Glucose clearance was 40 percent slower with sleep loss than with sleep recovery. Further, mice that have a mutation in a gene that regulates circadian rhythms have metabolic disorders Turek et al. The association between sleep loss and diabetes or impaired glucose tolerance may mediate the relationship between sleep loss and cardiovascular morbidity and mortality, as discussed below.

Sleep loss and sleep complaints are associated with heart attacks myocardial infarction and perhaps stroke, according to several large epidemiological studies Eaker et al.

One of these studies, of incident cases of heart attacks in the Nurses Health Study, was discussed earlier because it also found increased incidence of diabetes Ayas et al. The cohort had no coronary heart disease at baseline. Ten years later, in , the likelihood of nonfatal and fatal heart attack was modestly increased for both short and long sleep duration.

Similarly elevated risks were also found for sleeping 9 hours or more. The effects were independent of a history of hypertension or diabetes because additional adjustment for these conditions yielded slightly lower, but still significantly elevated, relative risks. Several potential mechanisms could explain the link between sleep loss and cardiovascular events, including blood pressure increases, sympathetic hyperactivity, or impaired glucose tolerance.

Experimental data, showing that acute sleep loss 3. Sleep loss is associated with adverse effects on mood and behavior. Adults with chronic sleep loss report excess mental distress, depressive symptoms, anxiety, and alcohol use Baldwin and Daugherty, ; Strine and Chapman, ; Hasler et al.

A meta-analysis of 19 original articles found that partial sleep deprivation alters mood to an even greater extent that it does cognitive or motor functions Pilcher and Huffcutt, Several studies of adolescents, including one with more than 3, high school students, found that inadequate sleep is associated with higher levels of depressed mood, anxiety, behavior problems, alcohol use Carskadon, ; Morrison et al.

Nevertheless, it is not clear from cross-sectional studies whether sleep influences mood or anxiety level, or vice versa. On the other hand, a large, 3-year longitudinal study of more than 2, middle school students ages 11 to 14 found that self-reported sleep loss was associated with more depressive symptoms and lower self-esteem over time Fredriksen et al.

Therefore, although this study suggests an association, the evidence is still limited. Sleep loss is also associated with increased age-specific mortality, according to three large, population-based, prospective studies Kripke et al.

The studies were of large cohorts, ranging from 83, to 1. In three studies, respondents were surveyed about their sleep duration, and then they were followed for periods ranging from 6 to 14 years.

Deaths in short or long sleepers were compared with those who slept 7 hours the reference group , after adjusting for numer ous health and demographic factors. Sleeping 5 hours or less increased mortality risk, from all causes, by roughly 15 percent.

The largest American study, depicted in Figure , graphically illustrates what has been found in all three studies: a U-shaped curve, showing that progressively shorter or longer sleep duration is associated with greater mortality. Other epidemiological studies suggest that sleep-loss-related mortality is largely from acute heart attacks et al.

Potential pathophysiological mechanisms accounting for the relationship, while poorly understood, have become the focus of growing interest and are discussed later in this chapter. Shorter or longer sleep duration is associated with greater mortality.

Management and treatment of sleep loss are rarely addressed by clinicians, despite the large toll on society Chapters 4 , 5 , and 7. There are no formal treatment guidelines in primary or specialty care for dealing with sleep loss Dinges et al.

The most effective treatment for sleep loss is to sleep longer or take a short nap lasting no more than 2 hours Veasey et al.

Catching up on sleep on the weekends—a popular remedy for sleep loss—does not return individuals to baseline functioning Szymczak et al. In a randomized clinical trial caffeine and modafinil showed similar benefits for performance and alertness Wesensten et al.

Modafinil is the only FDA-approved drug for shift work sleep disorder, although it is not approved for sleep loss. Behavioral approaches developed for insomnia also may be useful for sleep loss, but no formal studies have been undertaken expressly for sleep loss.

Furthermore, there have been no large-scale clinical trials examining the safety and efficacy of modafinil, or other drugs, in children and adolescents. Sleep-disordered breathing refers to a spectrum of disorders that feature breathing pauses during sleep.

The most common disorder is characterized by obstructive apneas and hypopneas White, , where repeated episodes of collapse apneas or partial collapse of the pharyngeal airway occur, usually a result of obstruction by soft tissue in the rear of the throat.

Snoring, which is produced by vibrations of the soft tissues, is a good marker for OSA Netzer, et al. Apneas or hypopneas a reduction without cessation in airflow or effort typically result in abrupt and intermittent reduction in blood oxygen saturation, which leads to sleep arousal, often accompanied by loud snorts or gasps as breathing resumes.

Episodic interruptions of breathing also frequently cause cortical and brainstem arousals, interrupting sleep continuity, reducing sleep time, and causing increased sympathetic nervous system activation.

These broad systemic effects on gas exchange and nervous system activation may lead to a range of systemic effects that affect vascular tone, levels of inflammatory mediators, and hormonal changes. As discussed in the following sections, these in turn may contribute to the development of hypertension, coronary artery disease, congestive heart failure, arrhythmias, stroke, glucose intolerance, and diabetes.

The defining symptom of sleep-disordered breathing is excessive daytime sleepiness. The symptom is likely influenced by sleep fragmentation tied to recurrent arousals that occur in response to breathing pauses.

Other symptoms of fragmented sleep include decreased concentration and mood changes. The diagnosis of OSA requires detection, by polysomnography, of at least five or more apneas or hypopneas per hour of sleep Thorpy, This rate is expressed as an index, the apnea-hypopnea index or respiratory disturbance index , which is the average hourly number of apneas plus hypopneas.

