Autumn. Mornings are dark. Dusk comes dishearteningly early. You are feeling more tired, melancholy. The rapidly disappearing daylight seems almost to drag away part of your spirit with it. Should this dip in humor worry you? Not really--youll adjust. Unless you are prone to seasonal affective disorder. For the several million Americans who succumb, the darker half of the year brings a heavy veil of sadness. They become depressed, listless, chronically fatigued, and their mood does not rebound until March, when the daylight extends to early evening.

In general, the farther north one lives on the globe the more common seasonal depression becomes. Below the 30th parallel, which links Jacksonville, Fla., to Houston and the Baja Peninsula south of San Diego, the winter blues are virtually unknown. In sunny Florida, just 1 percent of the population suffers from seasonal affective disorder, appropriately known as SAD, but in New York State the rate is 5 percent. In Alaska, one out of every 10 residents experiences winter mood problems.

Why are some people bowled over, whereas their neighbors simply feel a bit glum? And how can all of us brighten our autumnal outlook? Psychologists and neuroscientists are finding answers. And what they are discovering goes far beyond antidotes for seasonal depression; they are gaining insight into how our environments influence our minds, how our brains control mood and how our internal clocks keep many bodily functions in sync.

Sad yet Hungry

Seasonal depression has been recognized for millennia. The great Greek physician Hippocrates was aware in the fifth century B.C. that mood and energy varied with sunlight. People living in sunnier regions were happier, had a more optimistic outlook and were less often sick, he wrote in his treatise Airs, Waters, Places. Yet it was not until the middle of the 20th century that people began to pay real attention to the condition. And it was not until the 1980s that researchers began to examine winter depression closely. Norman E. Rosenthal and Thomas A. Wehr, then at the National Institute of Mental Health (NIMH), and their colleagues developed diagnostic criteria that allowed them to evaluate symptoms objectively. In 1984 the malady was finally christened seasonal affective disorder.

The classic signs include diminished pleasure in life, a gloomy mood and difficulty concentrating. In the morning, SAD sufferers say they feel good enough, but their liveliness fades with the day's passage. Week by week, as the nights lengthen, these individuals withdraw from social life, lose interest in sex and muster little enthusiasm for anything. They describe themselves as empty.

All these symptoms are common to depression, too. The difference is the seasonal link. SAD always commences at a particular time of year. Some people have symptoms as early as September 1, but the problem is really significant in October and November, explains Siegfried Kasper, a psychiatrist at the Medical University of Vienna in Austria. In spring the problem disappears completely, as if it had never existed. Furthermore, whereas depressives often lie awake at night for hours, SAD people tend to sleep excessively, as much as four hours more a night than in summer. They seldom experience lack of appetite, common in depression, and often have hunger attacks that they satisfy with carbohydrates or sweets, leading to weight gain.

Hormone of the Night

The persistence of SAD is clear, but why would a simple absence of daylight trigger such emotional changes? Is the amount of sunlight even the critical factor? For SAD individuals, spending a long time in a windowless room can set off a depressive episode. The answer lies in how humans detect light. Many animals track the seasons by noting changes in day length. Bats, hamsters and groundhogs use the signal to go into hibernation. Daily and seasonal changes in daylight must somehow be registered by the eyes and calculated by the brain. In the early 1970s a small bundle of neurons was discovered that performed this analysis. The bundle--the size of a grain of rice--is the suprachiasmatic nucleus (SCN), and it is located in the brain's hypothalamus near where the two optic nerves from the eyes cross [see illustration on page 79].

The SCN is our body's master timekeeper, our internal 24-hour clock. If this pinch of cells is removed from rats, many processes driven by normal circadian rhythm collapse, including the animals sleep-wake cycle as well as functions of their heart, intestines and liver. As soon as the first rays of sun at dawn sneak between the eyelids onto the retina, special photoreceptor cells signal the neurons of the SCN to begin firing more rapidly. The SCN maintains this rate all day, like a signaling beacon that doesnt stop. The ringing--via many intermediate steps--suppresses the secretion of melatonin, the so-called sleep hormone, by the pineal gland. An evening rise of melatonin in the bloodstream makes us sleepy, and high levels prevail all night long; during the day, however, the hormone can scarcely be detected.

Melatonin's ebb and flow repeats every day. But the cycle's precise timing and duration varies across the year. In spring and summer the SCN neurons fire for longer each day; shorter signaling occurs during autumn and winter. As a result, the profile of melatonin synthesis differs for each season, and it affects many aspects of animals lives, among them appetite, total daily activity levels, social contact, drive to reproduce and, of course, the need for sleep.

Those daily and seasonal levels of melatonin might hold the key to SAD, Thomas Wehr of the NIMH realized during his work in the 1980s. Wehr wondered whether the daily profile of melatonin production somehow differed for SAD sufferers. After tracking many subjects, Wehr found that the seasonal variation in melatonin secretion was similar for SAD and non-SAD people. But for SAD subjects the nightly melatonin cycle lasted 38 minutes longer in winter.

A 38-minute disparity might seem insignificant, given that daylight on a June day in the U.S. lasts nearly 16 hours and that even on a December day it ekes out a little more than eight hours. But the difference matters tremendously. In hamsters, for example, prolonging melatonin secretion by 30 minutes changes reproductive patterns.

Jet Lag Proves It

Scientists thought the extended melatonin dose was the answer to SAD--after all, as the days lengthen in spring, the melatonin-secretion phase shortens and humans revive their interest in life. But the explanation had a problem: there was no physiological evidence that an additional half an hour of melatonin caused depression. And pharmaceuticals that suppress synthesis of the hormone did not seem to help SAD patients.

