The role of corticotropin-releasing factor in the pathophysiology of affective and anxiety disorders: laboratory and clinical studies.

M. J. Owens, Charles Nemeroff

Research output: Contribution to journalArticle

161 Citations (Scopus)

Abstract

The unique distribution of corticotropin-releasing factor (CRF) and its receptors within the central nervous system, its pre-eminent role in mediating the endocrine, behavioural, autonomic and immunological effects of stress and its potent effects after direct administration into the CNS all support the hypothesis that alterations in CRF neuronal systems contribute to the pathophysiology of depression and certain anxiety disorders. This report summarizes a series of preclinical and clinical investigations which have sought to test the hypothesis that CRF-containing neurons show alterations in depression and anxiety, and that drugs used to treat these disorders alter CRF neuronal circuits. Direct injection of CRF into the locus ceruleus or nearby parabrachial nucleus evokes an anxiogenic response. Stress increases CRF concentrations in the locus ceruleus, whereas alprazolam, a benzodiazepine anxiolytic, decreases the concentration of the peptide in the same area. Clinical studies reveal that drug-free depressed patients show: (1) hyperactivity of the hypothalamo-pituitary-adrenal axis; (2) increased CRF concentrations in the cerebrospinal fluid; (3) a blunted release of ACTH in response to CRF; (4) a reduced density of CRF receptors in the frontal cortex; (5) pituitary and adrenal gland hypertrophy. These findings are all concordant with hypersecretion of CRF from hypothalamic and extrahypothalamic CRF neurons in depression.

Original languageEnglish
Pages (from-to)296-308; discussion 308
JournalCiba Foundation symposium
Volume172
StatePublished - Jan 1 1993
Externally publishedYes

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Corticotropin-Releasing Hormone
Anxiety Disorders
Mood Disorders
Corticotropin-Releasing Hormone Receptors
Locus Coeruleus
Depression
Autonomic Agents
Alprazolam
Clinical Studies
Neurons
Anti-Anxiety Agents
Frontal Lobe
Pituitary Gland
Adrenal Glands
Benzodiazepines
Pharmaceutical Preparations
Adrenocorticotropic Hormone
Hypertrophy
Cerebrospinal Fluid
Anxiety

ASJC Scopus subject areas

  • Medicine(all)

Cite this

The role of corticotropin-releasing factor in the pathophysiology of affective and anxiety disorders : laboratory and clinical studies. / Owens, M. J.; Nemeroff, Charles.

In: Ciba Foundation symposium, Vol. 172, 01.01.1993, p. 296-308; discussion 308.

Research output: Contribution to journalArticle

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