Clinical manifestations

Presentation and course

	• Persons affected by sleep deprivation often report daytime sleepiness that interferes with their activities and functioning.
	• Other symptoms commonly associated with sleep deprivation include lack of energy, muscle weakness, muscle pain, gastrointestinal disturbances, headache, and difficulties with concentration and attention.
	• Various functions of the body are affected, and sleep deprivation has an impact on neurologic disorders.

Insufficient sleep syndrome typically presents in younger to middle-aged adults (25 to 34 years old), with prevalence decreasing with age. It is more common in individuals who work the night shift or more than 40 hours per week. It has a slight female predominance. Patients often report daytime sleepiness that interferes with their activities and functioning. For example, patients with insufficient sleep may inadvertently fall asleep during sedentary activities, such as meetings, reading, watching television or movies, or while driving. Insufficient sleep is associated with an increased risk for motor vehicle accidents (27).

The sleep history suggests insufficient sleep by the disparity in reported amount of sleep on weekends relative to weekdays, often 2 hours or more. The excessive daytime sleepiness may become more pronounced in the late afternoon and early evening. Sleepiness usually improves during vacations, but patients do not recognize that they have also increased their time in bed. They may have no history of alcohol or illicit drug abuse; however, some patients consume large amounts of caffeine or resort to the use of over-the-counter stimulants to combat sleepiness. One half of patients in one series had been previously prescribed stimulants.

Symptoms commonly associated with excessive daytime sleepiness of any cause are also seen in insufficient sleep syndrome, including lack of energy, fatigue, muscle weakness, muscle pain, gastrointestinal disturbances, dry mouth, headache, blurred vision, difficulties with concentration and attention, reduced motivation, irritability, and dysphoria. Any of these symptoms may become the primary focus of the patient and obscure the excessive daytime sleepiness. Importantly, functional and cognitive impairment due to chronic sleep deprivation is often unrecognized by the sufferer.

Prognosis and complications

Complications of insufficient sleep may involve all systems of the body, and important sequelae are listed in Table 1. Recovery from short-term sleep deprivation may occur by restoration of adequate sleep, but long-term sleep deprivation may result in permanent sequelae.

Table 1. Effects of Insufficient Sleep

	• Daytime sleepiness • Anxiety and depression • Effects on functions of the brain
		-- Cognitive impairment -- Memory disorders
	• Effects on structure of the brain (sleep deprivation studies on rats)
		-- Reduction of cells in the dentate gyrus of the hippocampus -- Structural changes in the cortical neurons -- Degeneration of locus ceruleus neurons
	• Effects on electrical activity of the brain
		-- Activation of interictal EEG and precipitation of seizures in epileptic subjects (46)
	• Effects on body weight
		-- Weight gain during insufficient sleep reverses when normal sleep is resumed -- Decrease of appetite-suppressing hormone leptin whereas levels of ghrelin, a hunger promoter, increase spurring a greater desire for food
	• Glucose metabolism
		-- Glucose tolerance test shows a prediabetic state in otherwise normal persons -- Increased insulin resistance in diabetes
	• Cardiovascular system
		-- Atherosclerosis -- Coronary heart disease -- Increased risk of hypertension
	• Reproductive system
		-- Impairment of sperm health
	• Genes linked with immune and inflammatory processes: up- or downregulation • Effects related to disruption of circadian rhythms and insufficient sleep --Increased risk of cancer
	• Disturbance of thermal homeostasis -- Susceptibility to cold- and heat-related illnesses

The sleepiness associated with insufficient sleep syndrome persists and may get worse without a change in sleep habits. The excessive sleepiness places the subject at increased risk of automobile and industrial accidents, declining job performance, and disrupted social relationships. Sleep deprivation in physicians adversely affects patient care. Impairment of driving abilities due to sleep deprivation is comparable to driving when intoxicated with alcohol and is further exacerbated with concurrent alcohol use. There also are risks associated with excessive caffeine intake or stimulant use that often occurs in patients with insufficient sleep syndrome. Other complications of sleep deprivation include headaches, impaired cognitive functions including language tasks, serial subtraction, memory, attention, and decision making.

