Future therapeutic targets in mood disorders: the glucocorticoid receptor.

Abstract

The hypercortisolaemia and dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis associated with mood disorders have been attributed to a breakdown in the glucocorticoid-receptor-mediated negative feedback mechanism regulating HPA activity. Reinstating normal feedback may be therapeutic in mood disorders. To review the evidence for the involvement of the glucocorticoid receptor in the pathogenesis and treatment of mood disorders. Medline and hand searches were carried out, selecting literature relevant to psychiatrists and psychopharmacologists. A dysfunction in glucocorticoid receptors is integral to the HPA abnormalities of mood disorders. Antidepressant and mood-stabilising drugs can up-regulate glucocorticoid receptors, restoring glucocorticoid function. Preliminary clinical studies targeting the glucocorticoid receptor are encouraging. Drugs designed specifically to up-regulate glucocorticoid receptors may be integral to future strategies in treating mood disorders.