OSA is found in at least 4 percent of men and 2 percent of women in the middle-aged workforce, according to the first major United States population-based study of the condition conducted about 15 years ago Young et al.

Those prevalence figures are based on a cutoff apnea-hypopnea index of 5 or higher, plus a requirement for daytime sleepiness. The prevalence is higher, 9 percent of women and 24 percent of men, with the same apnea-hypopnea index cutoff Box , but without the daytime sleepiness requirement.

In view of the epidemic increase of obesity an important determinant of OSA in recent years, these numbers might underestimate the current prevalence. However, other more recent population-based studies support these prevalence figures Bixler et al.

Definitions Impact Disease Prevalence Estimates. The metric used most commonly to define obstructive sleep apnea and to quantify its severity is the apnea-hypopnea index, derived by identifying and manually counting each respiratory disturbance apnea more OSA prevalence appears to increase with age.

Adults 65 to 90 years of age had a threefold higher prevalence rate than middle-aged adults Ancoli-Israel et al. Underdiagnosis of OSA is common, with between 10 and 20 percent of OSA being diagnosed in adults Young et al.

Less than 1 percent of older adults in primary care are referred for polysomnography Haponik, , although these numbers might have increased in recent years due to increased awareness of the disease. Although OSA can occur in children of any age, it is most common at preschool ages, a time coincident with tonsils and adenoids being largest relative to the underlying airway Jeans et al.

OSA causes chronic elevation in daytime blood pressure Young et al. The strongest evidence for a rise in systemic hypertension comes from several large, well-designed epidemiological studies, both cross-sectional Young et al.

The Wisconsin Sleep Cohort study, a prospective study, tracked adults with sleep-disordered breathing for at least 4 years to determine new onset hypertension and other outcomes. The hypertensive effect was independent of obesity, age, gender, and other confounding factors.

Controlling for obesity is especially important because it is a risk factor for hypertension as well as for OSA. A causal association between OSA and hypertension is supported by evidence of a dose-response relationship; the higher the apnea-hypopnea index, the greater the increase in blood pressure Peppard et al.

Both the Wisconsin Sleep Cohort study and the Sleep Heart Health Study showed dose-response relationships. The Sleep Heart Health Study is a community-based multicenter study of more than 6, middle-aged and older adults whose apnea-hypopnea index was measured by polysomnography.

The likelihood of hypertension was greater at higher apnea-hypopnea index levels. Case-control studies reveal that approximately 30 percent of patients diagnosed with essential hypertension hypertension in which the underlying cause cannot be determined turn out to have sleep apnea Partinen and Hublin, Further, evidence from pediatric studies indicate elevations in systemic blood pressure during both wakefulness and sleep in children with sleep apnea Amin et al.

The causal nature of the relationship between OSA and hypertension is reinforced by randomized controlled clinical trials showing that the most effective treatment for OSA, continuous positive airway pressure CPAP therapy, can reduce blood pressure levels.

The benefit is greatest in patients with severe OSA, determined by objective polysomnography and subjective daytime sleepiness criteria.

The review also concluded that there was a lack of benefit in patients who had no daytime sleepiness Robinson et al. However, each of these studies was relatively small less than individuals , and findings can be considered only tentative.

How does OSA cause sustained hypertension? During the night, the apneas and hypopneas of OSA cause a transient rise in blood pressure 30 mm Hg or more and increased activity of the sympathetic nervous system Figure Over time, the transient changes become more sustained and are detectable during the daytime, including evidence of sympathetic overactivity Narkiewicz and Somers, Studies have found that people with OSA versus those with similar blood pressure, but no OSA have faster heart rates, blunted heart rate variability, and increased blood pressure variability—all of which are markers of heightened cardiovascular risk Caples et al.

The precise pathophysiological steps from transient vascular changes to systemic hypertension are far from clear but may involve oxidative stress, upregulation of vasoactive substances Caples et al. REM sleep recordings for an individual with OSA. NOTE: During even the lowest phase, blood pressure during REM was higher than in the awake state.

Electrooculogram EOG , electroencephalogram EEG , electromyogram EMG , electrocardiogram EKG , sympathetic more Epidemiological studies reveal an association between OSA and cardiovascular disease, including arrhythmias Guilleminault et al. Most case-control studies detecting a relationship with myocardial infarction found adjusted odds ratios of around 4 Young et al.

The large, cross-sectional Sleep Heart Health Study of nearly 6, Shahar et al. The adjusted OR for stroke was 1. A higher probability of stroke associated with OSA is also supported by other studies Bassetti and Aldrich, ; Parra et al.

In the Sleep Heart Health Study, apnea-hypopnea index was deter mined by polysomnography, and adjustments were made for a variety of confounding factors, including hypertension. That the hypertension adjustment did not eliminate the effect suggests that hypertension is not the exclusive means by which OSA may lead to cardiovascular disease.

A limitation of cross-sectional and case-control analyses is that cause and effect cannot be determined: heart disease may have resulted in OSA or vice versa. However, an observational cohort study of 1, individuals, where 68 percent of individuals had OSA apnea-hypopnea index of 5 or higher , showed that OSA syndrome significantly increased the risk of stroke or death from any cause, and the increase is independent of other risk factors, including hypertension Yaggi et al.

Other studies have confirmed the risk of OSA syndrome with stroke or death from any cause Ayas et al. Furthermore, other large prospective studies also have shown an association between snoring—a marker for OSA—and incidence of cardiovascular diseases Jennum et al.

As will be discussed in the next section, OSA is associated with glucose intolerance and diabetes, both of which are independent risk factors for cardiovascular disease. Studies of the benefits of CPAP further support an association between cardiovascular disease and OSA.