Many adolescents are sleep deprived and cannot obtain the required 9 hours of nocturnal sleep because of their circadian tendency to have a late bedtime and an early start time in school. In adolescents, inadequate sleep impairs attention as well as concentration and has a negative impact on academic performance. One study supports the notion that sleep loss worsens mood states in healthy adolescents, with females having heightened vulnerability (49). Findings from the National Sleep Foundation’s Sleep in America poll from 2007 revealed that tiredness is an epidemic in adolescents. Twenty-eight percent of high school students admitted to falling asleep at least once a week while in school, and 10% of high school seniors admitted that they have nodded off while driving over a 1-year period (37). In children, there is also an association between short sleep duration and being overweight (19).

Anxiety and depression. Chronic insufficient sleep usually results in a more negative mood, with reduced optimism and sociability. Sleep is a potential biomarker for suicidal behavior. A systematic review of literature has revealed a significant association between sleep disturbances and risk of suicide with significant contribution from sleep deprivation-induced neurocognitive deficits, emotional dysregulation, and negative feelings, among other factors (50).

Chronic sleep deprivation is associated with elevated cortisol and decreased testosterone levels. Testosterone is known to enhance the function of the gamma-aminobutyric acid and serotonin systems in the brain. This reduced function provides one possible causal link between 2 of the most commonly associated psychiatric disorders, depression, and anxiety.

Impairment of brain function. The effects of sleep deprivation on neurocognitive abilities are complex and have been the subject of many studies over the past decade. There is an increasing body of evidence that cognitive complications of sleep deprivation are numerous and are a result of negative effects on the prefrontal cortex and posterior parietal systems. In addition to prefrontal cortex dysfunction, various brain regions involved in verbal working memory have been evaluated and demonstrated vulnerability in the context of sleep deprivation.

Structural changes in human hippocampal subfields resulting from sleep deprivation play a role in determining vulnerability to impairment of memory and are also associated with the quality of NREM slow-wave oscillations during recovery sleep; they also play a role in determining the extent of memory restoration (47). These findings may serve as a predictive biomarker of susceptibility to memory impairment and recovery from sleep deprivation in professions where memory function is critical and insufficient sleep is prevalent. A double-blind, placebo-controlled randomized study to determine the impact of sleep restriction (reduction of 1 hour of habitual sleep duration) on cognitive performance showed impairment of a test of working memory but no effect on tests of sustained attention or decision making (48). Sleep deprivation causes impairment of cognitive flexibility, ie, feedback is less effective in driving behavior modification under changing circumstances (22).

Sleep deprivation may affect the performance in professions requiring intact cognitive function. There has been considerable concern about the performance of overworked and sleep-deprived residents in university hospitals. A study has shown that sleep-deprived surgeons' technical skills are between 11.9% and 32% negatively impacted in a standardized simulated environment, which is likely to have clinical implications for patient safety (54).

Structural and biochemical changes in the brain. Several experimental studies in rats have shown that sleep deprivation causes structural changes in the central nervous system. Sleep-deprived basal forebrain—one of the brain’s main wakefulness centers—experiences an increased release of nitric oxide leading to a buildup of adenosine, a nucleoside that can also affect neural function. Sleep deprivation increases heat shock protein expression in mice. In experiments on mice, extended wakefulness results in reduced sirtuin type 3 (SirT3) activity and, ultimately, degeneration of locus ceruleus neurons (55). Prolonged wakefulness is a metabolic stressor to locus ceruleus neurons leading to failure of adaptive mitochondrial metabolic responses mediated by SirT3, which coordinates mitochondrial energy production and redox homeostasis.

