GLUCOCORTICOIDS AND THE GENESIS OF DEPRESSIVE-ILLNESS - A PSYCHOBIOLOGICAL MODEL

Abnormalities in the hypothalamic-pituitary-adrenal axis (HPA) have be en the most consistently demonstrated biological markers in depressive illness. Numerous other neuroendocrine disturbances have also been de scribed, including blunted clonidine-induced growth hormone release an d blunted fenfluramine-induced prolactin release. These disturbances a re generally interpreted in terms of monoaminergic receptor dysfunctio n. The theory presented here suggests that chronic stress which activa tes the HPA will in certain susceptible people produce changes in cent ral monoamines. The high level of glucocorticoid receptors on such cen tral neurons is postulated as mediating the alterations. Thus monoamin e abnormalities, rather than being a core aetiological feature of depr ession, are seen as secondary to HPA overdrive.