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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.

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