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Involvement and role of antidepressant drugs of the hypothalamic-pituitary-adrenal axis and glucocorticoid receptor function.
Neuro Endocrinol Lett 2009; 30(1):11-6NE

Abstract

Changes in the hypothalamic-pituitary-adrenal (HPA) axis are characteristic of major depression. Because the effects of glucocorticoids are mediated by intracellular receptors including, most notably, the glucocorticoid receptor (GR), several studies have examined the number and/or function of GR's in depressed patients. Review scientific evidences have consistently demonstrated that GR function is impaired in major depression, resulting in reduced GR-mediated negative feedback on the HPA axis and increased production and secretion of corticotropin-releasing hormone (CRH) in various brain regions postulated to be involved in the causality of major depression. Hyperactivity of HPA axis is the main biochemical change, besides disturbed monoaminergic neurotransmission, observed in the patients suffering from a major depression. High incidence of depression in Cushing's syndrome as well as antidepressant effects of adrenocortical enzyme inhibitors in major depression support hypothesis that hyperactivity of HPA axis may be involved in pathogenesis of depression. Major alterations of the HPA axis that can be reversed by successful antidepressant therapy are often seen in depressed patients. A possible explanation for this is that the antidepressant-induced increase in GR's renders the HPA axis more sensitive to glucocorticoid feedback. This new insight into antidepressant drug action suggests a novel approach to the development of antidepressant drugs.

Authors+Show Affiliations

Department of Psychiatry and Psychotherapy, Klinikum Fulda gAG, Pacelliallee 4, 36043 Fulda, Germany. georg.nikisch@klinikum-fulda.de

Pub Type(s)

Evaluation Study
Journal Article
Review

Language

eng

PubMed ID

19300389

Citation

Nikisch, Georg. "Involvement and Role of Antidepressant Drugs of the Hypothalamic-pituitary-adrenal Axis and Glucocorticoid Receptor Function." Neuro Endocrinology Letters, vol. 30, no. 1, 2009, pp. 11-6.
Nikisch G. Involvement and role of antidepressant drugs of the hypothalamic-pituitary-adrenal axis and glucocorticoid receptor function. Neuro Endocrinol Lett. 2009;30(1):11-6.
Nikisch, G. (2009). Involvement and role of antidepressant drugs of the hypothalamic-pituitary-adrenal axis and glucocorticoid receptor function. Neuro Endocrinology Letters, 30(1), pp. 11-6.
Nikisch G. Involvement and Role of Antidepressant Drugs of the Hypothalamic-pituitary-adrenal Axis and Glucocorticoid Receptor Function. Neuro Endocrinol Lett. 2009;30(1):11-6. PubMed PMID: 19300389.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Involvement and role of antidepressant drugs of the hypothalamic-pituitary-adrenal axis and glucocorticoid receptor function. A1 - Nikisch,Georg, PY - 2008/08/10/received PY - 2008/12/06/accepted PY - 2009/3/21/entrez PY - 2009/3/21/pubmed PY - 2009/7/2/medline SP - 11 EP - 6 JF - Neuro endocrinology letters JO - Neuro Endocrinol. Lett. VL - 30 IS - 1 N2 - Changes in the hypothalamic-pituitary-adrenal (HPA) axis are characteristic of major depression. Because the effects of glucocorticoids are mediated by intracellular receptors including, most notably, the glucocorticoid receptor (GR), several studies have examined the number and/or function of GR's in depressed patients. Review scientific evidences have consistently demonstrated that GR function is impaired in major depression, resulting in reduced GR-mediated negative feedback on the HPA axis and increased production and secretion of corticotropin-releasing hormone (CRH) in various brain regions postulated to be involved in the causality of major depression. Hyperactivity of HPA axis is the main biochemical change, besides disturbed monoaminergic neurotransmission, observed in the patients suffering from a major depression. High incidence of depression in Cushing's syndrome as well as antidepressant effects of adrenocortical enzyme inhibitors in major depression support hypothesis that hyperactivity of HPA axis may be involved in pathogenesis of depression. Major alterations of the HPA axis that can be reversed by successful antidepressant therapy are often seen in depressed patients. A possible explanation for this is that the antidepressant-induced increase in GR's renders the HPA axis more sensitive to glucocorticoid feedback. This new insight into antidepressant drug action suggests a novel approach to the development of antidepressant drugs. SN - 0172-780X UR - https://www.unboundmedicine.com/medline/citation/19300389/Involvement_and_role_of_antidepressant_drugs_of_the_hypothalamic_pituitary_adrenal_axis_and_glucocorticoid_receptor_function_ L2 - https://medlineplus.gov/antidepressants.html DB - PRIME DP - Unbound Medicine ER -