Animal studies have indicated that sleep is essential for maintenance of integrity of cell membranes and myelin in the brain, which are susceptible to sleep deprivation. A diffusion tensor imaging study of normal human volunteers showed that sleep deprivation was associated with widespread decreases in fractional anisotropy that indicate reductions in axial diffusivity, mainly including bilateral frontotemporal and parieto-occipital white matter, the corpus callosum, the thalamus, and the brain stem (15). The findings of this study are consistent with the view that microstructural changes occur in the white matter of the adult human brain over hours to days of sleep deprivation. Permeability of the blood-brain barrier is increased in rats subjected to sleep loss of long duration and is restored following sleep recovery. An ultrastructural study in rats has shown that chronic sleep loss disrupts interendothelial junctions that leads to blood-brain barrier hyperpermeability in the hippocampus (23). The authors of the study suggest that this is because expression of claudin-5, which regulates blood-brain barrier permeability by modifying brain microvascular endothelial cells, is decreased after chronic sleep loss as compared to intact animals.

Diffusion tensor imaging has been applied to the study of diseases characterized by cognitive instability, which is amplified by sleep deprivation and measured by number of lapses on the psychomotor vigilance test (56). There was a considerable inter-individual variation of cognitive instability in response to sleep deprivation, which was associated with differences in white matter integrity.

Cardiovascular effects. Research in the cardiac effects of sleep deprivation has shown that both acute total and short-term partial sleep deprivation results in elevated high-sensitivity C-reactive protein concentrations, a biomarker of inflammation that has been shown to be predictive of cardiovascular morbidity. A review of clinical trials has shown that sleep deprivation can induce autonomic nervous dysfunction, hypertension, arrhythmia, oxidative stress, endothelial dysfunction, inflammation, and metabolic disorder in coronary heart disease patients (45).

Aircraft noise causes endothelial dysfunction, oxidative stress, and inflammation, which are known risk factors for cardiovascular disease. The underlying mechanism was investigated in NADPH oxidase (Nox2) knockout mice subjected to different aircraft noise protocols (28). Results indicate that aircraft noise increases vascular and cerebral oxidative stress via Nox2 and that sleep deprivation or fragmentation caused by noise triggers vascular dysfunction. In patients with established coronary artery disease, nighttime aircraft noise increases oxidative stress and inflammation biomarkers in serum. These findings form the basis of recommendations for preventive measures to reduce nighttime aircraft noise.

Results of a study of circadian rhythm disorder in women showed a rise in blood pressure, decreased muscle mass, and melatonin production, as well as increased visceral fat levels and insulin resistance, which are risk factors for hypertension (34).

Effects on the reproductive system. Results of a randomized study on Chinese men showed that sleep deprivation with late bedtime was associated with impaired sperm health in the study cohort, partly through increase of antisperm antibody production in the semen (31).

Metabolic syndrome. Several epidemiologic studies show an association between sleep duration of less than 6 hours nightly and obesity and diabetes. Sleep restriction decreases glucose tolerance and insulin sensitivity without adequate compensation in beta cell function. Sleep deprivation has also been shown to reduce leptin and increase ghrelin levels, hormones that increase hunger and appetite (26). Even a relatively brief period of mild sleep deprivation (one and half hours of sleep loss per night over 3 weeks) can lead to changes in insulin sensitivity and body weight (44). Furthermore, sleep deprivation may alter the content of the foods we choose to eat. In a study, 11 subjects increased their consumption of calories from snacks, choosing foods with higher carbohydrate content when sleep deprived to 5.5 hours nightly, as compared to when sleeping 8.5 hours per night (38). A small study looking at cerebral functional MRI showed that subjects who were sleep deprived to 5 hours had a greater increase in brain activity in areas associated with reward when exposed to food stimuli as compared to when they were well rested (52).

Immune system, inflammation, and infection. Systemic infections have been induced in animal models by sleep deprivation. The impact of sleep deprivation on the immune response in humans has been shown to have important consequences. Sleep deprivation has been shown to decrease antibody production following influenza vaccination. In a small study, sleep deprivation dampened the normal circadian T-cell function and regulation, which occurs over a 24-hour period (07). A prospective observational study involving over 50,000 nurses showed that sleeping less than 5 hours per night was associated with a 1.39 relative risk of developing pneumonia (41).

