The Corticosteroid Receptor
Hypothesis of Depression
by
Holsboer F
Max Planck Institute of Psychiatry,
Munich, Germany
Neuropsychopharmacology 2000 Nov 1; 23(5):477-501

ABSTRACT

Signs and symptoms that are characteristic for depression include changes in the setpoint of the hypothalamic-pituitary-adrenocortical (HPA) system, which in the majority of these patients result in altered regulation of corticotropin (ACTH) and cortisol secretory activity. More refined analysis of the HPA system revealed that corticosteroid receptor (CR) signaling is impaired in major depression, resulting among other changes, in increased production and secretion of corticotropin-releasing hormone (CRH, also frequently abbreviated CRF) in various brain regions postulated to be involved in the causality of depression. This article summarizes the clinical and preclinical data, supporting the concept that impaired CR signaling is a key mechanism in the pathogenesis of depression. Mouse genetics, allowing for selective inactivation of genes relevant for HPA regulation and molecular pharmacology, dissecting the intracellular cascade of CR signaling, are the most promising future research fields, suited for identifying genes predisposing to depression. Focusing on these two research lines may also allow to gain insight into understanding how current antidepressants work and further, how more specific targets for future antidepressant drugs can be identified.

CRF
LHPA
Stress
Metyrapone
Ketoconazole
Cortisol blues
Stressed tree shrews
Learned helpless rats
Glucocorticoids and mood
Hippocampal remodelling
Stress, depression and the rat
Corticosteroids and depression
Hormones, the brain and stress
Glucocorticoids and antidepressants
Are antidepressants neuroprotective?
Antiglucocorticoids as antidepressants
A neurotrophic model for stress-related mood disorders
Stress, dynorphin, dysphoria and the kappa opioid system
Regulation of 5-HT1a, glucocorticoid, and mineralocorticoid receptors

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