Glucocorticoids and the Genesis of Depressive Illness a Psychobiological Model

Abstract

Abnormalities in the hypothalamic–pituitary–adrenal axis (HPA) have been the most consistently demonstrated biological markers in depressive illness. Numerous other neuroendocrine disturbances have also been described, including blunted clonidine-induced growth hormone release and blunted fenfluramine-induced prolactin release. These disturbances are generally interpreted in terms of monoaminergic receptor dysfunction. The theory presented here suggests that chronic stress which activates the HPA will in certain susceptible people produce changes in central monoamines. The high level of glucocorticoid receptors on such central neurons is postulated as mediating the alterations. Thus monoamine abnormalities, rather than being a core aetiological feature of depression, are seen as secondary to HPA overdrive.