11-13 However, (i) Cortisol nonsuppression following DST is not specific for the diagnosis of major depression; and (ii) the sensitivity of the DST in depression is low. Indeed, only 15% to 25% of major depressed patients are nonsuppressors, while the rate of positive DST increases in severe depression (about 40% to 70% ).14 Despite these limitations, the use of DST in psychiatric research still has considerable merit. For example, serial DST monitoring of depressed patients undergoing

drug treatment showed that DST gradually Inhibitors,research,lifescience,medical turned into suppression in treatment responders.15,16 Patients whose DST remained abnormal or who were initially suppressors, but became nonsuppressors during an observation period, had a poorer prognosis.6,17 In addition,

over a long-term follow-up, DST suppressors at baseline have a better outcome than nonsuppressors.18 Although conflicting results on the predictive value of the DST have been reported, it is generally accepted that (i) the presence of an abnormal DST indicates the Inhibitors,research,lifescience,medical need for a biological treatment, while (ii) the initial DST status has no predictive value in the choice of prescription of antidepressants.19 The combined DEX/CRH test After CRH became available for clinical studies, a more sensitive test than the DST was developed: the Inhibitors,research,lifescience,medical combined dexamethasone/corticotropin-releasing hormone test (DEX/CRH test)20 in which dexamethasone-pretreated subjects receive a single dose Inhibitors,research,lifescience,medical of CRH during the afternoon of the next day. In healthy control subjects, owing to the normal inhibiting activity of the glucocorticoid receptors at the pituitary level, CRH administration induces only a small amount of corticotropin (adenocorticotropic hormone [ACTH]) and Cortisol Inhibitors,research,lifescience,medical secretion. In depressed patients, the ACTH/cortisol response to the combined DEX/CRH test is significantly increased compared with controls. This phenomenon suggests an altered glucocorticoid feedback regulation (ie, decreased glucocorticoid receptor

sensitivity), possibly associated with hypothalamic CRH and vasopressin overdrive.21 The combined DEX/CRH test identifies HPA axis dysfunction with high sensitivity in severe major depression (about 80% ).20 Furthermore, DEX/CRH test normalization typically precedes or coincides with – rather than follows – clinical recovery, Histone demethylase and failure to normalize portends poorly for clinical outcome.22 Patients with persistent severe HPA dysregulation are more prone to relapse within 6 months than those with low Cortisol response to the DEX/CRH test at discharge.23 Moreover, early Lenvatinib datasheet improvement (after 1 or 2 weeks of therapy) and beneficial treatment outcome after 6 weeks are associated with a lower HPA system activity.21 Taken together, these studies suggest that lowering HPA activity and clinical response are related.