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Overview
 Sleepwhich is defined behaviorally by the normal suspension of consciousness
and electrophysiologically by specific brain wave criteriaconsumes fully
a third of our lives. Sleep occurs in all mammals, and probably all vertebrates.
We crave sleep when deprived of it, and, to judge from animal studies,
continued sleep deprivation can ultimately be fatal. Surprisingly, however,
this peculiar state is not the result of a simple diminution of brain
activity; rather, sleep is a series of precisely controlled brain states,
and in some of these the brain is as active as it is when people are
awake. The sequence of sleep states is governed by a group of brainstem
nuclei that project widely throughout the brain and spinal cord. The
reason for high levels of brain activity during some phases of sleep,
the significance of dreaming, and the basis of the restorative effect
of sleep are all topics that remain poorly understood. The clinical importance
of sleep is obvious from the prevalence of sleep disorders (insomnias).
Each year about 40 million Americans suffer from chronic sleep disorders
and an additional 20 million experience occasional sleeping problems.
An estimated 20% of the U.S. population experience during their lifetime
some kind of sleep disorder. These problems range from simply annoying
to life threatening. The most common problems are insomnia, sleep apnea, "restless
legs" syndrome, and narcolepsy.
Insomnia, or the inability to sleep, has many causes. Short-term
insomnia can arise from stress, jet lag, or simply drinking too much
coffee. These problems can usually be prevented by improving sleep habits,
avoiding stimulants like caffeine at night, and in some cases taking
sleep-promoting medications. More serious insomnia is associated with
psychiatric disorders such as depression that presumably affect the balance
between the cholinergic, adrenergic, and serotinergic systems that control
the onset and duration of the sleep cycles. Long-term insomnia is a particular
problem in the elderly because they sleep less, are subject to more depression,
and frequently take medications that affect the relevant neurotransmitter
systems.
Sleep apnea refers to interrupted breathing during sleep that
affects about 18 million Americans, most often obese males in middle
age. A person suffering from sleep apnea may awaken hundreds of times
during the night, with the result that they have little or no slow-wave
sleep and spend less time in REM sleep. Consequently, these individuals
are chronically tired in the daytime and often suffer from depression
that exacerbates the problem. In some high-risk individuals, sleep apnea
may even lead to sudden death from respiratory arrest during sleep. The
underlying problem is that the airway collapses during breathing, thus
blocking air flow. In normal sleep, breathing slows and muscle tone decreases
throughout the body, including the tone of the pharynx. If the brainstem
circuitry regulating commands to the chest wall or to pharyngeal muscles
is affected, or if the airway is compressed because of the weight on
it during sleep, the pharynx tends to collapse as the muscles relax during
breathing. As a result, oxygen levels decrease and the ensuing reflex
to inspire more air awakens people suffering from this disorder.
A third sleep disorder is "restless legs syndrome," a
familial disorder causing unpleasant crawling, prickling, or tingling
sensations in the legs and feet, and an urge to move them about for relief.
This problem is surprisingly common, affecting about 12 million (mostly
elderly) Americans. The result is constant leg movement during the day
and fragmented sleep patterns at night. The neurobiology of this particular
problem is not understood, but the problem often can be relieved by drugs
that inhibit the release of dopamine.
The sleep disorder that is best understood in neurobiological terms
is narcolepsy, a chronic disorder that affects about 250,000 people
in the United States. Individuals with narcolepsy have frequent "REM
sleep attacks" during the day, in which they enter REM sleep from wakefulness
without going through non-REM sleep. Such individuals may become cataplectic
during these episodes, and can fall down (cataplexy refers to a temporary
loss of muscle control). Insight into the causes of narcolepsy have come
from studies of dogs suffering from a genetic disorder similar to the
human disease. In these animals, narcolepsy is caused by a mutation of
the hypocretin receptor 2 gene (Hcrtr2). Hypocretins (or orexins)
are neuropeptides homologous to secretin, which is found exclusively
in cells in the tuberal region of the hypothalamus. These hypothalamic
cells project to the reticular formation, the locus coeruleus and the
dorsal raphe nucleus, all of which control various aspects of sleep.
The evidence in dogs suggests that the Hcrtr2 mutation cause a
hyperexcitability of the neurons that generate REM sleep, and/or impairment
of the circuits that inhibit REM sleep |
Chronic Fatigue Syndrome
