Innovative Approaches for the Treatment of Depression: Targeting the HPA Axis |
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Authors: | Fiona Thomson Mark Craighead |
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Institution: | (1) Department of Molecular Pharmacology, Organon Laboratories Ltd, Newhouse, Lanarkshire, ML1 5SH, UK |
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Abstract: | Altered activity of the hypothalamic pituitary adrenal (HPA) axis is one of the most commonly observed neuroendocrine abnormalities
in patients suffering from major depressive disorder (MDD). Altered cortisol secretion can be found in as many as 80% of depressed
patients. This observation has led to intensive clinical and preclinical research aiming to better understand the molecular
mechanisms which underlie the alteration of the HPA axis responsiveness in depressive illness. Dysfunctional glucocorticoid
receptor (GR) mediated negative feedback regulation of cortisol levels and changes in arginine vasopressin (AVP)/vasopressin
V1b receptor and corticotrophin-releasing factor/CRF1 receptor regulation of adrenocotricotrophin (ACTH) release have all been implicated in over-activity of the HPA axis. Agents
that intervene with the mechanisms involved in (dys)regulation of cortisol synthesis and release are under investigation as
possible therapeutic agents. The current status of some of these approaches is described in this review.
Special issue article in honor of George Fink. |
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Keywords: | Depression Stress HPA axis Cortisol AVP CRF |
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