The events included myocardial infarction, stroke, and coronary artery bypass surgery. The untreated patients had refused CPAP but were followed regularly.

A second study found an increased mortality rate from cardiovascular disease in individuals who did not maintain CPAP treatment over a 5-year follow-up period Doherty et al. However, the number of new cases of cardiovascular disease was independent of CPAP treatment compliance.

Although observational evidence of this type is not conclusive proof, because it may be subject to confounding by indication and other biases, it still lends weight to the strength of the association. Most studies finding elevated cardiovascular disease risk have been conducted in adults.

Whether or not children with sleep-disordered breathing are at risk for cardiovascular effects is not known. Children with OSA , as noted previously, do experience changes in blood pressure profiles, heart rate variability, and ventricular wall changes as measured by echocardiography Marcus et al.

The paucity of longitudinal data on OSA in children, in whom levels of OSA may vary during growth and development and in whom responses to therapies such as tonsillectomy may be variable Morton et al.

Nonetheless, evidence that as many as 20 to 25 percent of children may have persistent OSA even after tonsillectomy underscores the potential importance of OSA as an early childhood risk factor for later cardiovascular diseases Amin et al.

OSA is associated with impaired glucose tolerance and insulin resistance, according data from several studies Ip et al. Those outcomes were more prevalent in those with the highest apnea-hypopnea index. The study also found a relationship between sleep-related hypoxemia and glucose intolerance, which has implications for understanding mechanisms behind the OSA-glucose intolerance link see below.

The Sleep Heart Health Study, as noted earlier, was a large, cross-sectional, community-based study that used polysomnography to identify OSA. The analyses adjusted for obesity BMI and waist circumference , self-reported sleep duration, and other confounding factors.

The findings suggest that OSA contributes to the onset of diabetes through the development of glucose intolerance and insulin resistance, which are established pathophysiological processes in diabetes Martin et al.

The study found that, after 10 years of follow-up, occasional snoring versus nonsnoring was associated with an elevated risk of new onset diabetes in women, and the risk was even greater for regular snoring Al-Delaimy et al.

Regular or habitual snoring is an indicator of OSA. The relationship between OSA and metabolic changes that may lead to diabetes is reinforced by studies of the benefits of CPAP.

CPAP alleviates glucose intolerance in the short term and long term Brooks et al. In a separate study of people with type 2 diabetes as well as OSA, CPAP improved glycemic control Babu et al.

Recent data also indicate that diabetics with OSA have poorer control of glucose levels, with improvement following treatment of OSA with CPAP Babu et al. The mechanisms by which OSA disrupts glucose metabolism are not established.

Drawing on human studies and animal models, the biochemical cascade begins with intermittent hypoxia and recurrent sleep arousals sleep fragmentation.

These events stimulate the sympathetic nervous system, hypothalamic-pituitary-adrenal axis, and adipocytes Punjabi and Beamer, Their activation, in turn, leads to release of catecholamines, cortisol, and inflammatory cytokines and other vasoactive intermediates, which may mediate the development of glucose intolerance, insulin resistance, and, ultimately, type 2 diabetes.

Because diabetes is also a risk factor for cardiovascular disease, the interrelationships may partly explain why OSA predisposes to cardiovascular disease Punjabi and Beamer, Up to 40 percent of people who are morbidly obese have OSA Vgontzas et al.

This finding may reflect the role of obesity as a well-established risk factor for the development of OSA. It may also reflect obesity as a consequence of OSA, although the evidence is not yet conclusive Grunstein, b.

Patients with newly diagnosed OSA, compared with controls matched for BMI and percent body fat, show recent weight gain Phillips et al. Data from the Wisconsin Sleep Cohort also show that individuals with OSA have reduced levels of physical activity; OSA-related sleepiness may contribute to changes in activity and energy expenditure, and thus contribute to weight gain.

OSA-related hormonal changes may also contribute to obesity. In general, patients with OSA have higher levels of leptin, the appetite-suppressing hormone Phillips et al. However, their morning levels are relatively lower than evening levels Patel et al. Furthermore, obesity also affects the severity of OSA.

Significant weight loss in adolescents who underwent gastric bypass surgery mean, 58 kg was associated with a dramatic reduction of OSA severity Kalra et al. In simplest terms, OSA is caused by narrowing or collapse of the airway as a result of anatomical and physiological abnormalities in pharyngeal structures.

Apnea episodes cause hypoxemia insufficient oxygen in the blood and hypercapnia high concentration of blood carbon dioxide. The episodes also increase the output of the sympathetic nervous system Narkiewicz and Somers, , the effect of which is to restore pharyngeal muscle tone and reopen the airway.

Although increased sympathetic activity is beneficial for restoring normal breathing and oxygen intake over the short term, it has long-term deleterious effects on vascular tone and blood pressure, among other effects Caples et al. These early events—which are mediated by a variety of chemoreceptors in the carotid body and brainstem—trigger pathophysiological changes that occur not only during the obstructive apneas, but also extend into wakeful states during the day.

For example, during daytime wakefulness, people with OSA have higher sympathetic activity Somers, et al. The full pathophysiology of OSA remains somewhat elusive, although research is piecing together the relationships between OSA and a range of the previously described long-term health effects.

The etiology of central sleep apnea, although also not well understood, is hypothesized to result from instability of respiratory control centers White, There are a number of risk factors for OSA , including:. Studies of patients at sleep clinics tend to show an association between sleep apnea and mortality He et al.

The subgroup experienced twice the risk of mortality Lindberg et al. In adults, OSA is most effectively treated with CPAP and weight loss Strollo et al. The problem is that many patients are noncompliant with CPAP see Chapter 6.

