How to measure glucocorticoid receptor's sensitivity in patients with stress-related psychiatric disorders

Abstract

Stress is a state of derailed homeostasis and a main environmental risk factor for psychiatric diseases. Chronic or uncontrollable stress may lead to a dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, which is a common feature of stress-related psychiatric disorders. One of the key mechanisms underlying a disturbed HPA axis is an impaired function of the glucocorticoid receptor (GR) with an enhanced or reduced feedback sensitivity for glucocorticoids and subsequently altered concentrations of peripheral cortisol. GR function is regulated by a multiprotein complex including the different expression of the hsp90 co-chaperone FK 506 binding protein 51 (FKBP5) that may be genetically determined or acquired in response to stressful stimuli. Specific patterns of a dysregulation of the HPA axis and GR function are found in different stress-related psychiatric entities e.g. major depression, job-related exhaustion or posttraumatic stress disorder. GR challenge tests like the dexamethasone-suppression test (DST), the dexamethasone-corticotropin-releasing hormone (dex-CRH) test or most recently the analysis of the dexamethasone-induced gene expression are employed to sensitively measure HPA axis activity in these disorders. They provide information for a stratification of phenotypic similar but neurobiological diverse psychiatric disorders. In this review we present a synopsis of GR challenge tests with a focus on the application of the DST, the CRH test and the dex-CRH test as well as the dexamethasone-induced gene expression in stress-related psychiatric entities.

Keywords: DST; Dex-CRH test; Dexamethasone; FKBP5; Gene expression; Glucocorticoid receptor; HPA axis; Hypothalamic-pituitary-adrenal axis; Major depression.