Depressed patients show an altered stress hormone regulation and psychopathological symptoms. Researchers at the Max Planck Institute of Psychiatry in Munich, Germany, and the GSF Research Centre, Institute for Mammalian Genetics in Neuherberg generated a stress hormone receptor-deficient mouse exhibiting a blunted stress response and reduced anxiety. This finding, published in Nature Genetics, vol. 19, June 1998, may provide new possibilities of treating depression and anxiety.

The hypothalamus, located at the ventral diencephalon, is a relay station to integrate the central and the autonomic nervous system by regulating the secretion of various hormones into the blood stream. One of the hormones, which is secreted under acute stress conditions in the hypothalamus, is the neuropeptide corticotropin-releasing hormone (CRH). CRH triggers the release of the adrenocorticotropic hormone (ACTH) in the anterior pituitary. Subsequently, ACTH stimulates the release of cortisol from the zona fasciculata of the adrenal cortex.

In patients with severe depression, the stress hormone cortisol is highly elevated in the cerebrospinal fluid and blood plasma causing alterations of various tissues such as the brain and immune system. Under normal stress condition, there is an immediate down-regulation of cortisol via the hypothalamic-pituitary-adrenal (HPA) axis--negative feedback loop--which results in a normal plasma concentration of the stress hormone cortisol. For patients with a depression, and healthy individuals with a genetic pre-disposition for depression, it has been shown that the down-regulation of the stress hormone cortisol is altered. In pharmacological studies, it has been shown that antidepressants are able to down-regulate elevated cortisol levels.

These results indicate that the clinical relevance of antidepressants is the down-regulation of the stress hormone cortisol. Moreover, it has been shown in animal models, in patients with depression, and by
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Contact: Wolfgang Wurst
wurst@mpipsykl.mpg.de
+49-89-30622-639
Max-Planck-Gesellschaft
29-May-1998