Hagit Cohen

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.