Other options, although less effective, include a variety of dental appliances Ferguson and Lowe, or surgery e. In children, the first-line treatment for most cases of OSA is adenotonsillectomy, according to clinical practice guidelines developed by the American Academy of Pediatrics Marcus et al.

Children who are not good candidates for this procedure can benefit from CPAP. Central apnea treatment is tailored to the cause of the ventilatory instability.

Commonly used treatments include oxygen, CPAP, and acetazolamide, a drug that acts as a respiratory stimulant White, Insomnia is the most commonly reported sleep problem Ohayon, It is a highly prevalent disorder that often goes unrecognized and untreated despite its adverse impact on health and quality of life Benca, a see also Chapter 4.

The diagnostic criteria for primary insomnia include:. Insomnia symptoms are remarkably common, affecting at least 10 percent of adults in the United States Ford and Kamerow, ; Ohayon et al. Prevalence is higher among women and older individuals Mellinger et al. Severe insomnia tends to be chronic, with about 85 percent of patients continuing to report the same symptoms and impairment months or years after diagnosis Hohagen et al.

The comorbidity of sleep disorders with psychiatric disorders is covered later in this chapter. The precise causes of insomnia are poorly understood but, in general terms, involve a combination of biological, psychological, and social factors. Insomnia is conceptualized as a state of hyperarousal Perlis et al.

Stress is thought to play a leading role in activating the hypothalamic-pituitary axis and setting the stage for chronic insomnia.

A key study showed that adults with insomnia, compared with normal sleepers, have higher levels, over a hr period, of cortisol and adrenocorticotropic hormone ACTH , which are hormones released by the hypothalamic-pituitary-adrenal axis after stress exposure Vgontzas et al.

The hour pattern of cortisol and ACTH secretion is different, however, from that in individuals who are chronically stressed. Cognitive factors, such as worry, rumination, and fear of sleeplessness, perpetuate the problem through behavioral conditioning.

Other perpetuating factors include light exposure and unstable sleep schedules Partinen and Hublin, Insomnia patients often attribute their difficulty sleeping to an overactive brain. Several lines of evidence, from preclinical to sleep neuroimaging studies in insomnia patients, suggest that there are multiple neural systems arranged hierarchically in the central nervous system that contribute to arousal as well as insomnia complaints.

Disturbances in these systems may differ according to the nature of insomnia. Structures that regulate sleep and wakefulness, for example the brainstem, hypothalamus and basal forebrain, are abnormally overactive during sleep in primary insomnia patients Nofzinger et al.

In addition, limbic and paralimbic structures that regulate basic emotions and instinctual behaviors such as the amygdala, hippocampus, ventromedial prefrontal cortex and anterior cingulate cortex have been shown to be abnormally active during sleep in individuals with primary insomnia and secondary insomnias related to depression Nofzinger et al.

Abnormal activity in neocortical structures that control executive function and are responsible for modulating behavior related to basic arousal and emotions has been observed in individuals with insomnias associated with depression Nofzinger et al.

The two main risk factors of insomnia are older age and female gender Edinger and Means, One large, population-based study found that insomnia was nearly twice as common in women than men, although reporting bias cannot be ruled out as a contributing factor Ford and Kamerow, The reason behind the apparent higher prevalence in women is not understood.

Other risk factors for insomnia include family history of insomnia Dauvilliers et al. Although adolescent age is not viewed a risk factor, insomnia has rarely been studied in this age group.

Insomnia is treatable with a variety of behavioral and pharmacological therapies, which may be used alone or in combination. While the therapies currently available to treat insomnia may provide benefit, the NIH State of the Science Conference on the Manifestations and Management of Chronic Insomnia concluded that more research and randomized clinical trials are needed to further verify their efficacy, particularly for long-term illness management and prevention of complications like depression NIH, Behavioral therapies appear as effective as pharmacological therapies Smith et al.

Behavioral therapies, according to a task force review of 48 clinical trials, benefit about 70 to 80 percent of patients for at least 6 months after completion of treatment Morin et al. The therapies are of several main types Table The major problem with current behavioral therapies is not their efficacy; rather it is lack of clinician awareness of their efficacy and lack of providers sufficiently trained and skilled in their use.

Other problems are their cost and patient adherence Benca, a. The most efficacious pharmacological therapies for insomnia are hypnotic agents of two general types, benzodiazepine or nonbenzodiazepine hypnotics Nowell et al.

Nonbenzodiazepine hypnotics are advantageous because they generally have shorter half-lives, thus producing fewer impairments the next day, but the trade-off is that they may not be as effective at maintaining sleep throughout the night Morin, ; Benca, a.

It is still unclear whether hypnotics lead to dependence. It is suggested that they should not be taken for more than 10 days in a row; however, recent studies suggest that hypnotics do not always lead to dependence Hajak et al.

There have been no large-scale trials examining the safety and efficacy of hypnotics in children and adolescents. Other pharmacological classes used for insomnia include sedating antidepressants, antihistamines, and antipsychotics, but their efficacy and safety for treating insomnia have not been thoroughly studied Walsh et al.

Sleep disturbances are common features of psychiatric disorders. The most frequent types of sleep disturbances are insomnia, excessive daytime sleepiness hypersomnia , and parasomnia. Sleep disturbances are so commonly seen as symptoms of certain psychiatric disorders that they are listed as diagnostic criteria under DSM-IV APA, For example, insomnia is a symptom used with others to diagnose major depression.

The comorbidity, or coexistence, of a full-blown sleep disorder particularly insomnia and hypersomnia with a psychiatric disorder is also common.

