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Mary's Brain vs. Harry's Brain

Genetics, brain structure, social roles make women more prone to clinical depression.

Evolution at Work continued...

This makes sense, in terms of how stress affects today's women. "Emotional responses are hardwired in women; we're more sensitive to losses of attachment," Weissman tells WebMD. "That's what depression is about -- loss of attachment. The breakup of a relationship, divorce, separation, or death is a major precipitating event for depression."

Estrogen seems to indirectly set the stage for depression after a stressful event by triggering an intense hormonal response to stress. Research has shown that estrogen increases and prolongs the body's production of cortisol, a stress hormone. Cortisol is thought to play a key role in depression.

One large study of twins showed that -- if there is a family history of depression -- an episode of major stress like divorce could double a woman's risk of developing depression, says Kenneth S. Kendler, MD, a psychiatrist and geneticist at the Medical College of Virginia.

Also, panic attacks (related to depression and anxiety) are more frequent in women over age 50. This is especially true if they had five or more stressful events in one year or if they suffered from depression, reports Jordan W. Smoller, MD, ScD, a psychiatric researcher with Massachusetts General Hospital in Boston.

Genes at Play

Genetics are another critical part of depression. Researchers like to use heart disease risk as an analogy: For people with family history, an unhealthy lifestyle will increase the risk dramatically. If you don't have family history, your body can tolerate more abuse.

Researchers like George Zubenko, MD, PhD, are investigating sex-specific "susceptibility" genes that increase risk for clinical depression.

"There is an enormous amount of literature supporting the fact that major depressive disorder is about twice as high in women as in men," says Zubenko, who is a professor of psychiatry at the University of Pittsburgh Medical School.

His evidence:

  • Twin studies demonstrate that genetic factors typically account for 40% to 70% of the risk for developing depression.
  • Family studies have shown a twofold increased risk among first-degree relatives.
  • Adoption studies have also confirmed an important role for genetic risk factors in the development of depression.

Zubenko's study involved 81 families with recurrent, early-onset (before age 25) major depression. He found that nearly one-half of first-degree relatives suffered from one or more mood disorders - six times the risk of the general population.

He also identified 19 genetic regions that were linked to recurrent, early-onset depression. Sixteen regions were linked to only one sex, and only three were linked to depression in both sexes.

There appear to be more genes that preferentially affect women's risk. The effects of "sex-specific" risk genes may diminish after age 35 to 40, when sex hormone levels begin to fall, he says.

"The number of genes that appear to affect risk in one sex or the other preferentially affect risk in one gender but not both," Zubenko tells WebMD. "And the majority of those sex-specific genes affect women."

The genes that influence risk of depression appear to work together to increase risk - and typically affect a spectrum of depressive disorders as well as alcoholism, he says.

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