The Season of SADness?

One of the most basic facts of life on earth is the daily rhythm of light and dark. As earthly creatures, we come equipped with brains prewired to this rhythm. Our own internal pacemaker tunes our mental and physical energy levels more or less to the cycles of sunlight.

At least that's the general plan. Sometimes the system is a little off and night just won't quit the brain.

As the seasons turn, in response to the waxing and waning of the sun, most people respond to the change in environmental light—a pronounced shortening of the period of light—with a shift in energy. The body seems to slow down, we feel fatigue, we are slow to wake in the dark of the morning—a faint echo of seasonal patterns of response among other animals. In one survey, conducted in the state of Maryland, over 90% of those surveyed reported that they felt some difference in mood, energy or behavior with the change of seasons.

But for some people the change in energy level is so extreme they have trouble functioning. These people—some estimates say 11 million in the U.S.—have seasonal affective disorder (SAD), or winter depression.

SAD is probably as old as patterns of human migration to latitudes distant from the equator. The disorder is rare in those living within 30 degrees of the equator, where daylight hours are long, constant, and extremely bright. But only recently has it become clear how the disorder emerges from seasonal change.

• Research now underway suggests that SAD may come about through the collision of two vulnerabilities—one to depression, the other to seasonality. People with SAD seem to be unique in that they have a kind of "biological calendar;" they generate a distinct biological signal of lengthening nights, and that sets off a cascade of responses resulting in depression.
• Carefully timed exposure to specific types of light early in the morning constitutes the most specific therapeutic approach to SAD now available. But in the near future it may be possible to prevent the disorder before it starts. Research already in progress is testing whether seasonal administration of an antidepressant drug in advance of symptoms can ward them off entirely.

That makes Norman E. Rosenthal, M.D. very happy. Clinical professor of psychiatry at Georgetown University and researcher at the National Institute of Mental Health (NIMH), he coined the term Seasonal Affective Disorder—over two decades ago. "Finally," he says, "pharmaceutical companies are getting interested in SAD. That will help focus public attention on it as a real problem, not just an inconvenience."

After all, he points out, the disorder takes up half the year. The average duration is five months at 39 degrees latitude. "And we're not talking about the Arctic Circle here." But geography counts.

Location, Location, Location

In the United States, the symptoms of SAD usually begin in October or November, are most pronounced in January and February, when days are shortest, and subside in March or April. As the days shorten, those afflicted are drained of energy, sleep excessively (sometimes needing as much as four hours more per day than in summer), crave carbohydrates and overeat, and become increasingly sluggish. Sufferers engage their environment less and withdraw socially; they also lose interest in sex. They feel sad, empty, or anxious.

Such symptoms qualify as SAD only if they resolve in the spring and summer, and mood then returns to normal. And it isn't SAD unless the symptoms recur for two or more consecutive winters.

Generally, the symptoms of SAD are mild to moderate and the condition is more prevalent with distance from the Equator. SAD is up to eight times more common in the northern U.S. and Canada than in Florida. However, regular consumption of fish rich in omega-3 fatty acids may prevent the disorder. Last year researchers reported that northerly countries where fish consumption is high—Iceland and Japan, for example—are spared the expected high rates of seasonal affective disorder.

As with major depression, those most at risk of developing SAD are women in their 20s. And as is common among people subject to depression, more than two thirds of them report at least one close relative with the disorder. In one study, six percent of suffers had such severe symptoms they required hospitalization.

A Matter of Melatonin

The disorder, says research psychiatrist Thomas Wehr, M.D., chief of the Section on Biological Rhythms at NIMH, has its roots in a mechanism that is ubiquitous among animals. Most animals (and plants) detect changes in seasons by registering day length. Production of the hormone melatonin is a chemical signal of that change.

The changes of SAD are so reminiscent of changes in animals' seasonal cycles—changes in sleep, appetite, activity levels, social contact and sex—that "it was only reasonable to investigate whether SAD was governed by that same melatonin mechanism," Dr. Wehr explains. Indeed, he and colleagues reported in the Archives of Psychiatry, patients with SAD register an abnormality in melatonin secretion that healthy controls do not.

Normally, our bodies produce the hormone melatonin while we sleep. Melatonin has a slowing effect on the nervous system and induces sleep, summer and winter.

