的存在，且常难以治愈。其结果，需要单独治疗。

痛觉过敏

各种各样的痛觉过敏于与失眠相关。

所有的失眠特别是REM丢失的失眠与痛觉过敏有关。

肌纤维痛

乳腺癌

乳腺癌病人的疼痛、
疲乏、 焦急、郁闷等问题和差的生存质量与失眠构恶性循环。

别的病态

如HIV患者。

一些疾病所致的失眠

多种研究发现特定的个体倾向于（易）发生失眠。这种情况下，治疗原发病的同时也还要直接治疗失眠。

失眠的发病

原发性失眠者的在夜间的IL-6高于对照组。提示免疫功能紊乱。

失眠的病理生理学

此方面已引起人们的关注。

经研究脑的局部代谢，发现失眠患者在清醒和非REM睡眠时代谢增加。

失眠遗传吗？

研究者发现在压力相关的失眠者中一级亲属也更易发生失眠，提示与基因易感性有关。类似于IQ.

另外有结论认为：家族史可作为一个诱发因素。

结论

诊断与治疗失眠十分必要。

失眠的治疗不仅仅有利于失眠本身，也有利于并存疾病的好转。

Advances in Understanding the Nature of Insomnia 

The Association of Professional Sleep Societies (APSS) held its 19th annual meeting on June 16-23, 2005, in Denver, Colorado. Insomnia was a major focus at this year's conference; results from 100 new research studies on various aspects of insomnia were presented. In this report I discuss studies that link poor sleep to a variety of comorbid disorders and review research that clarifies the pathophysiology and heritability of insomnia.

Insomnia Comorbidities

Important Conclusions From the Special Session on the National Institutes of Health State of the Science Conference

Conclusions from this symposium, which reviewed the findings of the National Institutes of Health (NIH) State of the Science Conference on Manifestations and Management of Chronic Insomnia in Adults held June 13-15, 2005, at the Natcher Conference Center, NIH, reflect research presented at the APSS on insomnia comorbidities.^[1] One key conclusion of the NIH conference was that, in most cases, insomnia exists in the context of other medical or psychiatric conditions. The panel emphasized that although historically insomnia has been thought to be secondary to these conditions, clinically it is best to consider insomnia to be comorbid with (not secondary to) another condition. This insight acknowledges the fact that insomnia often predates the coexisting condition and/or is refractory to the successful treatment of that condition. Clinically, this suggests that, in addition to the comorbid condition, the insomnia needs to be treated directly to maximize patient outcomes.

Hyperalgesia

A variety of pain conditions are associated with insomnia. A study reported by Hyde and colleagues^[2] found that both the loss of sleep and the specific loss of REM sleep are associated with increased pain sensitivity. These results suggest that REM sleep-related sleep loss and opioids, which suppress REM sleep, might augment pain sensitivity.

Fibromyalgia

This relationship between sleep and pain was also investigated by Edinger and associates^[3] in patients with fibromyalgia. In patients with insomnia comorbid with fibromyalgia, both sleep latency and total sleep time were shown to correlate with daytime ratings of pain, mood, and general mental health. Furthermore, when sleep improved as a consequence of cognitive behavioral therapy, a parallel improvement in these daytime functions occurred. Clearly, the management of fibromyalgia requires the treatment of patients' sleep problems to maximize pain control.

Breast Cancer

Of particular interest this year was research on insomnia comorbid with cancer. One notable study by Rumble and coinvestigators^[4] investigated patients with breast cancer with or without insomnia. Patients with insomnia reported higher levels of daily pain, daily fatigue, anxiety, and depressive symptoms and lower quality of life. Clearly, the cycle of more pain leading to more disturbed sleep leading to greater pain leading to more disturbed sleep demands that clinicians not only treat the pain but also the disturbed sleep.

Other Medical Conditions

Other medical conditions are also comorbid with insomnia. For example, Fins and colleagues^[5] reported on the co-occurrence of insomnia with HIV and the role of cognitive behavioral therapy. Most HIV patients in this study had difficulty inducing and maintaining sleep that was associated with impaired waking function. Similarly, Huang and colleagues^[6] reported that there is a co-occurrence of a circadian rhythm disturbance in 5% to 10% of all insomnia patients.

Implications of Insomnia Comorbidities

Together, this research demonstrates that insomnia is comorbid with another condition in most cases. These various studies suggest that certain individuals are predisposed to insomnia and that these conditions "precipitate" the insomnia not "cause" it. Thus, treatment of the coexisting condition is not adequate, and direct treatment of the insomnia is warranted.

The Morbidity of Insomnia

Another important focus of research this year was further understanding the morbidity of insomnia. The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition and the International Classification of Sleep Disorders both require daytime impairment as part of their criteria for an insomnia diagnosis. Several studies evaluated the consequences of insomnia on a variety of human functions.

