A few years ago, researchers thought that seasonal affective disorder (SAD)
was simply due to the shorter days of winter. Then they realized that SAD
probably has a circadian (24-hour) rhythm component as well. In other words,
bright-light therapy is known to shift people's biological clocks, and also
known to counter SAD depression. So it seemed plausible that people with SAD
become depressed in winter because the later dawn shifts their biological
clocks later with respect to real time and their sleep/wake cycles.
But now it looks as though not all people with SAD have tardy biological
clocks, a new study suggests. In fact, it may be that a few have biological
clocks that tick too fast.
The investigation was headed by Alfred Lewy, M.D., Ph.D., vice chair of
psychiatry at Oregon Health and Science University. Results were published in
the May 9 Proceedings of the National Academy of Sciences.
Lewy and his colleagues selected 68 individuals diagnosed with SAD to
participate in their double-blind, placebo-controlled, three-week winter
trial. The subjects were randomly placed in one of three groups. A group of 22
subjects were given low-dose melatonin capsules each afternoon for three weeks
to advance their biological clocks because giving a small dose of exogenous
melatonin in the afternoon, when the body does not normally produce melatonin,
is known to advance the clock. In fact, the afternoon melatonin served as a
proxy for morning light therapy since the latter is difficult to study in
double-blind, placebo-controlled trials.
Another group of 22 subjects were given low-dose melatonin capsules each
morning for three weeks to delay their biological clocks. In short, the
morning melatonin served as a proxy for evening light therapy.
The remaining 24 of the 68 subjects served as controls. Each day they
received capsules of a placebo, instead of melatonin, during the three weeks
All subjects were assessed for levels of depression at both the start and
end of the study. The scientists then compared depression outcomes for the
Seventeen of the subjects—11 from the first group and six from the
second—experienced a substantially greater reduction in depression than
the placebo group did (34 percent versus 14 percent). However, the remaining
27 subjects in the two active groups did not. Why the 17 subjects showed a
substantial reduction in depression while the 27 subjects did not was because
the improved group had received the correct treatment for their body clocks
(afternoon melatonin for the prototypical phase-delayed subjects and morning
melatonin for the atypical phase-advanced subjects), according to the
So there seem to be two types of SAD patients, Lewy and his team concluded.
The biological clocks of most shift later in winter, so they will respond to
morning light treatment. A minority, however, may have biological clocks that
shift earlier in winter, so they will respond to evening light treatment.
"The old thinking was that [the cause of SAD] was the shorter
day," said lewy in an interview. "The new thinking is that it is
either the later dawn or the earlier dusk."
These findings also have a practical implication, Lewy pointed out. A test
to determine which SAD patients have slow clocks, and thus would respond to
morning light therapy, and which SAD patients have fast clocks, and thus would
respond to evening light therapy, is available only for research purposes.
However, it may become clinically available in a year or two.
Now that SAD seems to show a strong biological-clock component, it is time
to see whether there might also be a circadian-misalignment component to
nonseasonal depression, Lewy asserted. Its role may be minor, he said, but"
even if the role is small, it is so easy to treat. You can give light
to just about anybody. It is extremely safe."
The study was funded by the Public Health Service and the National Alliance
for Research on Schizophrenia and Depression.
An abstract of "The Circadian Basis of Winter
Depression" is posted at<www.pnas.org/cgi/content/abstract/103/19/7414>.▪