But uniquely in people with SAD, the period of nightly melatonin secretion is prolonged—and then, only in the winter months. Melatonin production fails to shut off on time. In the summer months people with SAD produce the same amount of melatonin for the same amount of time as healthy controls. But in the winter, melatonin production persists. Healthy controls show no such seasonal change in nightly melatonin production.

A Big Half Hour

The winter-summer difference in melatonin production among SAD sufferers is only 38 minutes long—but that's 38 important minutes. That same amount of prolonged melatonin secretion in winter, says Dr. Wehr, is "sufficient to elicit behavioral changes in other mammals."

While the changes in melatonin secretion occurred only among the SAD-susceptible, we all have the capacity for it. Dr. Wehr found that normal non-SAD volunteers could be pushed into prolonged melatonin secretion after enduring very tightly controlled cycles of exposure to light and dark.

"We all have the capacity to show changes in melatonin secretion, but in the modern environment that response does not occur," says Dr. Wehr. The modern environment, of course, is full of artificial light, and for most people the body reads it as dim daylight well enough for it to impact melatonin production.

"It could be that SAD patients are less sensitive to light. They are not perceiving artificial indoor light as sunlight." And healthy individuals, because they are sensitive to indoor light, do not biologically perceive changes in day length during winter.

In the Dark

"People with SAD are literally in the dark," explains Dr. Rosenthal. "They don't take artificial light seriously biologically. They get a seasonal signal that is not overridden by artificial light" as it is among the non-SAD. "As a result, people with SAD need supplemental light."

Nightly melatonin production takes place in the pineal gland, which gets its orders from an internal pacemaker, a cluster of nerve cells deep in the brain's hypothalamus that registers light conditions and controls rhythms of alertness. The hypothalamus, in turn, gets its information about light and dark via a dedicated nerve pathway, a kind of light superhighway that runs between the retina and the hypothalamus.

Neuroscientists know that the photoreceptors involved in this pathway are special, different from the rods and cones that regulate everyday vision. It may be that genetic variation in these receptors may render some people susceptible to SAD.

Bright light also affects the emotional brain, reports Dr.. Rosenthal. "We now know—it has been recently demonstrated in imaging studies—that bright light of suitable duration affects the parts of the brain known to be involved in mood regulation."

However they get there, it isn't just that SAD-sufferers exhibit a seasonality in melatonin production, says Dr Wehr. They are also susceptible to depression. "If melatonin increases, most normal people do not become depressed. That points to a second difference in those with SAD. They respond to the change in melatonin with other changes."

While we call these changes "depression," the term does not "do justice to the range of changes" people experience, Dr. Wehr insists. The changes affect fundamental bodily functions, shifts that are at least as much physical as psychic—in energy, drive, weight, sexual desire. These are collectively referred to as "reverse vegetative" changes, and point to disturbances far deeper than mood but perceived as mood.

A Whole New Approach

The depression of SAD is unusual in yet another way. Sufferers can predict when it will strike. And that is opening the door to attempts to prevent onset of the disorder.

Trials are now underway of one or more antidepressant drugs in once-a-day formulations started a month before the usual onset of SAD and continued throughout the season of risk. While the results are not in yet, the study is premised on the idea that patients may not need to take the medication all year if they start ahead of time to ward off symptoms. With any luck, the study will demonstrate that they can discontinue medication in the spring and resume it early in the fall.

One drug now under study for such a use is Wellbutrin. Zoloft is another.

Researchers at the National Institutes of Health are also exploring the feasibility of a totally different pharmacologic approach to SAD, administering the beta-blocker propranolol. It acts at the pineal gland to shut off the signal of melatonin production. A single dose in the morning mimics the effect of morning light. Reports Dr. Wehr, "The studies are promising."

"Light will always be an important element in the treatment of SAD," says Dr. Rosenthal. "And it provides an important clue to what is going on in the illness."

But he is optimistic that drugs may play a role in the future. Light therapy is sometimes not sufficient to banish SAD. Or people are not willing to undergo it.

The search for sensible drug therapy for SAD will have other benefits, he believes. "The connection with light is well-known," he observes. "And much research in SAD has been focused on light therapy. But still the condition is neglected."

Dr. Rosenthal thinks that drug therapy will help put SAD on the map, squarely above the thirtieth parallel but definitely somewhere under the sun.