Hypothalamo-Pituitary-Adrenal Axis in Depressive Disorders and Treatment Resistance

Abstract

Background: hypothalamo-pituitary-adrenal (HPA) axis plays an important role in the pathogenesis of depression. Patterns of HPA functioning depend on both biologic factors and psychological background, which, taken together, may increase the risk of depression later on. Objective: to analyze scientific publications on pathophysiology of depression, linked to HPA disruption, assess causal relationship between hypercorticism and depression, role of hypercorticism in clinical symptoms and course of depressive disorder.Material and methods: according to the key words “hypercortiсism”, “depression disorder”, “cortisol”, “treatment resistant depression”, “Cushing’s syndrome”, “Сushing’s disease”, a search was conducted for publications in databases Medline/ PubMed, Scopus, Web of Science, RSCI and other resources.Conclusion: there is a high comorbidity between depressive disorders and HPA axis abnormalities, including endocrine disorders with both increased and decreased cortisol secretion. Hypercorticism related to Сushing’s disease or Cushing’s syndrome is often associated with irreversible mental disorders, especially anxiety and depressive disorders, which persist after normalization of cortisol levels. Depressive patients are characterized by persistently elevated cortisol levels and their non-supression in the 1 mg dexamethasone suppression test (DST); however, sometimes they have reduced cortisol secretion. The possible pathophysiology mechanisms of hypercorticism are discussed. Beside hypercorticism, increased level of adrenocorticotropic hormone (ACTH) and decreased secretion of ACTH after CRH stimulation are demonstrated. It has been demonstrated that elevation of cortisol levels may precede the development of depression and as such can be used as marker of increased depression risk. Hypercorticism in patients with depression may promote its increased severity and transform ation of depressive symptoms. Persistent hypercorticism and non-supression of cortisol in DST are predictors of poor outcomes. HPA dysfunction seems to play an essential role in evolvement of treatment resistant depression. There is data on the efficacy of drugs modifying HPA activity for amelioration of affective disorders and psychotic symptoms in patients with depression. Further research into HPA functioning in patients with depression are needed to clarify pathogenetic mechanisms and development of newer treatment approaches to depression.