Genetic factors in susceptibility to effects of sleep deprivation. Although sleep duration can be influenced by environmental factors and chronotype, human familial sleep disorders indicate that there is a strong genetic modulation of sleep. Studies on identical and fraternal twins have shown that resiliency and vulnerability to sleep loss are highly heritable (29). There is an ongoing search for genes related to vulnerability phenotype, but none has been identified that can explain the different responses to sleep deprivation. Individual differences in energy balance responses to sleep restriction indicate these responses are phenotypic, with behavioral, physiological, and genetic differences underlying these responses. High-density genome-wide association studies for sleep duration in European populations have identified an intronic variant in the ABCC9 gene that explains approximately 5% of the variation in sleep duration (01). ABCC9 encodes an ATP-sensitive potassium channel subunit (SUR2), which serves as a sensor of intracellular energy metabolism.

Identification of biomarkers, including genetic polymorphisms related to orexin signaling, are important for predicting an individual’s vulnerability to overeating and gaining weight when sleep deprived as they will be an important factor in the management of these problems (51).

Sleep deprivation and the epigenome. Although neuronal effects of sleep deprivation start at the DNA and RNA level resulting in dysregulation of cognitive functions, the epigenome plays an important role in regulating gene expression in this context (16). One example is that sleep deprivation disrupts the cyclic adenosine 3′,5′-monophosphate (cAMP) pathway and CREB (cAMP response element-binding) protein, which mediates histone deacetylase inhibitors, a common epigenetic mechanism.

Effect of insufficient sleep on circadian rhythms. Sleep homeostasis, circadian rhythmicity, and metabolism are interrelated. In mice, sleep restriction leads to approximately an 80% reduction in circadian transcripts in the brain and severe disruption of the liver transcriptome, whereas in humans, sleep restriction leads to a 1.9% reduction in circadian transcripts in whole blood (03). Despite significant reduction in the circadian regulation of transcription in peripheral tissues, rhythms within the suprachiasmatic nucleus are not disrupted. Molecular pathways associated with these disruptions point to molecular mechanisms underlying established adverse effects of sleep deprivation.

Increased risk of cancer due to disruption of circadian rhythms and insufficient sleep. Epidemiologic studies suggest increased risk for breast cancer in night- and rotating-shift female workers, which may be due to several interconnected mechanisms resulting from shift work, such as suppression of melatonin by exposure to light at night, impairment of the immune system due to sleep-deprivation, and metabolic changes with generation of proinflammatory reactive oxygen species (20). This topic, however, is controversial. A large prospective study in Sweden found no association between insufficient sleep and risk of prostate cancer (33).

Disturbance of thermal homeostasis. Short-term, ie, less than or equal to 4 nights, sleep deprivation can disturb thermal homeostasis, which affects autonomic and behavioral thermoeffectors during acute exposure to low and high ambient temperatures (25). This may be a predisposing factor for the development of thermal injuries.

Sleep deprivation and neurologic disorders. The MedLink article on insomnia describes sleep disorders that occur in various neurologic disorders. The impact of sleep deprivation in several neurologic disorders has been reviewed (06). Important findings are summarized in a Table 2.