Researchers concluded that something more basic must be amiss in how SAD people sense light. Led by Alfred Lewy, head of the Sleep and Mood Disorders Laboratory at the Oregon Health & Science University, scientists in the past decade have devised a more comprehensive theory. In today's world, lit by incandescent, fluorescent and halogen lamps day and night, people have become more or less decoupled from the natural daylight cycle. In the morning, most people's inner clocks seem to register artificial light as weaker than sunlight, yet the rays are still enough of a sign to suppress melatonin secretion. Man-made light also keeps the expected production of melatonin at bay after the sun goes down. As a result, our circadian clocks tick somewhat independently of actual day length and season.

Not so for people with seasonal affective disorder. For SAD patients, the 100 to 500 lux brightness of typical homes is not enough to tell the SCN to halt the pineal gland. In the morning, the gland continues to secrete melatonin--at lower levels than at night but still to a greater degree than the normal near-zero of daytime. And in the evening melatonin rises despite the artificial lights, dampening mood by dinnertime and increasing the likelihood of depression.

Further refinement of this theory has pointed to a phase delay in melatonin secretion as the real culprit. The internal clocks of SAD patients not only go into night mode earlier in the evening and remain in night mode longer in the morning, they lag behind natural daylight time and trail other body rhythms. That our brains cannot readily shrug off such phase shifts is clear to anyone who has ever made a long-distance flight. Immediately after such a trip most people are not just tired but also grumpy and listless--jet lag has them down. After a few days their inner clocks adjust their phase to the new timing of dawn and dusk, and the symptoms disappear. David Avery of the University of Washington, who has studied seasonal depression for years, explains the analogy: People with seasonal depression experience something like constant jet lag. They wake up and feel as if it is the middle of the night. And as several studies have shown, from a physiological point of view it really is the middle of the night for them.

Morning Shower of Light

Knowing the physical cause of SAD has lent credence--and specificity--to one form of therapy that has been gaining in recent years, according to anecdotal reports. In Hippocrates day the remedy of choice was to have sufferers look at the sun, a practice that was somewhat hard on the eyes. Today so-called light boxes do a better job. The boxes, one or two feet on a side, contain special lamps that produce up to 10,000 lux of white light--equivalent to the outdoor light of a bright summer day.

For many patients, 30 to 45 minutes of bright light every day, begun during the dim stretches of autumn and continued throughout winter, improve their mind-sets demonstrably. The timing of the dose is important, however. According to various studies, soaking up the light at noon is worthless, and evening doses are of limited value for improving patient moods. Early-morning applications are far and away the best. Patients must wake up early and sit directly in front of the boxes, typically while having coffee or looking at the day's newspaper. Apparently, the intensive light tells the timekeeping neurons in the suprachiasmatic nucleus that the day has begun, so it is time to end the nocturnal synthesis of melatonin. According to most reports, more than 60 percent of SAD patients respond to the morning showers of light.

Done every day, the regimen also appears to reset the clock so it is in proper phase again with the rest of the body. And that adjustment seems to correct the evening onset of melatonin secretion.

According to current treatment protocols, patients should be seated within one to two feet of the light boxes by 6 A.M. or so. Yet Michael Terman, a psychologist at Columbia University, says this strict regimen may have to be adjusted. For some people, that time is much too early. What's important is not the time of day but the time on each patient's circadian clock--where the person is in his or her daily cycle of melatonin production. By taking blood samples to determine melatonin levels, Terman has found the most effective timing of light treatment for dozens of patients. They seem to benefit most when they sit in front of the lamps about eight hours after their bodies start producing the hormone the evening before.

More Serotonin, Please

More recently, one of the brain's chemical messengers has been implicated as a co-conspirator in the wintertime blues: serotonin. This neurotransmitter affects various aspects of appetite, sleep and, most important, mood. Serotonin plays a decisive role in many types of depression, and increasingly, depressed patients are being treated with drugs that delay the reuptake of serotonin, keeping levels in the blood higher. It turns out that these so-called SSRIs--selective serotonin reuptake inhibitors--also help people with seasonal mood swings.

This correlation suggests that as autumn daylight diminishes, the serotonin levels in SAD sufferers change inappropriately. Various studies have since revealed that most people's serotonin levels reach an annual low point during January and rise with the longer days of spring. But new thinking suggests that falling serotonin levels could conspire to make certain individuals depressed if they have one kind of genetic makeup.

Just like every other gene in our bodies, two copies of the so-called 5-HTTLPR gene exist inside every cell. But the two alleles are not necessarily identical; there is a short version and a long version. In 1998 a research group led by Rosenthal at the NIMH found that people with at least one short allele are more prone to seasonal depression and to more severe symptoms. Multiple studies have found a hereditary pattern, too; in the families of SAD patients, 13 to 17 percent of immediate relatives also suffer from seasonal depression. In the general population, the rate varies from 1.4 to 9.7 percent depending on the distance from the equator.

Genes, changes in levels of important hormones and neurotransmitters, an out-of-sync circadian clock--many factors seem to play a role in seasonal depression. But this disorder makes one thing clear: even in the 21st century, human beings are not independent of nature. Our inner clocks still track the seasons. For all we know, evolution may favor sluggishness in fall and winter as a way to promote physical and psychological renewal. Perhaps the problem is that in today's world such a life in tune with the seasons is no longer possible, and the SAD individuals are trying harder to preserve human nature.