THE POTENTIAL ROLE OF EXCESSIVE CORTISOL INDUCED BY HPA HYPERFUNCTIONIN THE PATHOGENESIS OF DEPRESSION

Prolonged hypothalamic-pituitary-adrenocortical (HPA) axis overactivit y occurs at all levels of this axis during stress in normals and some depressed patients. This can induce enlargement of the pituitary and a drenals. Various reports showed that cortisol can affect mood and beha vior, and disrupt memory and recall. The integrity of the hippocampus is essential for memory function and, via the high density of its cort isol receptors, cortisol induced inhibitory feedback to the HPA axis. Animal data suggest that over time aging and stress can permanently do wnregulate hippocampal cell receptors, produce chronic hippocampal inf lammation (astroglial), and kill cells. Gushing's syndrome patients (h igh cortisol) show diminished hippocampal size and verbal recall inver sely related to cortisol levels. All the above is consistent with the 'cascade hypothesis' of cortisol induced hippocampal damage with resul tant diminished inhibition to HPA hyperactivity in a circular manner. High cortisol is associated with altered neurotransmitter function, e. g., diminished brain serotonin synthesis, low CSF 5HIAA, and increased noradrenergic activity.