Elsevier

Sleep Medicine Reviews

Volume 17, Issue 4, August 2013, Pages 241-254
Sleep Medicine Reviews

Theoretical review
Insomnia with objective short sleep duration: The most biologically severe phenotype of the disorder

https://doi.org/10.1016/j.smrv.2012.09.005Get rights and content

Summary

Until recently, the association of chronic insomnia with significant medical morbidity was not established and its diagnosis was based solely on subjective complaints. We present evidence that insomnia with objective short sleep duration is the most biologically severe phenotype of the disorder, as it is associated with cognitive-emotional and cortical arousal, activation of both limbs of the stress system, and a higher risk for hypertension, impaired heart rate variability, diabetes, neurocognitive impairment, and mortality. Also, it appears that objective short sleep duration is a biological marker of genetic predisposition to chronic insomnia. In contrast, insomnia with objective normal sleep duration is associated with cognitive-emotional and cortical arousal and sleep misperception but not with signs of activation of both limbs of the stress system or medical complications. Furthermore, the first phenotype is associated with unremitting course, whereas the latter is more likely to remit. We propose that short sleep duration in insomnia is a reliable marker of the biological severity and medical impact of the disorder. Objective measures of sleep obtained in the home environment of the patient would become part of the routine assessment of insomnia patients in a clinician's office setting. We speculate that insomnia with objective short sleep duration has primarily biological roots and may respond better to biological treatments, whereas insomnia with objective normal sleep duration has primarily psychological roots and may respond better to psychological interventions alone.

Section snippets

Insomnia-scope of the problem

Despite the evidence that insomnia, the most common sleep disorder,1 has significant public health implications, including impaired occupational performance, increased absenteeism at work, higher health care costs, and worse quality of life,2 the connection of insomnia to medical morbidity, i.e., cardiometabolic risks, is not established, and this leads some physicians, including sleep researchers, to view insomnia and the associated complaints of poor mental and physical health as obsessions

Subjective sleep measures in the evaluation and treatment of insomnia

Self-reported quantitative assessment of various dimensions of sleep has been used in research and clinical practice for many years, and sleep diaries, for one to two weeks, are recommended as essential measures in insomnia research.6 Current quantitative diagnostic criteria for insomnia that are considered the most defensible include sleep onset latency or wakefulness after sleep onset of more than 30 min.7 However, individuals with insomnia tend to overestimate time to fall asleep or time of

Objective sleep measures in the evaluation and treatment of insomnia

The sleep laboratory is essential for the evaluation of patients with sleep disordered breathing (SDB) and the diagnosis of narcolepsy,8 and in the differential diagnosis of idiopathic vs. psychogenic hypersomnia.9 In addition, sleep laboratory measurements provide valuable objective information on the initial effectiveness, continued efficacy or tolerance, and potential withdrawal effects of a hypnotic drug.

With the disorder of insomnia, the usefulness of the sleep laboratory has been at best

Insomnia with objective short sleep duration is associated with activation of both limbs of the stress system

Stress has been associated with the activation of the HPA axis and the sympatho-adrenal-medullary axis, whereas corticotropin-releasing hormone (CRH) and cortisol (products of the hypothalamus and adrenals, respectively), and catecholamines (products of the sympathetic system) are known to cause arousal and sleeplessness to humans and animals. On the other hand sleep and particularly deep sleep has an inhibitory effect on the stress system including its main two components, the HPA axis and the

Insomnia with objective short sleep duration is associated with medical morbidity and mortality

Many studies have established that insomnia is highly comorbid with psychiatric disorders and is a risk factor for the development of depression, anxiety, and suicide.1 However, in contrast to the other most common sleep disorder, SDB, chronic insomnia has not been linked firmly with significant medical morbidity, e.g., cardiovascular disorders. Several questionnaire-based studies have shown a significant relationship between difficulty falling asleep or poor sleep and cardiac outcomes (see

Insomnia with objective short sleep duration: a disorder of sleep loss or of physiological hyperarousal?

The findings of the physiological studies and of the epidemiological studies that suggest that insomnia with objective short sleep duration is associated with activation of both limbs of the stress system and significant cardiometabolic morbidity and mortality raise the question whether this type of insomnia is a disorder of sleep loss or of physiological hyperarousal. Data from several physiological domains support the latter.

For example, insomniacs complain that they are fatigued and sleepy

Role of objective short sleep duration in the natural history of insomnia and poor sleep

The prevalence of insomnia varies widely among epidemiologic studies ranging from 8 to 40%. A possible explanation for this wide variability is the different criteria used to define insomnia. For example, approximately 8–10% of the general population suffers from chronic insomnia,55, 108, 109 whereas another 20–30% of the population has insomnia symptoms, i.e., difficulties initiating sleep, difficulties maintaining sleep, early morning awakening, and/or non-restorative sleep, at any given time.

Objective sleep duration, sleep misperception, and psychological profiles

According to the DSM-IV, individuals with chronic insomnia complain of sleep difficulties and frequently underestimate their sleep duration.3 Some investigators in the field of insomnia consider the underestimation of sleep duration a trait feature of all insomniacs, in which extreme cases might exist,113 whereas others suggest that a more severe small subgroup of chronic insomnia patients who consistently underestimate their sleep duration deserves a separate diagnostic category.114 This

Further evidence that insomnia with short sleep duration is the most severe phenotype of the disorder: heart rate variability, type 2 diabetes, and depression

Following our studies, there have been several reports with findings consistent with our model that insomnia plus objective short sleep duration has a significant effect on physical and mental health. Specifically, Spiegelhalder et al.125 published a study in which they determined the association of primary insomnia with heart rate and heart rate variability. Fifty-eight patients with primary insomnia and 46 healthy controls participated in the study. The study failed to show a difference in

Habitual sleep duration and night-to-night variability

In our studies, PSG-measured sleep duration is a strong predictor of HPA axis hyperactivity or medical morbidity among insomniacs.16, *17, *56, *59, *61, *78 One of the frequent criticisms of our epidemiological studies is that objective sleep duration was based on one night of PSG, which may not be representative of the subjects' habitual sleep duration. It should be noted that these studies investigated the relative sleep duration measured objectively (i.e., <6 h of objective sleep is

Other polysomnographic variables as potential markers of the biological severity of insomnia

In our studies we have primarily focused on objective sleep duration as a marker of the biological severity of insomnia because cortisol levels, the main output of the stress system, showed their strongest association with short sleep duration.16, *17 We have not systemically looked into other variables such as sleep latency or WASO. In our preliminary study on chronic insomnia and activity of the stress system, we reported that, for example, there was a significant correlation between WASO

Phenotyping insomnia: diagnosis and treatment implications

The field of sleep disorders medicine has attempted to define subgroups within insomnia based on etiology (i.e., primary versus secondary), age of onset (i.e., childhood versus adulthood), and discrepancy in objective versus subjective sleep findings.4 However, these subtypes show poor diagnostic reliability and have not been proven to be useful in terms of their impact on health or specific treatment outcomes.13, 138, 139

The studies presented in this review have led us to suggest two

Acknowledgments

This research was in part funded by the National Institutes of Health grants R01 51931, R01 40916 and R01 64415. The work was performed at the Sleep Research and Treatment Center at the Penn State University Milton Hershey Hospital, and the staff is especially commended for their efforts.

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