In an article about depression last Thursday, Dr. George P. Chrousos was identified incorrectly as a researcher at the National Institute of Mental Health. He works for the National Institute of Child Health and Human Development.
Researchers exploring the chemistry of depression have found that a recently discovered brain chemical may be central to many of its symptoms, as well as to the eating disorder anorexia nervosa.
The research does not locate the cause of depression, but illuminates the mechanism of the disease and related diseases, showing how they may be related to the basic stress system of the body.
The work was published yesterday in the New England Journal of Medicine by Drs. Philip W. Gold and George P. Chrousos at the National Institute of Mental Health, and offers several new pieces of chemical evidence about depression as well as Cushing's disease and the eating abnormalities anorexia nervosa and bulimia.
Some believe that in depression, the body turns on its "fight or flight" response, but is prevented from turning it off again. This produces constant anxiety and overreaction to stimulation, followed later by the paradoxical response called "learned helplessness" in which victims apparently lose all motivation.
In animals, physical danger and the release of the hormone CRH into the system can raise the heartbeat and blood pressure, stop feeding behavior and sexual behavior and dampen the immune response -- all in preparation for action.
In humans, said Gold, both psychological and physical stress produce similar kinds of response, for which the apparent trigger is CRH, a brain chemical isolated for research only four years ago.
Dr. David Kupfer of the Western Psychiatric Institute in Pittsburgh said the papers "help us get to underlying causes of depression," and show that it is "a brain disease, rather than a psychological dis- ease . . . "
With this work and others homing in on CRH and the place in the brain where it is produced, "we're in the right house, the right area. Now we just need to find the front door," Kupfer said.
The papers show similarities between diseases that formerly have been separated into distinct categories, psychiatric and medical.
In depression, anorexia nervosa (obsessive avoidance of food) and Cushing's disease (a disorder of the adrenal cortex characterized by obesity and hypertension), doctors have noted similar stress symptoms, especially high levels of cortisol -- a byproduct of released CRH -- in their patients.
Gold and Chrousos found that depression and anorexia show strong chemical similarities, with patients showing high levels of CRH in their systems in both cases. In addition, the families of anorexic patients often have histories of depression.
The researchers also found that the defect producing abnormal levels of CRH and other chemicals must be located in the hypothalamus and adjacent regions of the brain, rather than other previously suspected areas.
At the same time, the researchers showed that bulimia, a disorder in which patients eat excessively and then force themselves to vomit, can no longer be seen as related to anorexia. Levels of CRH in bulimia were found to be normal.
Perhaps more important for medicine, the researchers found that Cushing's disease and depression, which have virtually identical symptoms at their early stages, are quite different and can be distinguished chemically by testing for CRH-related functioning. Cushing's disease -- which resembles depression at first but later produces symptoms such as a puffy "moon face" and large fat deposits in the legs or in a hump on the back -- can be treated in early stages by surgery on the pituitary.