Circadian rhythms are regular changes in mental and physical characteristics that occur in the course of a day (circadian is Latin for "around a day"). Most circadian rhythms are controlled by the body's biological "clock." This clock, called the suprachiasmatic nucleus or SCN, is actually a pair of pinhead-sized brain structures that together contain about 20,000 neurons. The SCN rests in a part of the brain called the hypothalamus, just above the point where the optic nerves cross. Light that reaches photoreceptors in the retina (a tissue at the back of the eye) creates signals that travel along the optic nerve to the SCN.
Signals from the SCN travel to several brain regions, including the pineal gland, which responds to light-induced signals by switching off production of the hormone melatonin. The body's level of melatonin normally increases after darkness falls, making people feel drowsy. The SCN also governs functions that are synchronized with the sleep/wake cycle, including body temperature, hormone secretion, urine production, and changes in blood pressure.
By depriving people of light and other external time cues, scientists have learned that most people's biological clocks work on a 25-hour cycle rather than a 24-hour one. But because sunlight or other bright lights can reset the SCN, our biological cycles normally follow the 24-hour cycle of the sun, rather than our innate cycle. Circadian rhythms can be affected to some degree by almost any kind of external time cue, such as the beeping of your alarm clock, the clatter of a garbage truck, or the timing of your meals. Scientists call external time cues zeitgebers (German for "time givers").
When travelers pass from one time zone to another, they suffer from disrupted circadian rhythms, an uncomfortable feeling known as jet lag. For instance, if you travel from California to New York, you "lose" 3 hours according to your body's clock. You will feel tired when the alarm rings at 8 a.m. the next morning because, according to your body's clock, it is still 5 a.m. It usually takes several days for your body's cycles to adjust to the new time.
To reduce the effects of jet lag, some doctors try to manipulate the biological clock with a technique called light therapy. They expose people to special lights, many times brighter than ordinary household light, for several hours near the time the subjects want to wake up. This helps them reset their biological clocks and adjust to a new time zone.
Symptoms much like jet lag are common in people who work nights or who perform shift work. Because these people's work schedules are at odds with powerful sleep-regulating cues like sunlight, they often become uncontrollably drowsy during work, and they may suffer insomnia or other problems when they try to sleep. Shift workers have an increased risk of heart problems, digestive disturbances, and emotional and mental problems, all of which may be related to their sleeping problems. The number and severity of workplace accidents also tend to increase during the night shift. Major industrial accidents attributed partly to errors made by fatigued night-shift workers include the Exxon Valdez oil spill and the Three Mile Island and Chernobyl nuclear power plant accidents. One study also found that medical interns working on the night shift are twice as likely as others to misinterpret hospital test records, which could endanger their patients. It may be possible to reduce shift-related fatigue by using bright lights in the workplace, minimizing shift changes, and taking scheduled naps.
Many people with total blindness experience life-long sleeping problems because their retinas are unable to detect light. These people have a kind of permanent jet lag and periodic insomnia because their circadian rhythms follow their innate cycle rather than a 24-hour one. Daily supplements of melatonin may improve night-time sleep for such patients. However, since the high doses of melatonin found in most supplements can build up in the body, long-term use of this substance may create new problems. Because the potential side effects of melatonin supplements are still largely unknown, most experts discourage melatonin use by the general public.
Sleep and sleep-related problems play a role in a large number of human disorders and affect almost every field of medicine. For example, problems like stroke and asthma attacks tend to occur more frequently during the night and early morning, perhaps due to changes in hormones, heart rate, and other characteristics associated with sleep. Sleep also affects some kinds of epilepsy in complex ways. REM sleep seems to help prevent seizures that begin in one part of the brain from spreading to other brain regions, while deep sleep may promote the spread of these seizures. Sleep deprivation also triggers seizures in people with some types of epilepsy.
Neurons that control sleep interact closely with the immune system. As anyone who has had the flu knows, infectious diseases tend to make us feel sleepy. This probably happens because cytokines, chemicals our immune systems produce while fighting an infection, are powerful sleep-inducing chemicals. Sleep may help the body conserve energy and other resources that the immune system needs to mount an attack.
Sleeping problems occur in almost all people with mental disorders, including those with depression and schizophrenia. People with depression, for example, often awaken in the early hours of the morning and find themselves unable to get back to sleep. The amount of sleep a person gets also strongly influences the symptoms of mental disorders. Sleep deprivation is an effective therapy for people with certain types of depression, while it can actually cause depression in other people. Extreme sleep deprivation can lead to a seemingly psychotic state of paranoia and hallucinations in otherwise healthy people, and disrupted sleep can trigger episodes of mania (agitation and hyperactivity) in people with manic depression.
Sleeping problems are common in many other disorders as well, including Alzheimer's disease, stroke, cancer, and head injury. These sleeping problems may arise from changes in the brain regions and neurotransmitters that control sleep, or from the drugs used to control symptoms of other disorders. In patients who are hospitalized or who receive round-the-clock care, treatment schedules or hospital routines also may disrupt sleep. The old joke about a patient being awakened by a nurse so he could take a sleeping pill contains a grain of truth. Once sleeping problems develop, they can add to a person's impairment and cause confusion, frustration, or depression. Patients who are unable to sleep also notice pain more and may increase their requests for pain medication. Better management of sleeping problems in people who have other disorders could improve these patients' health and quality of life.
At least 40 million Americans each year suffer from chronic, long-term sleep disorders each year, and an additional 20 million experience occasional sleeping problems. These disorders and the resulting sleep deprivation interfere with work, driving, and social activities. They also account for an estimated $16 billion in medical costs each year, while the indirect costs due to lost productivity and other factors are probably much greater. Doctors have described more than 70 sleep disorders, most of which can be managed effectively once they are correctly diagnosed. The most common sleep disorders include insomnia, sleep apnea, restless legs syndrome, and narcolepsy.
