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    Mary's Brain vs. Harry's Brain

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

    Genes at Play continued...

    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.

    Liberated From What?

    Some researchers are convinced, however, that when women's roles in society improved, their odds of depression decreased.

    While genetics may play some role, women's self-confidence and self-esteem are at the heart of depression, says Ronald C. Kessler, PhD, professor of health care policy at Harvard Medical School and author of several major depression studies.

    In the 1950s and 1960s, studies showed that women had three times the rate of clinical depression as men. Since then, that number has steadily decreased -- today's women have 1.7 times the rate of depression, he tells WebMD.

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