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Properly Timed Light, Melatonin Lift Winter Depression by Syncing Rhythms

Science Update

Most Seasonal Affective Disorder (SAD) symptoms stem from daily body rhythms that have gone out-of-sync with the sun, a NIMH-funded study has found. The researchers propose that most patients will respond best to a low dose of the light-sensitive hormone melatonin in the afternoon in addition to bright light in the morning. Rhythms that have lost their bearings due to winter's late dawn and early dusk accounted for 65 percent of SAD symptoms; re-aligning them explained 35 percent of melatonin's antidepressant effect in patients with delayed rhythms, the most common form of SAD, report NIMH grantee Alfred Lewy, M.D., Ph.D., and colleagues at the Oregon Health & Science University, online, April 28, 2006, in the Proceedings of the National Academy of Sciences.

SAD affects many people in northern latitudes in winter, especially young women, and is usually treated with bright light in the morning. The pineal gland, located in the middle of the brain, responds to darkness by secreting melatonin, which re-sets the brain's central clock and helps the light/dark cycle re-set the sleep/wake cycle and other daily rhythms. Lewy and colleagues pinpointed how rhythms go astray in SAD and how they can be re-set by taking melatonin supplements at the right time of day. The findings strengthen the case for daily rhythm mismatches as the cause of SAD.

The researchers tracked sleep, activity levels, melatonin rhythms and depression symptoms of 68 SAD patients who took either low doses of melatonin or a placebo in the morning or afternoon for a winter month when they were most symptomatic. They had determined from healthy subjects that a person's rhythms are synchronized when the interval between the time the pineal gland begins secreting melatonin and the middle of sleep is about 6 hours.

Seventy-one percent of the SAD patients had intervals shorter than 6 hours, indicating that their rhythms were delayed due to the later winter dawn. Taking melatonin capsules in the afternoon lengthened their intervals, bringing their rhythms back toward normal. The closer their intervals approached the ideal 6 hours, the more their mood improved on depression rating scales, supporting the hypothesized link between out-of-sync rhythms and SAD.

"SAD may be the first psychiatric disorder in which a physiological marker correlates with symptom severity before, and in the course of, treatment in the same patients," explained Lewy, referring to patients' rhythm shifts towards the 6 hour interval in response to melatonin.

Taking melatonin at the correct time of day — afternoon for patients with short intervals and morning for the 29 percent of patients with long intervals — more than doubled their improvement in depression scores, compared to taking a placebo or the hormone at the incorrect time. While the study was not designed to test the efficacy of melatonin treatment, the researchers suggest that its clinical benefit "appears to be substantial, although not as robust as light treatment." They propose that the 6-hour interval index may be useful for analyzing the circadian components of non-seasonal depression and other sleep and psychiatric disorders.

Also participating in the study were: Bryan Lefler, Jonathan Emens, Oregon Health and Science University, and Vance Bauer, Kaiser Permanente Northwest Center for Health Research.

Lewy AJ, Lefler BJ, Emens JS, Bauer VK. The circadian basis of winter depression.  Proc Natl Acad Sci U S A. 2006 Apr 28.