September 28, 1998
Volume 51, No. 6
Model created for childhood trauma-adult depression link
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 Charles Nemeroff , Reunette W. Harris Professor and chairman of the Department of Psychiatry and Behavioral Sciences at the School of Medicine. Nemeroff described 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 Paul Plotsky, SmithKline Beecham Professor of Psychiatry and Behavioral Sciences. Preliminary studies in primates appear to corroborate the hypothesis, the researchers said.
"My colleagues and I propose that early abuse or neglect not only activates the stress response but induces persistently increased activity in [corticotropin-releasing factor]-containing neurons (CRF), which are known to be stress responsive and to be overactive in depressed people," Nemeroff said 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," he added. "This effect in people already innately predisposed to depression could then produce both the neuroendocrine and behavioral responses characteristic of this disorder."
In a parallel preliminary finding, Plotsky observed that treatment with selective serotonin reuptake inhibitors such as Paxil returns CRF neuronal anatomy to normal, compensates for any increase in corticosterone production (which manages the body's response to stress) and normalizes behavior. "For instance, the rats become less fearful," Nemeroff said.
"We do not know exactly how chronic inhibition of serotonin reuptake leads to normalization of HPA axis activity," he said. "Even so, the finding implies that serotonin reuptake inhibitors might be particularly helpful in depressed patients with a history of childhood trauma." Plotsky further reported that all the corticosterone 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, Nemeroff said.
"The rat and monkey data raise profound clinical and public health questions," said Nemeroff. "In the U.S. alone in 1995, more than 3 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."
Nemeroff's paper is available in its entirety on the Scientific American web site at: