BETHESDA, MD—Sleep deprivation, a large and growing problem nationwide, can decrease resistance to illness and reduce the brain’s ability to solve problems, according to researchers speaking at a conference on mind-body medicine held at the National Institutes of Health.
“Too little sleep or poor sleep influences every component of the mind,” said Eve Van Cauter, Ph.D., a professor of medicine at the University of Chicago. “Animals who reach a state of exhaustion will go to sleep, but humans struggle to stay awake for extended periods of time. Our society is severely sleep-deprived.”
The brain has two systems to help it keep track of time, Dr. Van Cauter said: a circadian, or natural body clock that is on a 24-hour cycle; it is located in a small nucleus of the hypothalamus called the supercharismatic nucleus. “That clock gives us 24-hour time on a regular basis,” she explained. “It is an endogenous signal that does not require the existence of periodicities in the environment.”
The other bodily system for keeping track of time is a more diffuse, less anatomically focused system, by which the brain keeps track of the duration of wakefulness, she continued. That process, which is often called sleep-wake homeostasis, can be represented graphically as an hourglass.
In this hourglass, sleepiness—as shown by the amount of putative sleep factor—accumulates in the brain with wakefulness and is then released during sleep. These two mechanisms—sleep-wake homeostasis and circadian rhythmicity—interact to control vigilance and sleep-wake behavior.
Sleep-wake homeostasis and circadian rhythm also modulate the activity of the hypothalamus, including the release of the hypothalamic hormone which controls the activity of the pituitary gland, said Dr. Van Cauter. The pituitary glands release six hormones “which, in turn, transmit the influence of the circadian rhythm and sleep-wake homeostasis to literally every aspect of peripheral physiology.”
Some of those hormones, such as prolactin and growth hormone, are crucially dependent on sleep, while others depend on the circadian rhythm. However, she added, the hypothesis that sleep deprivation may have a deleterious effect on the endocrine system was not proven until recently. To test that hypothesis, Dr. Van Cauter and colleagues performed a study in which 11 young male subjects were limited to 4 hours of sleep for six nights, followed by a 7-day recovery period in which they were allowed to sleep for 12 hours nightly.
The researchers found that glucose tolerance was lower during the sleep-deprived period compared with the recovery period. “They took a longer time getting rid of glucose and secreted less insulin,” she said. In fact, the level of glucose tolerance “was consistent with a diagnosis of impaired glucose tolerance, a pre-diabetic condition,” she added. The students who were sleep deprived had an average reading of 1.45 ± 0.31, compared with 2.40 ± 0.41 for the fully rested students.
The immune system is another area that is harmed by lack of sleep, according to James Krueger, Ph.D., professor in the department of veterinary comparative anatomy, pharmacology and physiology at Washington State University, Pullman. “There’s very little direct evidence showing that sleep helps host defenses recuperate from disease,” but some studies have been very evocative.
For instance, when researchers challenged rabbits with either Gram-positive or Gram-negative bacteria and then deprived some of them of sleep, “the animals that slept lived, while those that didn’t, died—not in hour 12 but some days later,” Dr. Krueger said. “That doesn’t tell us per se whether sleep aided in their recuperation, but it’s certainly suggestive.”
Dr. Krueger and his colleagues worked with dwarf rats that had a mutation in the gene for growth hormone-releasing hormone (GHRH), a substance that is thought to be involved in the regulation of sleep-wake activity. The mutation left the rats with a defect in their GHRH signaling mechanism and caused them to sleep less than other rats. When the researchers injected them with the flu virus and followed them for 7 days, they slept less and died earlier than a group of control rats that had also been injected with the virus. “All the test rats were dead by Day 4,” he said.
It seems obvious that a good night’s sleep will improve cognitive function, but proving it scientifically—and it seems almost silly that we think we need to—is another matter.
Robert Stickgold, Ph.D., assistant professor of psychiatry at Harvard University Medical School, Cambridge, Mass., asked more than 200 Harvard students to participate in a visual test in which they were trained to identify diagonal slashes projected on a computer screen along with other similar images. “The test takes about 1 to 1.5 hours,” he explained. “If we brought them back at 3, 6, 9, and 12 hours on the same day, there was no improvement (in performance), but if we brought them back after a night of sleep, they did better.”
“If we make the students take the test every three hours all day long, their performance gets worse and worse and they like us less and less.” If, instead, the investigators let the students go to sleep at night and then brought them in again the next day to test them, their test results depended greatly on how well they slept the night before, he continued.
“Slow-wave sleep, the deep sleep of the night, shows a high correlation with improved performance” as long as it is obtained in the first two hours of the night. Slow-wave sleep in the remainder of the night has no effect on performance at all, Dr. Stickgold said.
Rapid-eye-movement (REM) sleep is also important. But in contrast to slow-wave sleep, REM sleep appears critical in the last quarter of the night, and shows no correlation with improved performance if obtained in the first six hours of the night. “This explains 80% of the inter-subject variability [in test results] —just these two parameters,” Dr. Stickgold said.
Dr. Stickgold sees learning as a three-step process. “First we’ve got training, where some plastic changes have to be occurring in the brain,” he said. “This [is] a non-stable, fragile form of plastic change, because we know if we don’t get sleep in that next night we’re going to lose those changes. Then there are two subsequent changes, one in slow-wave sleep, and one in REM sleep.”
The researchers tried to use money to motivate the students to improve their scores without getting any additional sleep. But that strategy failed, Dr. Stickgold said. “It may be that once the brain has loaded up its buffer of information, it can’t receive more until it has reallocated the information and can allow new information to come in.”
During a question-and-answer session, Dr. Stickgold noted that American culture is one that encourages sleep deprivation. “[Microsoft founder] Bill Gates is quoted as saying that his programmers are so rough and tough that they can program for 72 hours straight,” he said. “Of course, the product of that is Windows.”