Table 2: Effect of Sleep Deprivation on Neurologic Disorders Disease

Neurologic disorders disease	Role of sleep deprivation (SD)
Alzheimer disease (AD)	Sleep deprivation increases neuronal firing, upregulates BACE1 proteins, and aggravates neuroinflammation and oxidative stress in Alzheimer disease. Sleep deprivation-induced impairment of clearance of toxins through glymphatic pathway leads to the accumulation of amyloid beta and tau proteins. Sleep deprivation has a negative impact on the cholinergic neurons with cognitive dysfunction and impaired memory.
Parkinson disease (PD)	Sleep deprivation causes downregulation of D2/D3 receptors through decreased wakefulness and other altered behavioral effects, which are mediated through the dopaminergic system and result in Parkinson disease-like symptoms. Sleep deprivation-induced impairment of clearance of toxins through glymphatic pathway leads to the accumulation of alpha-synuclein.
Huntington disease	Sleep deprivation disturbs balanced discharge and firing of basal ganglia, which require appropriate REM sleep and wakefulness. Sleep deprivation adversely affects the cerebellar and basal ganglia loops, which may in turn lead to pathogenesis of Huntington disease.
Multiple sclerosis	Disruption of circadian rhythm by sleep deprivation leads to the release of cellular and molecular inflammatory mediators, which cause neuroimmune dysregulation. Sleep deprivation affects the expression of genes involved in the synthesis and maintenance of the myelin proteins.
Stroke	Sleep deprivation aggravates pathophysiology of stroke by increasing the expression of growth-inhibiting genes, neuroinflammation, and oxidative stress. Sleep deprivation following cerebral ischemia increases the levels of growth-inhibiting gene Neurocan, which forms a barrier and inhibits neuronal reconnection and recovery by neuroplasticity.
Epilepsy	Sleep deprivation initiates epileptic seizures and facilitates epileptiform discharges.
Autism spectrum disorders (ASD)	Sleep deprivation is associated with an increase in the severity of autism scores and affects the daily functioning of autism spectrum disorder patients.
Neuropathic pain	In animal experimental studies, sleep deprivation following chronic constriction injury increases microglial activation in the cuneate nucleus and aggravates neuropathic pain induced by nerve injury.

Clinical vignette

A 27-year-old, right-handed woman presented to the sleep center outpatient clinic for initial evaluation of her longstanding excessive daytime sleepiness. For the past 7 years, the patient had been excessively sleepy during the day, falling asleep in sedentary situations. Specifically, she reported falling asleep when grading her students’ papers (she used to fall asleep in class when she was a student herself), in traffic at red lights, when talking to people, and when watching television. She stated that her sleepiness worsened after she began working 2 jobs several years ago. On weekdays, she usually went to bed around 11:30 PM to midnight and got up at 5:30 AM, sleeping a solid 5.5 hours. On weekends, she usually went to bed around 4 AM and slept until noon or 1 PM. When she slept in longer, she felt more refreshed, but was still sleepy and tended to fall asleep, although less frequently, during sedentary situations. She did not take any scheduled naps. She rarely drank caffeinated beverages. She drank alcohol every other weekend. She denied smoking or using recreational drugs. She denied snoring, gasping for air, choking spells, or being told she stops breathing when asleep. She denied cataplexy or hypnagogic hallucinations. On occasion, however, she endorsed the presence of sleep paralysis. She did not have any restless leg symptoms or insomnia.

Past medical history. Noncontributory.

Medications. Fexofenadine hydrochloride and fluticasone propionate.

Social history. She was a teacher and a part-time bartender. She was single and lived with her boyfriend. She did not smoke or abuse alcohol or drugs. She only used alcohol in social situations.

Family history. This was significant for excessive daytime sleepiness in an aunt whom she thought may have had obstructive sleep apnea.

Review of systems. Negative for any psychiatric problems.

Neurologic exam. Completely normal.

During all-night polysomnography, the patient slept for a total of 8.2 hours. Sleep efficiency was normal at 90%. Sleep latency was 5 minutes and REM latency was 63 minutes. No significant sleep-disordered breathing or periodic limb movements of sleep were observed. Urine toxicological screen was normal; a multiple sleep latency test the following day was also normal, with a mean sleep latency of 18.4 minutes.

Soon after the sleep study, she went on her summer break and increased her daily sleep significantly. Her symptoms resolved over 10 days.

Biological basis

Etiology and pathogenesis

	• Chronic sleep deprivation is the most common cause of excessive daytime sleepiness.
	• No pathological process disturbs the patient's ability to initiate or maintain sleep and to remain normally alert during the day following a night of adequate amount of sleep for that person.
	• Several metabolomic biomarkers have been identified in experimental insufficient sleep in human volunteers, of which the most important ones involved ATP binding cassette transporters.
	• Sleep deprivation may have an impact on the hypocretin and orexin secreting neurons, which may explain the resulting excessive sleepiness.