Riemann and colleagues^[7] evaluated immune function in patients with primary insomnia and found an elevation in interleukin 6 during the night in patients relative to controls. They concluded that patients with primary insomnia have dysfunctioning immune systems. A population-based study^[8] related insomnia to functional capacity and found a link between insomnia and absenteeism (increase rate of missing work in the last 3 months) and decreased productivity. Importantly, these investigators not only found a difference between patients with insomnia and controls but also were able to demonstrate that within the insomnia population, the more severe the insomnia the greater the degree of impairment.

The same research group also demonstrated that patient reports of insomnia severity (defined as difficulty falling asleep staying asleep or nonrestorative sleep associated with impaired daytime functioning) correlated with a variety of quality-of-life scales, including the 36-item Short-Form Health Survey physical functioning and pain scales.^[9] Interestingly, the most robust correlations with quality of life were related to daytime symptoms rather than nighttime insomnia. This research underscores the conclusions of the NIH panel that insomnia clinical trials need to increasingly focus on daytime functional outcome, not simply nocturnal sleep parameters. Clinical trials of behavioral and pharmacologic therapies need to demonstrate not only reduced sleep latency and increased total sleep time but also diminished pain and improved productivity and quality of life.

In service of that goal, Kuo and Manber^[10] presented a new insomnia functional outcome scale, The Insomnia Impact Questionnaire, which was developed by assessing 65 adverse daytime effects reported to be associated with poor sleep by insomnia patients. Kuo and Manber identified 4 categories of these impairments: emotional distress, physical distress, cognitive ineffectiveness, and fatigue. They concluded that this scale will be a useful tool to evaluate the clinical significance of insomnia treatments.

Pathophysiology of Insomnia

The pathophysiology of insomnia is receiving increasing attention. The finding that patients with insomnia are more alert than controls despite having less sleep and more fragmented sleep at night has led many investigators to speculate that central nervous system hyperarousal is an important component of vulnerability to insomnia. Nofzinger and colleagues^[11] evaluated the regional brain metabolism of patients with insomnia, patients with depression, and healthy controls using [18F]-fluoro-2-deoxyglucose positron emission tomography during both wake and non-REM sleep. Patients with insomnia had increased whole-brain metabolic activity during the wake state and during non-REM sleep. In addition, patients with insomnia had increased metabolic activity in their frontal lobes during the wake state. This may account for or be reflective of the cognitive hyperarousal reported to be present in patients with insomnia. Similarly, the increased metabolic activity observed in the brainstem and midbrain structures of insomnia patients during sleep may be responsible for the amplified physiologic arousal.

To understand the nature of this physiologic arousal, studies have focused on endocrine function. Specifically, hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis has been implicated in this amplified arousal.^[12] In this study, venous samples were assayed for adrenocorticotropic hormone, cortical binding globulin, and dexamethasone levels in patients who had ingested 1.5 mg of dexamethasone the previous evening. Compared with controls, patients with insomnia demonstrated a 71% greater adrenocorticotropic hormone response. The investigators concluded that these data reflect the HPA dysregulation (hyperarousal) seen in primary insomnia.

Results of a clinical study by Edell-Gustafsson and colleagues^[13] support these imaging and HPA data. This group evaluated cognitive hyperarousal in Swedish insomnia patients. They found that patients with insomnia had elevated scores on the hyperarousal behavior trait scale and reactivity measures relative to the general population. The elevation in hyperarousal scores was more pronounced in women than men, a finding consistent with the elevated risk of insomnia among women.

Is Insomnia Inherited?

Another area of interest is the genetic-familial aggregation of insomnia. Scofield and associates^[14] evaluated the responses to the Ford Insomnia Response to Stress Test (FIRST) in 31 randomly selected individuals and their siblings. This scale has been shown to be elevated in individuals with insomnia and individuals who experience disturbed sleep on the first night in a sleep laboratory. These investigators found that FIRST scores were significantly correlated among sibling pairs (r = 0.51; P < .003). Because the FIRST scores were significantly higher in insomnia sibling pairs (ie, when either sibling met diagnostic criteria for insomnia), the correlation was also significant when sibling pairs with insomnia were excluded (r = 0.64; P < .001). The researchers concluded that these data support the notion that stress-related sleep disturbance is more common among first-degree relatives, suggesting a genetic vulnerably to disturbed sleep. They also stated that the level of correlations observed were similar to those reported for the hereditability of IQ.

Another study evaluated family history as a predisposing factor for insomnia.^[15] In a sample of 961 adults, 444 were found to be good sleepers, 266 experienced insomnia symptoms, and 251 met criteria for an insomnia syndrome. Among those who met the diagnostic criteria for insomnia, 45.6% reported having a first-degree relative with insomnia. By contrast, only 32.9% of good sleepers reported having a family member with insomnia. Insomnia was also reported to be more frequent among mothers and sisters, a finding consistent with the higher prevalence of insomnia in women.

