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

by
Pariante CM.
Stress, Psychiatry and Immunology Laboratory (SPI-Lab),
Section of Clinical Neuropharmacology,
Division of Psychological Medicine,
Institute of Psychiatry,
King's College London, London, UK.
J Psychopharmacol. 2006 Jul;20(4 Suppl):79-84.


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.
CRF
LHPA
Stress
HPA Axis
Astressin
Metyrapone
Ketoconazole
Cortisol blues
Corticosteroids
Mineralocorticoids
Pharmacogenetics
Cushing's Syndrome
CRH1 receptor antagonists
Stress, depression and anxiety
Are antidepressants neuroprotective?
The corticosteroid hypothesis of depression
Glucocorticoid receptors and mood disorders
Stress, dynorphin, dysphoria and the kappa opioid system


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