Sarah Goodwin

Kathi Ovnic
Holly Korschun
September 15, 1998



The chemical means by which childhood trauma can cause changes in brain chemicals associated with adult clinical depression (particularly in persons with family histories of depression) can be explained by the Stress-Diathesis Model of Mood Disorders, according to Emory University's Charles B. Nemeroff, M.D., Ph.D., who describes the hypothesis in his comprehensive review of depression in the June issue of Scientific American.

The hypothesis, so named "in recognition of the interaction between experience (stress) and inborn predisposition (diathesis)," is based on the body of laboratory research conducted largely at Emory that shows how early traumatic experiences that repeatedly trigger the body's "fight or flight" stress response can lead to permanent changes in brain chemistry. The hypothesis has been confirmed in studies of rats conducted by Emory's Paul M. Plotsky, Ph.D. Preliminary studies in primates appear to corroborate the hypothesis, according to the researchers.

"My colleagues and I propose that early abuse or neglect not only activates the stress response but induces persistently increased activity in CRF (corticotropin-releasing factor)-containing neurons, which are known to be stress responsive and to be overactive in depressed people," says Dr. Nemeroff in the Scientific American paper.

"If the hyperactivity of neurons of children persisted through adulthood, these supersensitive cells would react vigorously even to mild stressors.

"This effect in people already innately predisposed to depression could then produce both the neuroendocrine and behavioral responses characteristic of this disorder," says Dr. Nemeroff, who is Reunette W. Harris Professor and chairman of the department of Psychiatry and Behavioral Sciences at the Emory University School of Medicine.

"In an exciting preliminary finding, Plotsky has observed that treatment with one of the selective serotonin reuptake inhibitors (Paxil) returns CRF neuronal anatomy to normal, compensates for any increase in adrenocortical capacity (as indicated by normal corticosterone production {the hypothalamic-pituitary-adrenal or HPA axis hormonally manages the body's response to stress}) and normalizes behavior (for instance, the rats become less fearful)," says Dr. Nemeroff in referring to the paper.

"We do not know exactly how chronic inhibition of serotonin reuptake leads to normalization of HPA axis activity. Even so, the finding implies that serotonin reuptake inhibitors might be particularly helpful in depressed patients with a history of childhood trauma. Plotsky further reports that all the HPA-axis and CRF abnormalities returned when treatment stopped, a hint that pharmaceutical therapy in analogous human patients might have to be continued indefinitely to block recurrences of depression."

In the paper,Dr. Nemeroff says, "The rat and monkey data raise profound clinical and public health questions. In the U.S. alone in 1995, more than three million children were reportedly abused or neglected, and at least a million of those reports were verified. If the effects in human beings resemble those of the animals, the findings imply that abuse or neglect may produce permanent changes in the developing brain ­ changes that chronically boost the output of, and responsiveness to, CRF, and therefore increase the victims' lifelong vulnerability to depression."


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