Puberty changes a lot more than the way kids look and act. It sets in motion a tendency to depression among females.

No matter how the numbers are counted, women are twice as likely as men to be diagnosed with unipolar major depression: 21.3% of women and 12.7% of men experience at least one bout of major depression over the course of their lifetime.

However, once depression occurs, the clinical course is identical. Men and women experience similar duration of depressive episodes-and equal likelihood that depression will recur.

It’s the same around the world, and it’s specific to unipolar depression. Men and women suffer in equal number from bipolar, or manic, disorder.

The gender difference in susceptibility to depression emerges at age 13. Before then, young boys are, if anything, a bit more likely to be depressed than young girls.

And there’s some evidence the gender difference winds down four decades later. In other words, major depression is most commonly a disorder of women in the childbearing years. Just why this is so is a matter of hot debate.

It’s hormones, insists Adrian Angold, M.D., associate professor of psychiatry and behavioral sciences at Duke University. He indicts not only estrogen but testosterone, both of which rise in women during puberty. Testosterone is easily converted to estrogen, which then acts on the brain.

But it’s not the hormones alone, otherwise all females would get depressed. His evidence suggests that estrogen switches on some inherited vulnerability to depression, perhaps a deficiency in serotonin.

Estrogen is known to modulate neurotransmitters, certainly serotonin. “In the later stages of puberty, when estrogen and testosterone rise to a certain level, this switches on some genetic effect on depression that was not apparent before,” says Angold. “This increases the propensity to become depressed under any circumstances.”

Depression is just waiting in the wings. But whether someone gets depressed then depends on happenstance. In his studies, girls who experience stressful life events are three times more likely to get depressed than those who do not. One stressor has a big impact on precipitating depression in pubertal girls-having a mother either with a history of mental illness or currently experiencing depression.

And that takes Angold right back to genetic vulnerability. “What we think of as environmental also runs in families.” From studies of boy-girl twin pairs, psychiatrist Kenneth S. Kendler, M.D., of Virginia Commonwealth University, contends that whatever genes contribute to depression, they are to some degree different in men and women. Nor is there a single set of genes that is expressed as depression in women and alcoholism in men. “Otherwise you’d expect depression in a sister to be strongly correlated with alcoholism in her brother; we didn’t find that,” says Kendler.

Yes, the hormonal fluctuations girls experience in their monthly menstrual cycles create a mood response by turning genes on and off. But that doesn’t account for all depression, Kendler finds.

Environmental factors are also important. He highlights one event that contributes strongly to gender differences in depression-childhood sexual abuse involving attempted intercourse. “It’s a pretty potent risk factor.”

Not only do girls experience abuse more than boys but the abuse is more toxic to them. Other studies show that early sexual abuse in girls can create long-term hyperactivity of the stress hormone system so that they overrespond to stress in adulthood.

One strong stress of a threatening kind can not only bring on a depressive episode but it can permanently change the brain-“kindle” it. It then takes less and less stress to set off bouts of depression.

Then, too, Kendler adds, “socialization factors are likely to play a role. There must be something in rearing patterns in which girls are reinforced for expressing emotions and boys are teased for that.”

The emotional coping styles of males and females are radically different, offers psychologist Susan Nolen-Hoeksema, Ph.D., of the University of Michigan. “Men avoid negative emotions. Women don’t.” Unfortunately, women can get stuck in such emotions, caught in a cycle of passivity and despair.

Her work shows that women are more likely to ruminate about the stressors they encounter. They focus on symptoms of distress and the possible causes and consequences of the symptoms in a repetitive and passive manner.

Some rumination is natural. But people who ruminate a lot amplify negative events.

They generate more negative memories from the past, are more pessimistic about the present and more fatalistic about the future. That makes them increasingly hopeless, distorts their thinking, and renders them less likely to take positive action.

But wait-it gets worse. Their hopelessness makes them unpleasant to be around-and thus unlikely to get needed social support from relationships they are in.

The negative response in turn makes it harder for the body to handle subsequent stressors of any kind. And early adolescence provides challenges aplenty for girls, says Nolen-Hoeksema-from a surge in sexual abuse to new attunement to the needs of others to new awareness of limitations imposed on them by societal gender roles.

It is possible to short-circuit depression by curbing the tendency to ruminate. Studies show that cognitive therapy and mindfulness meditation are effective in helping people overcome rumination.