Medical: Genes play big role in sleep-deprivation responses

Sleep deprivation can be felt in many aspects of our physical and mental health.

But just what amounts to being seriously short on sleep can vary widely from person to person. Some of us seem bright eyed and bushy tailed after only four or five hours of shuteye, while others struggle through the day after snoozing for eight or nine hours.

Most sleep experts say sufficient sleep means sleeping long enough to wake up on our own and feel refreshed and alert for the rest of the day. But long-term sleep surveys suggest middle-aged adults in the U.S. are sleeping about an hour a night less than they did 50 years ago -- 7 to 8 hours a night, down from 8 or 9.

Many things influence sleep duration and how rested we feel, from emotional and physical distress to our age and gender. Many studies have shown that the effects of sleep disruption can linger for days or weeks after returning to a normal schedule. For instance, one recently reported trial that simulated trans-Atlantic jet lag on hamsters found that the animals experienced memory and learning problems for a month after getting back on a regular day-night schedule.

And at least two recent studies suggest that our genes may determine how well rested we feel.

Researchers from the University of Pennsylvania set up an experiment looking at people who have a gene variant closely associated with narcolepsy, a sleep disorder that causes excessive daytime sleepiness.

Having the gene variant doesn't guarantee that someone will develop narcolepsy, though anywhere from 12 percent to 38 percent of people with the special code don't develop the sleep disorder and are considered healthy sleepers. And some people who don't carry the variant also become narcoleptic, although this is fairly rare.

During the study, reported in the journal Neurology in October, the scientists matched up 92 healthy adults without the genetic quirk with 37 healthy adults who carry the variant, but did not have any sleep disorders, in a seven-night test in a sleep lab.

During the first two nights, all the participants spent 10 hours in bed and were well rested. But over the next five nights, their time in bed was limited to four hours a night. During the remaining time, lights were kept on in their room and subjects were told to read, play games or watch movies to help them stay awake.

After each night, the researchers measured sleep quality and self-rated sleepiness the next day. They also tested memory, attention and ability to resist sleep.

Although both groups performed about the same on tests of memory and attention, and ability to resist daytime sleep, those with the gene variant were sleepier and more fatigued after all nights, whether sleep deprived or well-rested. And their sleep was more fragmented and less sound or deep. For instance, those with the variant woke up an average of almost four times on the fifth sleep-deprived night, while those without the variant woke up only twice.

A second study by brain researchers in Seattle took a different approach in a study they reported in November: They looked at what sleep deprivation does to gene expression in the brain.

Working with mice, researchers at the Allen Institute for Brain Science and SRI International identified changes in the expression of 220 sleep-related genes from analysis of 209 brain areas.

They actually tracked the genetic responses in the mice through five behavioral conditions that included sleeping, waking and sleep deprivation, and identified several genes that had not been connected to sleep deprivation before.

Although animals and humans obviously see mood and behavior changes from sleep deprivation, Thomas Kilduff, senior director for neuroscience at SRI, said there has been little understanding of the exact mechanisms by which sleep loss affects brain function.

The study not only documents how extended wakefulness affects gene expression in regions of the brain that control cognitive, emotional and memory functions, but also "describes a molecular anatomical signature of sleep deprivation,'' Kilduff said. "Our findings may contribute to treatments that will help improve sleep quality and reduce problems arising from sleep deprivation."