Insufficient sleep syndrome results when an individual persistently, but unwittingly, fails to obtain sufficient to maintain normal alertness throughout the day (02). By far, the most common cause of excessive daytime sleepiness in modern society is chronic sleep deprivation. We sleep 25% less than our forebears did a century ago. There is no evidence that they required more sleep than we do or that we require less sleep than they did. In modern societies, sleep deprivation is often driven by socioeconomic factors. Twenty-four-hour availability of email, shopping, and stock market information on the Internet, as well as 24-hour news networks and television programming, encourage wakefulness at the expense of sleep. More and more businesses, including fast food restaurants, remain open 24 hours a day and unwittingly contribute to their clients’ sleep deprivation. Demands of schools, extracurricular activities, and technology use have increased the incidence of insufficient sleep syndrome among children and adolescents (11).

Sufficient sleep is not measured in absolute hours obtained; rather, it is measured in terms of the amount of sleep that individuals need to maintain alertness relative to the amount of sleep they get. The amount of sleep needed is genetically determined and can vary by individual. Some individuals require 9 hours of sleep per night to maintain normal wakefulness, and if they receive 7 hours, they may become sleepy during the day. Average total sleep time for adults is seven and a half to 8 hours, and epidemiological studies indicate that most adults require 7 to 8 hours of sleep to maintain good health. Sleeping less than 6 hours per night is associated with excessive daytime sleepiness (39). Sleep deprivation is cumulative so that after several nights of moderate sleep restriction, deficits in cognitive performance are equivalent to fewer nights of total sleep deprivation.

The cause of sleepiness in insufficient sleep syndrome is a voluntary restriction of daily sleep time below the individual's specific biological sleep requirements.

Long working hours and shift work increase the risk for insufficient sleep syndrome. Night-shift workers sleep at least 8 hours less each week than do day workers -- an amount equaling the loss of an entire night of sleep every week. A metaanalysis of literature has concluded that health and safety consequences of shift work are like insufficient sleep syndrome, and they are likely to share common mechanisms, but further research is required to determine whether insufficient sleep is the cause of adverse health effects associated with shift work (24).

Studies of healthy normal sleepers have shown that a reduction of sleep time by as little as 2 hours per night produces increased daytime sleepiness as measured by the multiple sleep latency test and that the daytime sleepiness accumulates over successive nights of restricted sleep. Most patients with insufficient sleep syndrome are healthy, normal sleepers who chronically deprive themselves of an adequate daily amount of sleep for professional or personal purposes. The extended sleep times these patients report getting on weekends are not sufficient for full recovery (42).

A study found that cognitive impairment caused by sleep loss varies considerably among individuals and resembles the effect of alcohol intoxication; molecular brain imaging showed that ethanol induces an upregulation of cerebral A1 adenosine receptors with increase up to 26% like in sleep deprivation (14). Therefore, targeting the brain’s adenosine system might enable discovery of countermeasures against cognitive impairment induced by both sleep deprivation and alcohol intoxication.

The essential feature of insufficient sleep syndrome is that the patient is biologically normal; thus, the syndrome should be considered a behavioral one. No pathological process disturbs the patient's ability to initiate or maintain sleep and to remain normally alert during the day following a night of adequate amount of sleep for that person.

The resulting sleep deprivation may have an impact on the hypocretin and orexin secreting neurons’ responses to noradrenaline (18). In this in vitro experiment, it was demonstrated that after a 2-hour sleep deprivation period, the hypocretin and orexin secreting neurons became inhibitory rather than excitatory in response to noradrenaline. This change may be at least in part responsible for the symptom of excessive sleepiness encountered in the insufficient sleep syndrome. Sleep deprivation modulates the gain control and synaptic gating in orexin neurons, which tune them to strong wake-promoting excitatory signals, while dampening weak synaptic inputs to allow transition to sleep in the absence of such strong signals (09).

Biomarkers of insufficient sleep. Biomarkers may be indicators of various disturbances in the human body that may be either causes or effects of insufficient sleep. They may offer insight into pathomechanisms and form the basis of diagnostic tests and help in monitoring the effect of management.

