Future therapeutic targets in mood disorders: the glucocorticoid receptor

Background The hypercortisolaemia and dysfunction of the hypothalamic-pitui tary-adrenal (HPA) axis associated with mood disorders have been attributed to a breakdown in the glucocorticoid receptor-mediated negative feedback m echanism regulating HPA activity. Reinstating normal feedback may be therap eutic in mood disorders. Aims To review the evidence for the involvement of the glucocorticoid recep tor in the pathogenesis and treatment of mood disorders. Method Medline and hand searches were carried out, selecting literature rel evant to psychiatrists and psychopharmacologists. Results A dysfunction in glucocorticoid receptors is integral to the HPA ab normalities of mood disorders. Antidepressant and mood-stabilising drugs ca n up-regulate glucocorticoid receptors, restoring glucocorticoid function. Preliminary clinical studies targeting the glucocorticoid receptor are enco uraging. Conclusions Drugs designed specifically to up-regulate glucocorticoid recep tors may be integral to future strategies in treating mood disorders. Declaration of interest None.