OT: Sleep Loss Affects More than the Brain

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Sleep Loss Affects More than the Brain

This article is from the September-October issues of The Dana Foundation's

Brain Work: The Neuroscience Newsletter.

Researchers have known that too little sleep affects mental performance.

Now they are finding that sleep loss affects a whole lot more, including

the immune system, cardiovascular health, and even hunger regulation.

Epidemiologic studies around the world show that time spent in sleep is

linked to all causes of death and to conditions that include cardiovascular

risk, hypertension, diabetes, and stroke, says Dinges, a sleep

researcher at the University of Pennsylvania School of Medicine in

Philadelphia. " The risk goes up when you sleep below seven hours or above

eight, especially below seven, " he says.

Several large studies have been designed to look at the impact of sleep

disturbance on physical health, including the Sleep Heart Health Study, a

multicenter study implemented by the National Heart, Lung, and Blood

Institute at the National Institutes of Health. After compiling the

complete health history of more than 1,000 volunteers and obtaining basic

information such as weight and blood pressure, the researchers fitted each

participant with equipment that enabled the researchers to measure

electrical currents in the brain, oxygen saturation in their breath, and

chest and body movement.

Because different stages of sleep are associated with different electrical

patterns as measured by electroencephalogram (EEG), the researchers could

see who slept soundly and who had broken sleep. Eyal Shahar of the

University of Minnesota, one of the Sleep Heart Health Study leaders, found

that people who had severe sleep apnea, in which they stop breathing for a

short period of time repeatedly during the night, were 42 percent more

likely to have heart problems and 58 percent more likely to suffer a stroke

than participants who did not have the disorder. In a separate study,

scientists found that patients treated for sleep apnea had a lower risk of

heart attack and stroke, and were less likely to require bypass surgery

than those who had untreated sleep apnea of a similar severity. Although

neither of these studies shows definitively that cardiovascular problems

are caused by sleep apnea or disrupted sleep, the data suggest that there

is an important interaction between the two processes.

Immune System Link

To find out what links sleep and cardiovascular problems, scientists are

watching what happens to healthy people after sleep deprivation, Dinges

says. " In some individuals there is a clear increase in inflammatory

markers " after a week of getting only four or five hours of sleep per

night, he says. Proinflammatory cytokines, including interleukin-6, become

elevated in response to sleep loss. These cytokines likely trigger a chain

of other inflammatory proteins, such as C-reactive protein, which is a

marker for cardiovascular inflammation and risk.

The relationship between sleep, cytokines, and immune system function is

not simple, however. In 1994, Dinges found that after sleep deprivation,

young adults produced an abnormally high number of white blood cells, as if

they were fighting an infection, although no pathogen was present. Such a

strong response could lead to an increase in proinflammatory cytokines.

On the other hand, Eve van Cauter, a professor of medicine at the

University of Chicago, and colleagues found that young men who were

sleep-deprived produced a less robust response to an influenza vaccination

than did those who were fully rested. Even after ten nights of adequate

sleep following the immunization, the effect was still visible, suggesting

that some aspect of the immune response was compromised significantly.

Metabolic Effects

Studies in healthy adults have also shown a strong correlation between

sleep and body mass index. In 2004, Shahrad Taheri, Emmanuel Mignot, and

colleagues at Stanford University showed that people who slept fewer than

eight hours had an increased body mass index in proportion to their

decreased sleep, as well as altered levels of hormones that regulate

metabolism and hunger. Specifically, volunteers who typically slept five

hours per night had a 15 percent reduction in leptin, a hormone that

suppresses appetite, and a 15 percent increase in ghrelin, a hormone that

stimulates appetite.

In other words, people who slept less tended to feel hungrier than those

who slept 8 hours. In one experiment, which van Cauter reported in June at

the annual sleep research meeting, men consumed 26 percent more calories

during periods of extended wakefulness when they got only five hours of

sleep per night than they did during recovery periods in which they were

allowed to sleep between 10 and 12 hours per night.

Researchers calculate that the 15 percent change in leptin could lead to

about 500 extra calories per day, significantly more than the body consumes

by staying awake. " After several days that could lead to some serious

weight gain, " says Knutson, a postdoctoral fellow in van Cauter's

group.

The research group also reported at the June meeting that sleep quality had

an impact on metabolic hormones. They brought nine healthy young adults

into the sleep lab for five nights. The first two nights, the volunteers

were allowed to sleep normally, but during the following three nights the

researchers played intermittent loud noises so that the volunteers

experienced " microarousals. "

With these interruptions, the volunteers never reached the deep sleep

stages that are characterized by slow wave activity on an EEG monitor.

Sleep fragmentation and suppression of slow-wave sleep reduced insulin

sensitivity in these volunteers. Because insulin resistance is considered a

prediabetic condition, the work hints at how sleep disorders might increase

a person's risk of developing type 2 diabetes, which has been shown

previously to correlate with chronic sleep loss in epidemiological studies.

Perchance to Think

In addition to these physiological changes, scientists find dramatic

alterations in cognition after people are either completely deprived of

sleep or have several nights with less sleep than normal. When volunteers

used a computer task that requires constant attention, Dinges's group saw a

steady decline in performance among subjects who slept less. The deficits

increased as the number of nights of sleep loss accumulated: people who

have short sleep for a couple of weeks can be as impaired cognitively as

someone who has been awake for two or three days straight, but they do not

know it, Dinges says.

In a separate study, the team found that, after 36 hours of complete sleep

deprivation, those who were asked to work on the task for a longer period

of time performed worse than those similarly sleep-deprived who worked on

it for less time.

" Even though this is something that people say happens to them in the real

world, and is sort of obvious, it has rarely been studied or documented, "

Dinges says. Remarkably, those who worked harder also spent more time in

slow-wave sleep during the recovery period. That observation supports the

notion that the brain's requirement for slow-wave sleep is proportional to

brain use during waking hours, which researchers refer to as a

use-dependent requirement for sleep (see " A Model of Sleep's Role in the

Brain " ).

Scientists used to say that sleep was of, by, and for the brain, but recent

findings suggest otherwise. Sleep may have initially evolved to take care

of the brain, but many other systems now appear to rely on it for

regulation and stabilization.

" Sleep is not just one thing, " Knutson says. " For a long time people

thought that you get sleepy and maybe your brain is not there. But that's

not it. It affects the whole body. "

- Rabiya S. Tuma is a science and medical writer in Berkeley, Calif.

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www.dana.org; the DANA Foundation’s publications relate to the brain.