Elsevier

Sleep Medicine Reviews

Volume 14, Issue 1, February 2010, Pages 9-15
Sleep Medicine Reviews

Clinical review
Hyperarousal and insomnia: State of the science

https://doi.org/10.1016/j.smrv.2009.05.002Get rights and content

Summary

In the past few years it has become increasingly clear that insomnia is a chronic disease that interacts with many other medical conditions. As our ability to examine complex physiological activity during sleep has increased, additional evidence continues to suggest that insomnia is associated with inappropriate physiological arousal. It is now known that patients with primary insomnia have increased high-frequency EEG activation, abnormal hormone secretion, increased whole body and brain metabolic activation, and elevated heart rate and sympathetic nervous system activation during sleep. This activation can be measured throughout the day and night and is chronic. Other research suggests that insomnia, probably based upon the associated chronic physiologic arousal, is associated with increased risk for medical disorders such as depression, hypertension, or cardiac disease. An animal model that has used odor stress to produce poor sleep in rats has identified specific activated brain sites similar to those found in human brain metabolic studies to suggest that insomnia is a state in which sleep and arousal systems are both simultaneously active. The animal studies have also shown that the inappropriate arousal can be blocked by lesions in the limbic and arousal systems. It is hoped that these findings can be extended to identify new compounds that improve insomnia by acting at these sites of abnormal brain activation.

Section snippets

Evidence for physiological arousal in patients with primary insomnia

Extensive physiological differences between good and poor sleepers were first reported by Monroe,4 who found increased rectal temperature, heart rate, basal skin resistance, and phasic vasoconstrictions 30 minutes prior to and during sleep in poor sleepers as compared to normal sleepers. In the 20 years that followed, several additional differences were reported when patients with insomnia were compared with normal sleepers. Poor sleepers had increased secretion of corticosteroids and adrenaline,

Animal model

The diagnosis of insomnia is based upon the subjective complaint of poor sleep that is sometimes corroborated by EEG recordings. The requirement of a complaint, of course, makes an animal model of insomnia difficult, but studies of poor sleep in animals in response to expected stressors can add unique insight to human work. In a recent model, rats were placed in a cage previously occupied by a male rat (odor exposure). This is a species specific model that produces an acute stress response.

Genetic studies

Basal level of sympathetic nervous system activity, like many other attributes, could be seen as normally distributed in the population. This would mean that some individuals would probably have a genetic predisposition to greater sympathetic activation and therefore a greater predisposition to develop associated disorders such as insomnia. A good deal of evidence suggests that insomnia is under strong genetic influence.66 A recent twin study showed a heritability estimate of 57% for insomnia

Cause versus effect

Despite the fact that there is now pervasive evidence of physiological arousal in numerous systems during sleep in patients with insomnia, none of the literature cited, except, perhaps the rat stress-induced model, comments on causality. Insomnia is typically accompanied by numerous changes including cognitive arousal/stress, dysphoria or degraded mood, depression or anxiety and fatigue in addition to the numerous physiological changes described previously. It has always been difficult to

Medical implications of hyperarousal

Insomnia has been considered an acute disorder often secondary to other medical pathology such as depression or pain. However, more recently an NIH review of insomnia and treatments has concluded that insomnia can be a primary or comorbid chronic disorder.79 Many studies have shown that insomnia is a predictor for the later development of depression.80 In addition, much evidence has accumulated showing abnormal levels of arousal in patients with depression and other mood disorders.81

Treatment of hyperarousal as treatment for insomnia

Although the concept of physiological arousal as a basis for insomnia dates to early studies of poor sleep,4 treatment strategies have continued to focus on changes in EEG sleep latency and sleep efficiency. Relatively few studies have documented changes in other physiological measures with therapy and even fewer have attempted therapies that target the entire night and day. It is known that benzodiazepines, for example, directly decrease metabolic rate87 and body temperature88 and therefore

Summary

In the last few years, increasingly sensitive measures of central nervous system function have provided a much clearer view of the neurophysiology of insomnia both in man and in newly developing animal models. These new data strongly support the view that primary insomnia is a true conflict between the sleep system and inappropriate activation of central nervous system. Identification of specific sites of brain activation with lesion study confirmation should allow development of increasingly

Acknowledgements

Supported by the Dayton Department of Veterans Affairs Medical Center, Wright State University School of Medicine, and the Sleep–Wake Disorders Research Institute.

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