Forty percent of those diagnosed with insomnia, in a population-based study, also have a psychiatric disorder Ford and Kamerow, Among those diagnosed with hypersomnia, the prevalence of a psychiatric disorder is somewhat higher— The reasons behind the comorbidity of sleep and psychiatric disorders are not well understood.

Comorbidity might be due to one disorder being a risk factor or cause of the other; they might both be manifestations of the same or overlapping physiological disturbance; one might be a consequence of the other. In some cases, the sleep disturbance can be both cause and consequence.

In generalized anxiety disorder, for example, the symptoms of fatigue and irritability used to diagnose it are often the result of a sleep disturbance, which itself is also a diagnostic symptom. Adolescents with major depressive disorders report higher rates of sleep problems and, conversely, those with sleep difficulties report increased negative mood or mood regulation Ryan et al.

In addition, sleep-onset abnormalities during adolescence have been associated with an increased risk of depression in later life Rao et al. The best studied and most prevalent comorbidity is insomnia with major depression.

Insomnia as a symptom of depression is highly common. On the basis of longitudinal studies, insomnia is now established as a risk factor for major depression.

Not all people with insomnia have a depression diagnosis; however, studies have found that 15 to 20 percent of people diagnosed with insomnia have major depression Ford and Kamerow, ; Breslau et al.

Depressed individuals have certain abnormalities detected by polysomnography. One is shorter rapid eye movement REM latency a shorter period of time elapsing from onset of sleep to onset of REM sleep , an effect that persists even after treatment for depression.

Other abnormalities include shortened initial REM period, increased REM density, and slow-wave deficits Benca, a. Shorter REM latency and slow-wave sleep SWS deficits tend to run in families; these abnormalities are also found in first-degree relatives of people with major depression, but who are unaffected by depression Giles et al.

A variety of polysomnographic abnormalities have been found with other psychiatric disorders Benca, a. The etiological basis for the comorbidity of sleep disorders and psychiatric disorders is not well understood.

Most potential mechanisms for sleep changes in psychiatric disorders deal specifically with insomnia and depression. Possible mechanisms include neurotransmitter imbalance cholinergic-aminergic imbalance , circadian phase advance, and hypothalamic-pituitary-adrenal axis dysregulation Benca, a.

Recent evidence implicating regions of the frontal lobe has emerged from imaging studies using positron emission tomography.

As they progress from waking to non- REM NREM sleep, depressed subjects have smaller decreases in relative metabolism in regions of the frontal, parietal, and temporal cortex when compared to individuals who are healthy Nofzinger et al. Normally, the transition from waking to NREM sleep is associated with decreases in these frontal lobe regions.

What appears to occur with depression is that the decrease is less pronounced. Because the amygdala also plays a role in sleep regulation Jones, , this finding suggests that sleep and mood disorders may be manifestations of dysregulation in overlapping neurocircuits.

The authors hypothesize that increased metabolism in emotional pathways with depression may increase emotional arousal and thereby adversely affect sleep Nofzinger et al.

A major problem is underdiagnosis and undertreatment of one or both of the comorbid disorders. One of the disorders may be missed or may be mistakenly dismissed as a condition that will recede once the other is treated. In the case of depression, for example, sleep abnormalities may continue once the depression episode has remitted Fava, If untreated, residual insomnia is a risk factor for depression recurrence Reynolds et al.

Further, because sleep and psychiatric disorders, by themselves, are disabling, the treatment of the comorbidity may reduce needless disability. Insomnia , for example, worsens outcomes in depression, schizophrenia, and alcohol dependence.

Another concern is that medication for one disorder might exacerbate the other e. The choice of medica tion for psychiatric disorder or vice versa should be influenced by the nature of the sleep complaint e. As mentioned above insomnia is associated with depression, acting as both a risk factor and a manifestation Ford and Kamerow, ; Livingston et al.

Several studies done were longitudinal in design, including one that tracked more than 1, male physicians for 40 years Chang et al.

Another study, which followed 1, young adults at a health maintenance organization for 3. This figure is based on 16 percent of the sample who developed depression with a history of insomnia at baseline, as compared with 4.

Insomnia is also a predictor of acute suicide among patients with mood disorders Fawcett et al. Incidence of psychiatric disorders during 3. SOURCE: Breslau et al. The striking association between insomnia and depression in so many studies suggests that insomnia is also an early marker for the onset of depression, and the two may be linked by a common pathophysiology.

One hypothesis is that common pathways are the amygdala and other limbic structures of the brain Nofzinger et al. Another hypothesis is that chronic insomnia increases activity of the hypothalamic-pituitary-adrenal axis, which in turn contributes to depression Perlis et al.

The close association of insomnia and depression also raises the tantalizing possibility that treating insomnia may prevent some cases of depression Riemann and Voderholzer, , but limited data are available.

The biological basis for the relationship between insomnia and new onset psychiatric disorders other than depression is also not known. Narcolepsy and idiopathic hypersomnia are characterized by a clinically significant complaint of excessive daytime sleepiness that is neither explained by a circadian sleep disorder, sleep-disordered breathing, or sleep deprivation, nor is it caused by a medical condition disturbing sleep AASM, The diagnosis of narcolepsy and hypersomnia is based principally on the Multiple Sleep Latency Test MSLT , which objectively quantifies daytime sleepiness Box Carskadon et al.

Sleep logs or actigraphy a movement detector coupled with software that uses movement patterns to provide estimate sleep and wake times can also be used to exclude chronic sleep deprivation as a diagnosis prior to the MSLT.

