Excessive daytime sleepiness (EDS) can lead to car accidents and work-related injuries and may increase risk of stroke and heart disease

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Everyone feels tired at times, but up to 20 percent of U.S. adults report feeling so sleepy during the day that it interferes with daily activities, including working, having meals or carrying on conversations.

Excessive daytime sleepiness (EDS) can lead to car accidents and work-related injuries and may increase risk of stroke and heart disease.

Rates of EDS vary by race/ethnicity, but the basis for these differences is not well understood.

A new, multi-ethnic study led by investigators from Brigham and Women’s Hospital explores associations between daytime sleepiness and epigenetic modifications – measurable, chemical changes that may be influenced by both environmental and genetic factors.

The team finds tantalizing clues about EDS, laying a foundation for larger scale studies of diverse populations.

Results of the study are published in the journal Sleep.


Excessive daytime sleepiness (EDS) is a common problem that is important to recognize and address.

Initial steps in management are generally straightforward and only the most advanced cases would require referral to a subspecialist.

Of particular concern is that of driving safety.

There is a broad differential diagnosis for conditions contributing to EDS but a few common conditions account for the majority of clinical presentations.

Subjective self-reporting will often lead to identification of potential problems, but this is often unreliable.

Traditional neurophysiologic tests can help in objectively quantifying symptoms but current tests are not always practical clinically and may have little validation in real world situations.

There are many treatment options that should generally be able to sufficiently manage most patients presenting with hypersomnolence. 

See Figure 1 for the general approach to clinical management.

The first step is identifying EDS.

The individual identifies EDS when it is creating a problem in their life such as falling asleep in inappropriate settings such as driving.

The situation is even more concerning when colleagues, friends, or family have identified concerns, as subjective reporting may lead some individuals to deny the problem.

Sleepiness can be hard to quantify as the subjective experience varies between individuals.

In general, observable behaviors and objective measures are better used wherever possible. A physician may first identify sleepiness by seeing patients asleep in the waiting room.

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Figure 1

Clinical approach to excessive daytime sleepiness.

Some patients may not identify sleepiness but will identify their problem as fatigue. Fatigue is vague word and may reflect sleepiness but also reflects attributes including pain, disability, and depression.

There can be significant overlap in depression and EDS. Being tired, feeling run down, and having low energy may be seen in both.

Clinically, tearfulness or hopelessness may identify more prominent mood symptoms.

There are many causes of EDS [1].

The first condition to identify is that of insufficient sleep.

Most people need around 7–9 hours of sleep and many get less.

If someone needs to wake up by an alarm clock, they are most likely getting insufficient sleep time.

Tracking sleep times in the form of a sleep log can be helpful although it is important for the participant to record activities every day and not simply guess or summarize at the end of a longer period.

Actigraphy, smartphones, and fitness devices can also be helpful tools to estimate sleep.

Patients with shift work may develop profound sleepiness due to cumulative sleep deficit as well as being awake at times when there is a natural circadian tendency for profound sleepiness, for example, 03:00–05:00.

Metabolic problems can also contribute to sleepiness.

Patients with anemia and hypothyroidism commonly report fatigue.

A number of other metabolic disorders can produce sleepiness including hepatic and renal failure.

Electrolyte abnormalities or systemic inflammation can also contribute.

These conditions are generally identified on a basic medical examination and blood work.

Medications are another common contributor to sleepiness; psychoactive medications are particularly problematic.

Many antidepressants, anxiolytics, pain medications, and antiepileptics impair alertness.

Over-the-counter medications must also be considered; antihistamines are associated with somnolence, for example.

Drugs and alcohol may also contribute to sleepiness.

After these factors are addressed, sleep apnea (SA) will be one of the most common presenting conditions.

Increased weight, enlarged neck circumference, and airway abnormalities may be identified in addition to a report of snoring.

The upper airway resistance syndrome (UARS) should also be carefully considered. Even if there is no significant oxygen desaturation, or scored hypopneas, sleep may be fragmented by mild obstructive events and sleep fragmentation and consequent daytime sleepiness results.

Less commonly, narcolepsy will be responsible for sleepiness.

Narcolepsy occurs in about 1 in 2000 persons. While this is rare, these patients are more likely to present to a sleep specialist. EDS is the only symptom that must be present to establish a diagnosis.

This can occur in the absence of cataplexy, sleep paralysis, and sleep onset hallucinations but if these symptoms are present, the condition is more likely.

Brain abnormalities can also impair alertness. Distortion of midline projecting systems by a mass lesion is notorious for producing somnolence.

By disrupting midline projecting systems, head injuries can cause a reduction in orexin/hypocretin signalling similar to that seen in narcolepsy [2].

Many neurodegenerative conditions are associated with sleepiness. A careful neurologic examination may identify these conditions. Neuroimaging is suggested in most of these situations.


“Looking in diverse populations benefits all populations,” said corresponding author Tamar Sofer, Ph.D., associate biostatistician and director of the Biostatistics core of the program in sleep medicine epidemiology in the Division of Sleep and Circadian Disorders at the Brigham.

“We need more studies in ethnically diverse populations, especially for sleep disorders like EDS where there are differences across populations.

When we focus narrowly, we have less opportunity to make discoveries.”

For the current study, investigators used data from 619 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) and 483 participants in the Cardiovascular Health Study (CHS).

Participants completed a sleep exam, which included questions to assess the likelihood of dozing off during a variety of daily activities.

Using this questionnaire, the team could assign a score to each participant on the Epworth Sleepiness Scale, a screening tool for EDS.

The team also collected data on DNA methylation – the most commonly studied epigenetic marker.

DNA methylation occurs when a methyl group is added at a specific DNA site, influencing the activity of a particular gene.

Among the MESA participants, the team found four sites of DNA methylation that were associated with sleepiness: one across all race/ethnic groups and three among African Americans only.

Two of these associations were nominally replicated in the CHS population.

When the team looked at only African American participants from both studies, they found 14 DNA methylation sites associated with sleepiness.

Some of these sites were found in genes that have been previously reported as associated with sleep traits.

The team found additional overlap in a follow-up study of genes associated with sleepiness in data from the UK Biobank.

DNA methylation is thought to be influenced by a variety of environmental factors, such as exposure to air pollution, stress and diet, as well as a person’s genetics.

“We’ve uncovered multiple sites, but our search is continuing,” said Sofer.

“What’s interesting about epigenetics is that it’s modifiable – lifestyle exposures can change these markers.

If we can eventually use epigenetics as a readout or marker for excessive sleepiness and understand what causes these changes, we may be able to find ways to intervene to alleviate the burden of EDS.”

Journal information: Sleep
Provided by Brigham and Women’s Hospital

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