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Fighting Depression By Readjusting the Clock

Many of us feel less energetic in winter, but for some the coming of winter signals the beginning of severe depression. A connection between winter depression (also referred to as seasonal affective disorder, or SAD) and a person's internal 24-hour clock has been suspected for many years. Two recent studies suggest that manipulating the internal circadian timing system of people with SAD so that it tricks them into thinking it is summer rather than winter will relieve depression.

In animals, the length of melatonin production during the night alerts the nervous system to the time of year. Daylight entering the retina sends signals to the body clock cells in the suprachiasmatic nucleus (SCN), which in turn program the duration of melatonin secretion. As daylight decreases and nights grow longer, the duration of melatonin secretion increases. At least in animals, longer melatonin secretion puts the brain and body into a winter state. Two recent studies suggest that the same might be true for people with SAD and that shortening the length of melatonin secretion in winter with bright light will reverse symptoms of the disorder.

For people with SAD being in a winter state means sleeping more; feeling less aggressive, less active, and less interested in sex; gaining weight and craving carbohydrates; and feeling depressed. It may be that a long time ago, it was advantageous for humans to slow down in winter months, as most animals do, and that as the world became more dependent on electricity and people's schedules become more demanding, people had to adapt their rhythms accordingly.

The discovery that human melatonin production can be suppressed by bright light led to the initial test of bright light as a treatment for SAD in the early 1980s. Three large-scale studies published in 1998 conclusively proved that light therapy is effective in treating symptoms of SAD and that morning treatment is more effective than evening treatment. However, the actual effect did not seem to be that significant over that of a placebo.

Most studies testing a new drug or medical intervention compare its effects to those of a placebo. For example, if a new headache medicine is tested, one group of patients will receive the actual drug and another group an inert sugar pill. Neither doctors nor patients know which is which, and both groups of patients have equal expectations of getting better as a result of the treatment. The positive expectations often result in patients experiencing an improvement in their symptoms even if they are only given the sugar pill. This effect is especially true when dealing with antidepressants. Scientists investigating the effects of bright light treatment on SAD have used as controls dim light, light given at a different time of day, or exposure to negative ions (rather than light). In past experiments, including the three studies conducted in 1998, the so-called placebo effect was significant, making in turn difficult to measure how effective the actual treatment was.

In the January 15, 2001, issue of Archives of General Psychiatry, Dr. Michael Terman of Columbia University's College of Physicians and Surgeons and the New York State Psychiatric Institute reported that if light therapy is timed to match an individual's circadian rhythm, the treatment is two and a half times as effective as light given later in the morning or in the evening. Terman and colleagues monitored the melatonin levels of 42 patients with SAD who were receiving light therapy. Thirty minutes of intense, bright light given at an early circadian time (between 7.5 and 9.5 hours after melatonin onset in the evening) meant that people would have an 80 percent chance of getting better. In contrast, later morning light (9.5 to 11 hours after melatonin onset) gave a 38 percent response rate. According to Terman, since neither patients nor investigators had any knowledge of the circadian time interval at the time of treatment, the result can be interpreted as the active treatment having a large effect compared to the placebo.

Terman's study is the first direct proof that a defect in circadian timing might be involved in SAD. A clue as to what that defect might be comes from studies by Tom Wehr at the National Institutes of Health in Bethesda, Maryland. Wehr's group compared the melatonin profiles of 55 adults with SAD and 55 healthy individuals. They were brought into the laboratory for one day in the winter and one day in the summer. Blood samples were taken every 20 minutes for 24 hours while both groups were kept in constant darkness. The scientists found that people with SAD had a longer period of melatonin secretion in the winter than in the summer. In contrast, healthy people had no difference in the length of melatonin secretion between winter and summer. While the time of onset of melatonin secretion was the same in the two groups, the difference was in the time when secretion ended in the morning.

Dr. Wehr interprets these results to mean that people with SAD are detecting and responding primarily to changes in natural light (the light from the sun). In contrast, healthy individuals are perceiving artificial light in homes and offices, which does not differ in intensity or duration between winter and summer, and the artificial light somehow masks the natural light.

Another important finding is that people with SAD and healthy individuals seem to respond differently to changes in melatonin production . According to Wehr, a winter melatonin signal can be induced in healthy people by using artificial lights. However, although the melatonin profiles shift to resemble those of people suffering from SAD in the winter months, healthy individuals still do not experience symptoms of SAD. So SAD people differ not only in the way in which they perceive natural and artificial light but also in the way they then translate the signals from the light into behavior.