In many cases narcolepsy arises during the mid to late teenage years; however, frequently initial diagnosis is not correct, resulting in delays in diagnosis of 15 to 25 years after the onset of symptoms Broughton et al.

Onset of narcolepsy can also have a negative impact on school performance see Chapter 4. Narcolepsy is associated with a number of symptoms Anic-Labat et al.

Clinical Laboratory Findings in Narcolepsy and Hypersomnia. The Multiple Sleep Latency Test MSLT objectively quantifies daytime sleepiness.

It consists of five 20 minute daytime naps at 2-hour intervals. The amount of time it takes to fall asleep sleep more Narcolepsy can be diagnosed clinically, by using the MSLT , or by measuring cerebrospinal fluid CSF hypocretin-1 Box Idiopathic hypersomnia is classically separated into two subtypes.

The first, idiopathic hypersomnia with prolonged sleep time, is a rare disorder and is characterized by the following:. The second subtype of idiopathic hypersomnia, idiopathic hypersomnia without long sleep time, is characterized by a complaint of excessive daytime sleepiness and a short mean sleep latency on the MSLT.

In most sleep disorders clinics with experience in this area, approximately one-third of hypersomnia cases are diagnosed with this condition Aldrich, The prevalence is estimated to be around 0. In contrast, the prevalence of idiopathic hypersomnia without prolonged sleep time may be more substantial, as most patients are likely not diagnosed Arand et al.

Recurrent hypersomnia is periodic either in synchrony with menstruation menstruation-linked periodic hypersomnia or without any association and mostly in males with Klein-Levin syndrome Billiard and Cadilhac, ; Arnulf et al. Klein-Levin syndrome is characterized by recurrent episodes of dramatic hypersomnia lasting from 2 days to several weeks.

These episodes are associated with behavioral and cognitive abnormalities, binge eating or hypersexuality, and alternate with long asymptomatic periods that last months or years Arnulf et al. Narcolepsy and hypersomnia can affect children, adolescents, adults, and older persons.

In most cases these disorders begin in adolescence. The prevalence of narcolepsy with definite cataplexy has been documented in adults by numerous population-based studies and occurs in 0. In contrast, very little is known about the prevalence of narcolepsy without cataplexy.

Recent studies using the MSLT indicate that approximately 3. Secondary cases of narcolepsy or hypersomnia are also common, but the overall prevalence is not known Table International Classification of Sleep Disorders: Definitions, Prevalence, and Pathophysiology of Narcolepsy and Hypersomnias.

Similar to other sleep disorders, little is known about the pathophysiology and risk factors for narcolepsy and hypersomnia. Most of the knowledge in this area pertains to narcolepsy with cataplexy, which affects males and females equally. Symptoms usually arise during adolescence. Approximately 70, hypothalamic neurons that are responsible for producing the neuropeptide hypocretin orexin are lost in individuals with narcolepsy with cataplexy Thannickal et al.

Hypocretin is an excitatory neuropeptide that regulates the activity of other sleep regulatory networks. Consequently, in some cases low levels of hypocretin-1 in the CSF , may be used to diagnose narcolepsy Kanbayashi et al.

Less is known regarding the pathophysiology of narcolepsy without cataplexy. The etiology is likely heterogeneous. An unknown portion may be caused by partial or complete hypocretin deficiency Kanbayashi et al.

However, it has been hypothesized that some individuals with partial cell loss may have normal CSF hypocretin-1 Mignot et al. The pathophysiology of idiopathic hypersomnia is unknown. When the disorder is associated with prolonged sleep time, it typically starts during adolescence and is lifelong.

It is essential to exclude secondary causes, such as head trauma or hypersomnia owing to depression Roth, ; Billiard and Dauvilliers, Some cases with prolonged sleep times have been reported to be familial, suggesting a genetic origin.

Even less is known about idiopathic hypersomnia with normal sleep time. This condition is more variable and symptomatically defined. The cause of Kleine-Levin syndrome is unknown Arnulf et al. Treatment for these conditions is symptomatically based.

Even in the case of narcolepsy in which the disorder is caused by hypocretin deficiency, current treatment does not aim at improving the defective neurotransmission Mignot et al.

Behavioral measures, such as napping, support groups, and work arrangements are helpful but rarely sufficient.

In most cases, pharmacological treatment is needed Nishino and Mignot, ; Lammers and Overeem, However, as with other pharmaceuticals designed to treat sleep problems, large-scale clinical trails have not examined the efficacy and safety of drugs to treat narcolepsy in children and adolescents.

In narcolepsy with cataplexy, pharmacological treatment for daytime sleepiness involves modafinil or amphetamine-like stimulants, which likely act through increasing dopamine transmission.

Cataplexy and abnormal REM sleep symptoms, sleep paralysis and hallucinations, are typically treated with tricyclic antidepressants or serotonin and norepinephrine reuptake inhibitors. Adrenergic reuptake inhibition is believed to be the primary mode of action.

Sodium oxybate, or gamma hydroxybutyric acid, is also used at night to consolidate disturbed nocturnal sleep. This treatment is also effective on cataplexy and other symptoms.

The treatment of narcolepsy without cataplexy and idiopathic hypersomnia uses similar compounds, most notably modafinil and amphetamine-like stimulants Billiard and Dauvilliers, Treatments, with the possible exception of lithium, of periodic hypersomnia and Kleine-Levin syndrome type are typically ineffective Arnulf et al.

Parasomnias are unpleasant or undesirable behaviors or experiences that occur during entry into sleep, during sleep, or during arousals from sleep AASM, They are categorized as primary parasomnias, which predominantly occur during the sleep state, and secondary parasomnias, which are complications associated with disorders of organ systems that occur during sleep.