A machine-learning approach using panels of 6 to72 mRNA biomarkers showed that accuracy of classifying acute sleep loss was 92%, but only 57% for classifying chronic sleep insufficiency, and there was little overlap with biomarkers for circadian phase (30).

A crossover laboratory study on humans undergoing experimental insufficient sleep identified 65 metabolomic biomarkers, of which the most important ones involved ATP binding cassette transporters in lipid homeostasis, phospholipid metabolic process, plasma lipoprotein remodeling, and sphingolipid metabolism (13). These biomarkers require further development and validation to advance our understanding of the ill effects of insufficient sleep, improve diagnosis of sleep disorders, and identify targets for interventions to counteract the negative health consequences of insufficient sleep.

Epidemiology

• One third of adults in the United States do not get sufficient sleep.

In the United States, one third of adults do not get sufficient sleep (32). Insufficient sleep syndrome is diagnosed in about 2% of patients presenting at United States sleep disorders centers. In 2008, the Centers for Disease Control and Prevention examined data from over 400,000 subjects throughout the United States and found that 11.1% reported insufficient rest or sleep every day during the preceding 30 days. Females (12.4%) were more likely than males (9.9%), and non-Hispanic blacks (13.3%) were more likely than other racial/ethnic groups, to report insufficient rest or sleep (12). In a cross-sectional study in Japan, using a web-based questionnaire, health-related quality of life showed that 11% of participants aged 20 to 25 years suffer from insufficient sleep syndrome and that the condition is associated with a social status of student or full-time employee (36).

Prevention

• Education regarding the consequences of restricted sleep may reduce the occurrence of insufficient sleep syndrome.

Education regarding the inevitable consequences of restricted sleep and the cumulative effects of such restriction may reduce the occurrence of insufficient sleep syndrome. Although the relation between sleep time and daytime sleepiness seems obvious to most people, socioeconomic circumstances of individuals can lead to a chronic restriction of sleep time and denial of the obvious cause of the symptoms. Individuals at risk include those working 2 or more jobs, those who report to work extremely early, or those with extensive work and homecare responsibilities. As mentioned above, children and adolescents are becoming more and more at risk for developing insufficient sleep syndrome. It is, therefore, important that health care providers of individuals in this age group inquire about their sleep hygiene and counsel patients and families about age-appropriate sleep needs.

Differential diagnosis

Confusing conditions

Insufficient sleep syndrome is differentiated from narcolepsy based on the absence of the accessory signs and symptoms of narcolepsy, from other sleep disorders of excessive sleepiness (ie, sleep apnea syndrome or periodic limb movement disorder based on a polysomnogram showing normal sleep), from insomnia based on absence of difficulty initiating or maintaining sleep, from idiopathic hypersomnia based on shortened habitual sleep times, and from mood disorders based on the normal psychological screening. The differentiation from idiopathic hypersomnia can be a diagnostic challenge because both entities are associated with high sleep efficiency, difficulty on waking in the morning, and reduced latency on the multiple sleep latency test. Idiopathic hypersomnia, however, does not respond to trials of increased amount of sleep at night. The diagnosis should not be made when the sleep environment is not conducive to sleep or when the patient's sleep schedule has been acutely restricted due to work or school deadlines, is irregular, or periodically shifts due to changes in the patient's work schedule. In addition, it should not be made when the patient also has an insomnia complaint. In the survey cited above, 54% of those describing themselves as getting insufficient sleep also had insomnia complaints (10). In other conditions presenting with excessive daytime somnolence, such as environmental sleep disorder and posttraumatic hypersomnia, the clinical history is important in establishing the correct diagnosis (02).

A neuropsychological study has shown that the effect of insufficient sleep at baseline can make a non-injured athlete look like a concussed athlete with sufficient sleep because of cognitive underperformance, which would skew post-concussion comparisons (43). Therefore, there may need to be consideration of prior night's sleep when determining whether a baseline can be used as a valid comparison.

Diagnostic workup

	• Sleep diaries charting the daily amount of sleep
	• Polysomnography

The person complaining of excessive daytime sleepiness should be asked to increase his or her time of sleep during the week preceding the testing. This is usually documented by having him or her fill out sleep diaries or sleep logs that chart the daily amount of sleep.