Almost everyone occasionally suffers from short-term insomnia. This problem can result from stress, jet lag, diet, or many other factors. Insomnia almost always affects job performance and well-being the next day. About 60 million Americans a year have insomnia frequently or for extended periods of time, which leads to even more serious sleep deficits. Insomnia tends to increase with age and affects about 40 percent of women and 30 percent of men. It is often the major disabling symptom of an underlying medical disorder.
For short-term insomnia, doctors may prescribe sleeping pills. Most sleeping pills stop working after several weeks of nightly use, however, and long-term use can actually interfere with good sleep. Mild insomnia often can be prevented or cured by practicing good sleep habits.. For more serious cases of insomnia, researchers are experimenting with light therapy and other ways to alter circadian cycles.
Sleep apnea is a disorder of interrupted breathing during sleep. It usually occurs in association with fat buildup or loss of muscle tone with aging. These changes allow the windpipe to collapse during breathing when muscles relax during sleep. This problem, called obstructive sleep apnea, is usually associated with loud snoring (though not everyone who snores has this disorder). Sleep apnea also can occur if the neurons that control breathing malfunction during sleep.
During an episode of obstructive apnea, the person's effort to inhale air creates suction that collapses the windpipe. This blocks the air flow for 10 seconds to a minute while the sleeping person struggles to breathe. When the person's blood oxygen level falls, the brain responds by awakening the person enough to tighten the upper airway muscles and open the windpipe. The person may snort or gasp, then resume snoring. This cycle may be repeated hundreds of times a night. The frequent awakenings that sleep apnea patients experience leave them continually sleepy and may lead to personality changes such as irritability or depression. Sleep apnea also deprives the person of oxygen, which can lead to morning headaches, a loss of interest in sex, or a decline in mental functioning. It also is linked to high blood pressure, irregular heartbeats, and an increased risk of heart attacks and stroke. Patients with severe, untreated sleep apnea are two to three times more likely to have automobile accidents than the general population. In some high-risk individuals, sleep apnea may even lead to sudden death from respiratory arrest during sleep.
An estimated 18 million Americans have sleep apnea. However, few of them have had the problem diagnosed. Patients with the typical features of sleep apnea, such as loud snoring, obesity, and excessive daytime sleepiness, should be referred to a specialized sleep center that can perform a test called polysomnography. This test records the patient's brain waves, heartbeat, and breathing during an entire night. If sleep apnea is diagnosed, several treatments are available. Mild sleep apnea frequently can be overcome through weight loss or by preventing the person from sleeping on his or her back. Other people may need special devices or surgery to correct the obstruction. People with sleep apnea should never take sedatives or sleeping pills, which can prevent them from awakening enough to breathe.
Restless legs syndrome (RLS), a familial disorder causing unpleasant crawling, prickling, or tingling sensations in the legs and feet and an urge to move them for relief, is emerging as one of the most common sleep disorders, especially among older people. This disorder, which affects as many as 12 million Americans, leads to constant leg movement during the day and insomnia at night. Severe RLS is most common in elderly people, though symptoms may develop at any age. In some cases, it may be linked to other conditions such as anemia, pregnancy, or diabetes.
Many RLS patients also have a disorder known as periodic limb movement disorder or PLMD, which causes repetitive jerking movements of the limbs, especially the legs. These movements occur every 20 to 40 seconds and cause repeated awakening and severely fragmented sleep. In one study, RLS and PLMD accounted for a third of the insomnia seen in patients older than age 60.
RLS and PLMD often can be relieved by drugs that affect the neurotransmitter dopamine, suggesting that dopamine abnormalities underlie these disorders' symptoms. Learning how these disorders occur may lead to better therapies in the future.
Narcolepsy affects an estimated 250,000 Americans. People with narcolepsy have frequent "sleep attacks" at various times of the day, even if they have had a normal amount of night-time sleep. These attacks last from several seconds to more than 30 minutes. People with narcolepsy also may experience cataplexy (loss of muscle control during emotional situations), hallucinations, temporary paralysis when they awaken, and disrupted night-time sleep. These symptoms seem to be features of REM sleep that appear during waking, which suggests that narcolepsy is a disorder of sleep regulation. The symptoms of narcolepsy typically appear during adolescence, though it often takes years to obtain a correct diagnosis. The disorder (or at least a predisposition to it) is usually hereditary, but it occasionally is linked to brain damage from a head injury or neurological disease.
Once narcolepsy is diagnosed, stimulants, antidepressants, or other drugs can help control the symptoms and prevent the embarrassing and dangerous effects of falling asleep at improper times. Naps at certain times of the day also may reduce the excessive daytime sleepiness.
In 1999, a research team working with canine models identified a gene that causes narcolepsy–a breakthrough that brings a cure for this disabling condition within reach. The gene, hypocretin receptor 2, codes for a protein that allows brain cells to receive instructions from other cells. The defective versions of the gene encode proteins that cannot recognize these messages, perhaps cutting the cells off from messages that promote wakefulness. The researchers know that the same gene exists in humans, and they are currently searching for defective versions in people with narcolepsy.
Sleep research is expanding and attracting more and more attention from scientists. Researchers now know that sleep is an active and dynamic state that greatly influences our waking hours, and they realize that we must understand sleep to fully understand the brain. Innovative techniques, such as brain imaging, can now help researchers understand how different brain regions function during sleep and how different activities and disorders affect sleep. Understanding the factors that affect sleep in health and disease also may lead to revolutionary new therapies for sleep disorders and to ways of overcoming jet lag and the problems associated with shift work. We can expect these and many other benefits from research that will allow us to truly understand sleep's impact on our lives.