Primary parasomnias can further be classified depending on which sleep state they originate in, REM sleep, NREM , or others that can occur during either state Table Parasomnias typically manifest themselves during transition periods from one state of sleep to another, during which time the brain activity is reorganizing Mahowald and Schenck, Activities associated with parasomnias are characterized by being potentially violent or injurious, disruptive to other household members, resulting in excessive daytime sleepiness, or associated with medical, psychiatric, or neurological conditions Mahowald and Ettinger, Disorders of arousal are the most common type of parasomnia, occurring in as much as 4 percent of the adult population Ohayon et al.

Typically the arousals occur during the first 60 to 90 minutes of sleep and do not cause full awakenings, but rather partial arousal from deep NREM sleep. Disorders of arousal manifest in a variety of ways, from barely audible mumbling, disoriented sleepwalking, to frantic bouts of shrieking and flailing of limbs Wills and Garcia, Individuals who experience confusional arousals exhibit confused mental and behavioral activity following arousals from sleep.

They are often disoriented in time and space, display slow speech, and blunted answers to questions AASM, Episodes of resistive and even violent behavior can last several minutes to hours.

Confusional arousals are more than three to four times more prevalent in children compared to individuals 15 years or older around 3 percent Ohayon et al.

Sleepwalking is characterized by a complex series of behaviors that culminate in walking around with an altered state of consciousness and impaired judgment AASM, Individuals who are sleepwalking commonly perform routine and nonroutine behaviors at inappropriate times and have difficulty recalling episodic events.

Like confusional arousals, the prevalence of sleepwalking is higher in children than adults AASM, There appears to be a genetic predisposition for sleepwalking. Children who have both parents affected by sleepwalking are 38 percent more likely to also be affected Klackenberg, ; Hublin et al.

Sleep terrors are characterized by arousal from SWS accompanied by a cry or piercing scream, in addition to autonomic nervous system and behavioral manifestations of intense fear AASM, Individuals with sleep terrors are typically hard to arouse from sleep and, when they are awoken, are confused and disoriented.

There does not appear to be a significant gender or age difference in prevalence or incidence of sleep terrors AASM, REM sleep behavior disorder is characterized by a complex set of behaviors that occur during REM sleep, including mild to harmful body movements associated with dreams and nightmares AASM, The overall prevalence in the general population is estimated to be less than half a percent, slightly higher in older persons AASM, , and affecting men more frequently than women.

REM sleep behavior disorder is frequently associated with neurological disorders and it has been suggested that it could be an early sign of neurodegeneration Olson et al. There are a number of effective pharmacological treatments, including a long-acting benzodiazepine Schenck and Mahowald, , clonazepam Schenck et al.

Nightmare disorder is characterized by recurrent disturbances of dreaming that are disturbing mental experiences that seem real and sometimes cause the individual to wake up.

If awoken, individuals commonly have difficulty returning to sleep. Nightmares often occur during the second half of a normal period of sleep.

Dream content involves a distressing theme, typically imminent physical danger. During nightmares, individuals experience increased heart and respiration rates Fisher et al. Nightmares commonly affect children and adolescents and decrease in frequency and intensity as an individual grows older AASM, Drugs and alcohol can trigger nightmares.

Prevalence rates are also higher in individuals suffering from acute stress disorder and posttraumatic stress disorder. Individuals suffering from dementia commonly experience sleep abnormalities.

Typically, sleep is more fragmented, leading to more awakenings and consequently less time asleep, and REM may be decreased Petit et al. These sleep impairments usually worsen as the disease progresses.

Approximately one-quarter of these individuals have sleep disturbances Tractenberg et al. As a result of an increase in duration and number of awakenings, individuals spend an increased percentage of time in stage 1 sleep and a reduced percentage in stage 2 and SWS Prinz et al. Associations with sleep disturbance and other behavioral symptoms have been identified, including aggressiveness Moran et al.

However, the pathophysiology of this association is not known. Treatment options for demented individuals who suffer sleep disorders are typically the same as those received by individuals who do not have dementia. The approach is to address the sleep disorder based on its symptoms while managing and treating the underlying medical or psychiatric disorder Petit et al.

It is characterized by trouble initiating walking and other movements, muscle tremor, a slow gait, and reduced facial expressions. During the day, many Parkinson patients have excessive sleepiness. Sleep disturbances typically increase with disease progression. Individuals suffer from increased sleep latency and frequent awakenings, spending as much as 30 to 40 percent of the night awake Kales et al.

This causes reduced time spent in stages 3 and 4 and REM sleep and increased duration in stages 1 and 2 Kales et al. Sleep patterns are affected by abnormalities caused by neurodegeneration in regions of the brain that are involved in regulating the sleep-wake cycle.

Dopaminergic neurons in the substantia nigra are dramatically reduced in number, as are noradrenerics neurons in the locus coeruleus Jellinger, and cholinergic neurons in the pedunculopontine nucleus Zweig et al.

Braak and colleagues examined a large series of autopsy brains. The ability to ameliorate the symptoms of REM sleep behavioral disorder with dopaminergic agonist drugs suggests that it may be an early sign of damage to the dopaminergic system Trampus et al. When used in low doses, these medications can promote sleep, but high doses may cause increased nocturnal wakefulness, decreased SWS , and decreased sleep continuity Leeman et al.

In contrast, excessive daytime sleepiness, including sleep attacks, has also been described in association with dopamine agonists Paus et al. All may potentially affect sleep Chrisp et al.

