The glucocorticoid receptor: part of the solution or part of the problem?

Abstract

Clinical studies have demonstrated hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis and increased levels of cortisol in patients with major depression, because of an impairment of glucocorticoid receptor (GR)-mediated negative feedback (glucocorticoid resistance). Moreover, clinical and experimental studies have shown that antidepressants increase GR function, thus leading to resolution of glucocorticoid resistance. Interestingly, a number of studies have also demonstrated that manipulating GR function with both agonists and antagonists has an antidepressant effect, and indeed that other drugs targeting the HPA axis and cortisol secretion - even drugs with opposite effects on the HPA axis - have antidepressant effects. These studies do not support the notion that cortisol has 'negative' effects on the brain. On the contrary, this paper concludes that a lack of the 'positive' effects of cortisol on the brain, because of glucocorticoid resistance, is likely to be involved in the pathogenesis of depression.

• Authors: Carmine M Pariante
• Journal: Journal of psychopharmacology (Oxford, England) (J Psychopharmacol) Vol. 20 Issue 4 Suppl Pg. 79-84 (Jul 2006) ISSN: 0269-8811 [Print] United States
• PMID: 16785275 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Antidepressive Agents
• Receptors, Glucocorticoid
• Hydrocortisone

Topics

• Animals
• Antidepressive Agents (administration & dosage, therapeutic use)
• Clinical Trials as Topic
• Depression (metabolism, physiopathology, prevention & control)
• Humans
• Hydrocortisone (metabolism)
• Hypothalamo-Hypophyseal System (drug effects, physiology)
• Pituitary-Adrenal System (drug effects, physiology)
• Receptors, Glucocorticoid (agonists, antagonists & inhibitors, physiology)