Effects of the cortisol synthesis inhibitor metyrapone on the response to carbon dioxide challenge in panic disorder

Andrey Belgorodsky, Leonid Knyazhansky, Uri Loewenthal, Jonathan Arbelle, Hagit Cohen, Jonathan Benjamin

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Despite the well-known association between the hypothalamic-pituitary- adrenal (HPA) axis and normal fear, it is still unclear (a) to what extent corticotropin releasing hormone (CRH) or cortisol itself mediates fear responses, and (b) to what extent the HPA axis also affects panic disorder. The carbon-dioxide (CO2) challenge has been proposed as a model for panic. Participants received the cortisol synthesis inhibitor metyrapone 30 mg/kg of body weight once and placebo once, with 1 week between challenges, at 2300 h. The following morning, blood was taken far cortisol and ACTH levels, and then participants inhaled a single vital capacity inhalation of 35% CO 2 and 65% oxygen. Before and after the inhalation, participants completed an inventory of the 13 DSM-IV symptoms of panic and the NIMH questionnaire of psychological and physical symptoms. Eight healthy controls and 14 patients with panic disorder completed the protocol. As expected, CO 2 increased measures of anxiety, and metyrapone lowered cortisol and increased ACTH levels. Prechallenge anxiety was modestly lowered by metyrapone, but response to CO2 was not affected. Cortisol and ACTH levels before challenge partly predicted the response to CO2. The results support an anxiogenic role for cortisol in stress, and suggest that the pathophysiological mechanism that mediates CO2-induced panic differs from those underlying other kinds of anxiety.

Original languageEnglish
Pages (from-to)143-148
Number of pages6
JournalDepression and Anxiety
Volume21
Issue number3
DOIs
StatePublished - 4 Aug 2005

Keywords

  • Anxiety
  • Neuroendocrinology
  • Pharmacology

ASJC Scopus subject areas

  • Clinical Psychology
  • Psychiatry and Mental health

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