Where Clues Lie Sleeping

Sleep disturbances and depression are anything but strange bedfellows. Nearly all depressed individuals experience sleep problems. At least 80% complain of insomnia—difficulty falling or staying asleep. Indeed, early-morning awakening is a hallmark of the mood disorder. Another 15% of the depressed are hypersomniac and sleep excessively.

Yet exactly how disturbed sleep and depression fit together is one of the continuing puzzles of neuroscience. Many mental health experts believe that sleep is a primary window into the brain and holds some key secrets of mood disorders.

For example, says psychiatrist J. Christian Gillin, M.D., about a third of the general population experiences a bout of insomnia perhaps once a year. It's usually short-lived and stress-related. About 10% of the population have more chronic insomnia.

Nevertheless, there is increasing evidence that people who experience chronic insomnia are likely to develop major depression in the future. A professor of psychiatry at the University of California and San Diego Veterans Administration Medical Center, Dr. Gillin points to a study that has tracked former Johns Hopkins medical students over the decades. One major finding: Those who experienced bouts of insomnia in med school developed chronic depression—in some cases 30 years later.

One of the biggest clues to depression may lie in readiness for dream sleep. Normal sleep has a well-defined architecture. EEG studies show that four or five times a night, we cycle through several periods of deepening sleep, then burst into dream sleep, marked by dramatic brain activity and rapid eye movements (along with body-muscle paralysis). But this architecture of sleep goes awry in about 30% of the depressed.

They are on a fast track to dreamland, which sounds like a good thing, but isn't. The time from the first stage of deepening sleep to REM sleep is truncated. Recent studies have shown that people with shortened REM latency often have many first-degree relatives with depression.

"Shortened REM latency seems to be a marker within families for vulnerability to depression," says Dr. Gillin. "It even continues after recovery from depression."

As a result, shortened REM latency may serve as an indicator of those for whom early protective measures might ward off full-blown depression. The only problem is, REM latency can only be detected in a sleep lab, with patients hooked up to brain monitors overnight. Researchers are looking for other ways of detecting disordered dream states.

One of the more curious phenomena in depression is that some of the most popular drugs used to treat it, the serotonin reuptake inhibitors (SSRIs), actually often create sleep problems themselves, especially Paxil and Prozac. And yet many who take SSRIs subjectively feel they are sleeping better as the drug improves their mood.

"Sleep problems with SSRIs often lead to issues of compliance with antidepressant treatment," says Dr. Gillin. Yet he advises patients to bear with it because the depression will ultimately lift and sleep problems diminish.

Among bipolar patients in the depressed phase, however, antidepressant-caused insomnia poses a special risk. Sleep deprivation can switch them into mania. Indeed, many bipolar patients report that manic episodes followed a period in which they were unable to sleep or endured jet lag.

Of all the mysteries of unipolar depression, a condition marked by sleep problems to begin with, the most clinically useful may be the paradoxical observation that keeping people awake may actually help them get better. Sleep deprivation, especially at the end of the night (awakening patients early) improves mood in 30% to 60% of cases, and patients feel better over the day.

"The effect is very robust," says Dr. Gillin. "It's very easy to do. It's very safe, except in bipolar patients. It's extremely inexpensive. And it is the only antidepressant therapy that works immediately." The downside is, once patients sleep again, they wake up depressed the next day.

Although the antidepressant effect is short-lived, Dr. Gillin thinks it's critical that depression can be turned on and off. "If we could understand the mechanism of sleep deprivation, we could probably approach depression treatment in entirely new ways."

In the meantime, a variation on sleep deprivation known as phase advance is making headway. Patients are kept awake all night, then put to bed early the next day, at 5 p.m. for a full eight hours. The next night they go to bed at 7 p.m. for eight hours, 9 p.m. the following night, until they reach an 11 p.m. bedtime. German researchers report this not only improves mood but also maintains the gains.

The theory is that among those vulnerable to depression, sleeping at a critical phase of the night—4:30 to 6:30 a.m.—brings on depression. That is a time when the body begins biologically preparing for function, including increased secretion of stress hormones. "The early-morning awakening that happens in depression," suggests Dr. Gillin, "may be the body's attempt to avoid sleeping in that time."

Phase-advancing sleep may be a useful treatment for depressives who eschew medication. It may also jump-start antidepressant drug therapy. Says Dr. Gillin: "It's an exciting new opportunity."