A nocturnal polysomnographic evaluation can be used to establish the patient's sleep. This evaluation, conducted the night before the multiple sleep latency test, will typically show a rapid sleep onset and maintenance of undisturbed sleep well beyond the patient's reported weekday sleep times. The polysomnogram usually shows a sleep efficiency (sleep time per time in bed) of 90% or greater. A normal progression of sleep stages occurs with unusually low amounts of stage 1 sleep; there is abundant stage 3 and stage 4 sleep and no evidence of a primary sleep disorder, such as obstructive sleep apnea and periodic limb movements of sleep. There may also be increased amounts of REM sleep when the sleep restriction has been extreme or of long duration. A multiple sleep latency test that is administered the following day is usually normal with sleep latencies lasting longer than 10 minutes. However, patients with the insufficient sleep syndrome tend to have decreased mean sleep onset latencies. The naps during the multiple sleep latency test have a greater percentage of stage 2 sleep (of more than 80% of the total time) and may include periods of REM sleep that have latencies of 5 minutes or greater. The medical history and physical examination, drug-use history, and psychological screening are all normal. Fulfilling the diagnostic criteria of insufficient sleep syndrome is challenging in clinical practice. A descriptive study showed that the diagnosis of "definite insufficient sleep syndrome" additionally required objectively confirmed resolution of sleepiness with actigraphy-documented extension of time in bed (05).

Management

• Education of the patient about the reason for excessive sleepiness and instructions to increase nocturnal bedtime or add midday naps, or both.

Management of insufficient sleep syndrome requires a complete evaluation that establishes the presence of excessive daytime sleepiness and rules out the various biological causes of sleepiness. Having reached an accurate diagnosis, the patient can be educated about the reason for excessive sleepiness and instructed to increase nocturnal bedtime or add midday naps, or both, if feasible. Short naps of 10- to 15-minutes duration during the day can improve alertness and performance. With increase of daily sleep time every day of the week, sleepiness should resolve in a matter of weeks. However, patient cooperation is often difficult to attain because the circumstances that led to reduced sleep time may be difficult to alter. If a 2-week or longer trial of extended sleep fails, the diagnosis must be reconsidered.

Stimulants are rarely indicated and are not a substitution for obtaining an adequate amount of sleep. Caffeine is the most used stimulant in the world and may be an effective alternative in managing short-term, limited sleep deprivation. Modafinil and armodafinil have been shown to improve alertness but are approved by the U.S. Food and Drug Administration only in the context of treating sleepiness from shift work disorder, narcolepsy, or residual excessive daytime sleepiness, despite adequate treatment of obstructive sleep apnea.

Sleep deprivation as a therapeutic measure for depression. This article deals with adverse effects of insufficient sleep, and depression is listed among these. However, sleep deprivation has been used for treatment of depression since the 1970s. An fMRI study demonstrated that sleep deprivation reduced functional connectivity between the posterior cingulate cortex and the bilateral anterior cingulate cortex, but enhanced connectivity between the dorsal nexus and the distinct areas in the right dorsolateral prefrontal cortex (08). Although the onset of the therapeutic effect of sleep deprivation is rapid, the duration of action is short-lived. A systematic review of clinical studies combining sleep deprivation with repetitive transcranial stimulation indicates some augmentation of antidepressant effect, but more studies are needed to confirm this (53). A metaanalysis of sleep deprivation in the treatment of bipolar depression found an overall response rate of almost 50%, especially when used with medication, and should guide the future management approaches (17).

Special considerations

Geriatric. Sleep architecture changes with aging. Delta-wave sleep decrease, and the proportion of time spent in lighter sleep increases; this results in increased sleep disruptions. The elderly are more susceptible to effects of sleep deprivation.

Pregnancy

Up to 15% of women report insufficient sleep during pregnancy (40). Insufficient sleep and short sleep duration during pregnancy greatly increase the risk for preterm birth, gestational hyperglycemia, and depression symptoms (35; 40; 21).