Epilepsy refers to a group of various disorders characterized by abnormal electrical activity in the brain that manifests itself in individuals as a loss of or impaired consciousness and abnormal movements and behaviors. Sleep, sleep deprivation, and seizure activity are tightly intertwined.

It is estimated that sleep-related epilepsy may affect as many as 10 percent or more of epileptic individuals AASM, Sixty percent of individuals who suffer partial complex localization related seizures— Similarly, sleep and sleep deprivation increase the incidence of seizure activity.

Sleep-related epilepsy normally presents with at least two of the following features: arousals, abrupt awakenings from sleep, generalized tonic-clonic movements of the limbs, focal limb movement, facial twitching, urinary incontinence, apnea, tongue biting, and postictal confusion and lethargy AASM, These features cause sleep fragmentation and daytime fatigue.

There are a number of common epileptic syndromes that manifest solely or predominately during the night, including nocturnal frontal lobe epilepsy, benign epilepsy of childhood with centrotemporal spikes, early-onset or late-onset childhood occipital epilepsy, juvenile myoclonic epilepsy, and continuous spike waves during non- REM sleep.

Nocturnal frontal lobe epilepsy is characterized by severe sleep disruption, injuries caused by involuntary movements, and occasional daytime seizures. Juvenile myoclonic epilepsy is characterized by synchronous involuntary muscle contractions that often occur during awakening.

Continuous spike waves during non-REM sleep epilepsy are commonly associated with neurocognitive impairment and sometimes with impairment of muscle activity and control. Risk factors for sleep-related epilepsy include stress, sleep deprivation, other sleep disorders, and irregular sleep-wake rhythms.

The etiologies for nocturnal seizures are not clearly understood. Genetic factors are likely important; however, as of yet no pathogenic markers have been associated with sleep-related epilepsy. There are specific patterns of rhythmic activity among neurons within specific regions of the brain—the hypothalamus and brainstem—that regulate sleep and arousal.

Association of specific neuronal activity between these different regions is important for regulating sleep, while bursts of disassociated neuronal activity may contribute to nocturnal seizures Tassinari et al.

Treatments for seizures caused by sleep-related epileptic syndromes are typically similar to those of other seizure disorders Dreifuss and Porter, Individuals with epilepsy are susceptible to nocturnal sleep disturbance and daytime sleepiness associated with commonly used medications.

However, daytime hypersomnolence is not always treatable with antiepileptic drugs Palm et al. In particular, phenobarbital, a mainstay of treatment for many years, causes daytime sedation in a dose depen dent manner Brodie and Dichter, Daytime sedation is also observed with other antiepileptic agents including carbamazepine, alproate, phenytoin, and primidone.

Some of the newer medication such as gabapentin, lamotrigine, bigabatrin, and zonisamide are often better tolerated Salinsky et al.

In addition to daytime sedation, these drugs also cause increased nocturnal sleep time. Vagal nerve stimulation, however, has been reported to improve daytime alertness Rizzo et al.

Stroke results in a sudden loss of consciousness, sensation, and voluntary movement caused by disruption of blood flow—and therefore oxygen supply—to the brain. Insomnia is a common complication of stroke that may result from medication, inactivity, stress, depression, and brain damage.

At some point, many adults have short-term insomnia. This can last for days or weeks. Short-term insomnia is usually due to stress or a distressing event.

But some people have long-term insomnia, also called chronic insomnia. This lasts for three months or more. Insomnia may be the main problem, or it may be related to other medical conditions or medicines.

You do not have to put up with sleepless nights. Simple changes in your daily habits often can help. If insomnia makes it hard for you to do daily activities, see your doctor or another primary care professional.

Your doctor will search for the cause of your sleep problem and help treat it. If it's thought that you could have a sleep disorder, your doctor might suggest going to a sleep center for special testing. There is a problem with information submitted for this request.

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Long-term insomnia is usually due to stress, life events or habits that disrupt sleep. While treating the cause of your sleep problem may stop your insomnia, sometimes it can last for years. Sleep problems may be a concern for children and teenagers too.

But some children and teens simply have trouble getting to sleep or resist a regular bedtime because their internal clocks are more delayed. They want to go to bed later and sleep later in the morning. Sleep is as important to your health as a healthy diet and regular physical activity.

Whatever is keeping you from sleeping, insomnia can affect you mentally and physically. People with insomnia report a lower quality of life compared with people who sleep well. Insomnia care at Mayo Clinic.

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This content does not have an English version. This content does not have an Arabic version. Overview Insomnia is a common sleep disorder that can make it hard to fall asleep or stay asleep.

Request an appointment. Thank you for subscribing! Sorry something went wrong with your subscription Please, try again in a couple of minutes Retry. More Information Insomnia care at Mayo Clinic Lack of sleep: Can it make you sick?

By Mayo Clinic Staff. Show references Allscripts EPSi. Mayo Clinic, Rochester, Minn. What is insomnia? National Heart, Lung, and Blood Institute.

Accessed March 10, Personality disorders. In: Diagnostic and Statistical Manual of Mental Disorders DSMTR. American Psychiatric Association; ; doi Sleep disorders. National Alliance on Mental Illness.

Approach to the patient with a sleep or wakefulness disorder. Merck Manual Professional Version. Sutton EL. Annals of Internal Medicine. A good night's sleep. National Institute on Aging.

In: Ham's Primary Care Geriatrics. Accessed March 23, Bonnet MH, et al. Clinical features and diagnosis of insomnia. Risk factors, comorbidities, and consequences of insomnia in adults. Insomnia and other sleep disorders in older adults. Psychiatric Clinics of North America. Natural Medicines.

About AASM accredited facilities. American Academy of Sleep Medicine.