Conclusion

The new research on insomnia presented at the APSS annual meeting continues to emphasize the need for improved identification and treatment of insomnia. Specifically, this year's research results emphasize insomnia in the context of other medical and psychiatric disorders. Today we know that insomnia predisposes individuals to many of these disorders and modifies their course. It is believed, but needs to be demonstrated, that insomnia therapy improves not only disturbed sleep but also the comorbid disorders.

References

1. Buysse DJ, Lederhendler I, Roth T, Walsh J, Ancoli-Israel S, White D. Manifestations and management of chronic insomnia in adults: a report from the NIH State of the Science Conference. Program and abstracts of the Associated Professional Sleep Societies 19th Annual Meeting; June 18-23, 2005; Denver, Colorado.
2. Hyde ME, Roehrs TA, Blaisdell B, et al. REM sleep deprivation produces hyperalgesia. Program and abstracts of the Associated Professional Sleep Societies 19th Annual Meeting; June 18-23, 2005; Denver, Colorado. Abstract 0377.
3. Edinger JD, Wohlgemuth WK, Krystal AK, Rice JR. Behavioral insomnia therapy for fibromyalgia: final report. Program and abstracts of the Associated Professional Sleep Societies 19th Annual Meeting; June 18-23, 2005; Denver, Colorado. Abstract 0667.
4. Rumble M, Edinger JD, Keefe FJ, et al. A pilot study examining the utility of the cognitive-behavioral model of insomnia in early stage breast cancer patients. Program and abstracts of the Associated Professional Sleep Societies 19th Annual Meeting; June 18-23, 2005; Denver, Colorado. Abstract 0678.
5. Fins A, Hardy M, Baker T, et al. Cognitive behavioral therapy for HIV-related insomnia. Program and abstracts of the Associated Professional Sleep Societies 19th Annual Meeting; June 18-23, 2005; Denver, Colorado. Abstract 0699.
6. Huang JS, Ong JC, Kuo TF, Manber R. Morningness/eveningness and CBT for insomnia. Program and abstracts of the Associated Professional Sleep Societies 19th Annual Meeting; June 18-23, 2005; Denver, Colorado. Abstract 0674.
7. Riemann D, Burgos I, Richter L, et al. Nocturnal interleukin-6 (IL-6) and leptin excretion in patients with primary insomnia. Program and abstracts of the Associated Professional Sleep Societies 19th Annual Meeting; June 18-23, 2005; Denver, Colorado. Abstract 0676.
8. Daley ME, LeBlanc M, Morin CM. The impact of insomnia on absenteeism, productivity, and accident rates. Program and abstracts of the Associated Professional Sleep Societies 19th Annual Meeting; June 18-23, 2005; Denver, Colorado. Abstract 0735.
9. Vallieres A, Belleville G, Edell-Gustafsson U, Morin CM. Correlates of health-related quality of life in primary insomnia. Program and abstracts of the Associated Professional Sleep Societies 19th Annual Meeting; June 18-23, 2005; Denver, Colorado. Abstract 0687.
10. Kuo TF, Manber R. Assessment of daytime sequelae of poor sleep: the Insomnia Impact Questionnnaire (IIQ). Program and abstracts of the Associated Professional Sleep Societies 19th Annual Meeting; June 18-23, 2005; Denver, Colorado. Abstract 0692.
11. Nofzinger EA, Buysse DJ, Germain A, et al. A comparison of regional cerebral metabolism across waking and NREM sleep between primary insomnia and major depression. Program and abstracts of the Associated Professional Sleep Societies 19th Annual Meeting; June 18-23, 2005; Denver, Colorado. Abstract 0691.
12. Richardson GS, McClure TK, Meola G, Roth T. Dex-CRH test in primary insomnia. Program and abstracts of the Associated Professional Sleep Societies 19th Annual Meeting; June 18-23, 2005; Denver, Colorado. Abstract 0763.
13. Edell-Gustafsson U. Hyperarousal behavioural trait, sufficient sleep index and health related quality of life. Program and abstracts of the Associated Professional Sleep Societies 19th Annual Meeting; June 18-23, 2005; Denver, Colorado. Abstract 0703.
14. Scofield H, Drake C, Myers E, et al. Familial vulnerability to sleep disturbance. Program and abstracts of the Associated Professional Sleep Societies 19th Annual Meeting; June 18-23, 2005; Denver, Colorado. Abstract 0711.
15. Beaulieu-Bonneau S, LeBlanc M, Morin CM. Family incidence as a predisposing factor of insomnia. Program and abstracts of the Associated Professional Sleep Societies 19th Annual Meeting; June 18-23, 2005; Denver, Colorado. Abstract 0673.