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February 14, 2003


Women Abused as Children Show Elevated Hormonal Responses to Stress That May Add to risk of Adult Psychiatric Disorders

DENVER -- Women who were sexually or physically abused as children show significantly elevated hormonal responses to stress compared to women with no history of childhood abuse, according to a study by researchers at the Emory University Conte Center for the Neuroscience of Mental Disorders, which is funded by the National Institute of Mental Health and led by Charles B. Nemeroff, M.D., Ph.D. Dr. Nemeroff presented his findings on Feb. 14 in a symposium at the American Association for the Advancement of Science (AAAS) annual meeting in Denver.

The study's findings, previously reported in the August 2000 issue of the Journal of the American Medical Association, suggest that childhood abuse is associated with persistent sensitization or hyperactivity of the pituitary-adrenal and autonomic stress response, which in turn may contribute to greater vulnerability to psychiatric disorders in adulthood.

The findings support the hypothesis that aberrant brain chemistry produced by adverse early-life experiences plays a major role in the later development of mood and anxiety disorders. This hypothesis, the Stress-Diathesis Model of Mood Disorders, was put forth several years ago by Dr. Nemeroff and his colleagues. Dr. Nemeroff is the chair of the Department of Psychiatry and Behavioral Sciences at the Emory University School of Medicine and the study's principal investigator. The study's lead author is Christine Heim, Ph.D.

"Essentially, we're trying to understand the biological basis behind the risk for developing psychiatric disorders in adulthood," Dr. Nemeroff explained.

In the study, 49 adult female subjects, aged 18-45 years, were divided into four groups: those who were sexually or physically abused as children and were diagnosed with depression in adulthood; those who were abused in childhood but had not experienced depression; depressed women who did not suffer child abuse; and a control group with no history of childhood abuse or depression.

"We sought to distinguish the effects of depression versus the effects of early childhood trauma on the stress hormonal systems," said Dr. Nemeroff

All of the subjects underwent the Trier social stress test, named after the University of Trier, where it was developed. The test involved 10 minutes of public speaking and a tricky mental math exercise, performed before a panel of poker-faced observers who purposely did not evince any supportive expressions or gestures.

During the test the subjects' stress hormonal responses were measured via blood samples taken through an intravenous catheter. The catheter was inserted two hours before the stress test to avoid incurring any needle sticks during the actual test performance.

The hormones measured were cortisol and ACTH, or adrenocorticotropic hormone, members of the hypothalamic-pituitary-adrenal axis, both of which are stimulated by corticotropin-releasing factor (CRF). Increased concentrations of cortisol and ACTH are indicative of hyperactive or sensitized CRF systems; the latter have been strongly implicated in mediating the relationship between early-life stress and adulthood development of depression and anxiety disorders.

The researchers found that both groups of women who were abused as children showed exaggerated stress hormonal responses. The effect was especially pronounced in women who were abused s children and who had current major depression: these subjects' ACTH responses were more than six times those of control group members who were comparable in age.

The women who were depressed but had not experienced child abuse showed hormonal responses similar to those in the control group.

Previous research by others has shown that adults who were abused as children may be at greater risk of developing anxiety disorders, including post-traumatic stress disorder, and depression.

In an ongoing follow-up study, the researchers are evaluating the effectiveness of antidepressant medication aimed at blocking the action of CRF within the brain, so-called CRF receptor antagonists. Researchers hope to lean whether such novel drugs could not only treat, but also prevent adult psychiatric disorders associated with early-life stress.

"If we find that this is the case, antidepressants potentially cold have prophylactic benefit," Dr. Nemeroff said.

Other Emory researchers involved in the study are D. Jeffrey Newport, M.D., Stacey Heit, M.D., Yolanda P. Graham, M.D., Molly Wilcox, B.A., Robert Bonsall, Ph.D. and Andrew H. Miller, M.D.

Dr. Nemeroff, who also is the Reunette W. Harris Professor of Psychiatry and Behavioral Sciences, specializes in researching the biological basis of major neuropsychiatric disorders, including mood disorders, schizophrenia and anxiety disorders. In June 1998, he published an article in Scientific American presenting the Stress-Diathesis hypothesis.

This hypothesis became the basis for a five-year $13 million grant awarded in 1999 by the National Institute of Mental Health (NIMH) of the National Institutes of Health. The grant supported the establishment of the Emory Conte Center for the Neuroscience of Mental Disorders, which involves a large team of neuroscientists from Emory, Yale and Princeton, led by Dr. Nemeroff.

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