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The search for the genetic roots of depression has led scientists to the bedroom, where they've discovered that people with a particular type of sleep pattern and a family history of depression are twice as likely to become depressed as relatives who don't sleep the same way. The link is true even in family members who have no history of the disease themselves and who feel absolutely fine.
The findings come from a team led by University of Rochester Medical Center psychologist Donna Giles, Ph.D., who uses sleep as a window to study the origins of depression. Her latest work, part of a study that stretches back to 1985, builds on the link between sleep and depression to try and identify a specific brain chemical that may be at the root of depression for some patients.
Giles and her colleagues have found that the speed with which people fall into dream sleep can indicate people who are more prone to depression. In families where at least one person is depressed, people who enter dream sleep less than 60 minutes after falling asleep are more than twice as likely to become depressed than relatives who enter dream sleep in the more common 90-minute range.
"This is the first physiological marker that predicts the onset of depression even in someone who has never had the illness," says Giles, whose work is funded by the National Institute of Mental Health. "While doctors know that depression in one's family can make a person more prone to the disorder, understanding the link in detail has been difficult. Right now, doctors can't predict who will become depressed."
Dream sleep, or rapid-eye-movement (REM) sleep, is the fifth of five stages of sleep that we cycle through several times each night. Our brain activity slows progressively throughout the first four stages, and then suddenly in REM sleep, our brains kick into high gear. "In REM sleep, brain activity looks just as it does when we're awake, but our muscles are inhibited," says Giles, professor of psychiatry. "It's also known as paradoxical sleep, because the brain behaves as if we're awake."
The sleep disturbances that many depressed people have, such as sleeping more than usual or having difficulty falling asleep, are apparent to patients and families. But falling into REM sleep quickly, a trait known as "short REM latency," isn't obvious in everyday life. "You wouldn't know you have it unless you were tested in a sleep laboratory," Giles says. "Your sense of time is mixed up when you sleep, so you can't really remember how fast you fell asleep and started dreaming."
It takes the technology of a sleep laboratory to find short REM latency. Along with colleagues David Kupfer at the University of Pittsburgh, Howard Roffwarg at the University of Mississippi, and John Rush at the University of Texas Southwestern Medical Center in Dallas, Giles has studied the sleep patterns of 352 people in 70 families; in some families depression has affected at least one person, and in other families there is no history of depression. The brain activity, muscle activity, and eye movements of research subjects are monitored while they sleep for three nights; participants are also interviewed by phone at least once per year. Giles is currently expanding the study to include additional family members.
Among depressed people, about 30 to 40 percent of outpatients and 60 to 70 percent of depressed patients in the hospital have short REM latency, while approximately 20 percent of people who are not depressed have it. Since not all depressed people have short REM latency, and many healthy people do, the trait cannot be used to diagnose depression. But in families where depression has been identified, it might provide a way for some family members to find out if they are especially vulnerable.
"With this information, a person might be able to take some protective measures, such as becoming more educated about the first symptoms of depression," she says. Since it may not be practical to run all relatives of a depressed person through a sleep laboratory, Giles says an alternative would be to monitor the sleep patterns of a depressed person for two or three nights. If that person has short REM latency, his or her relatives are four times as likely to share the sleep pattern and the increased likelihood of depression.
Giles and several colleagues hope to use their work as a basis to launch a large multi-site trial on the genetics of depression. In the meantime, in the latest phase of the current study, Giles and colleague Michael Perlis, Ph.D., are testing whether Aricept, the same medicine used by patients with Alzheimer's disease to stave off problems with memory, can change sleep patterns. Aricept boosts the amount of the brain chemical acetylcholine, which triggers REM sleep and improves memory.
Scientists will give research participants a small dose of the medicine and will monitor their sleep experiences, checking out the hypothesis that those with a tendency to enter dream sleep quickly are more sensitive to acetylcholine. If so, that would suggest that the chemical may play a fundamental role in somehow predisposing people to depression.
Press Release from: University of Rochester