Increased ACTH concentrations associated with cholecystokinin tetrapeptide-induced panic attacks in patients with...

Preclinical findings on the role of corticotropin releasing hormone (CRH) in stress and anxiety, on the interaction of CRH and cholecystokinin (CCK) in modulating anxiety, as well as the blunted corticotropin (ACTH) response to CRH in panic disorder suggest that CRH may play a role in panic disorder. To further characterize the role of the hypothalamic-pituitary-adrenocortical (HPA) system in panic disorder, we compared patients with and without CCK tetrapeptide (CCK-4) induced panic attacks. Twenty-four patients with panic disorder were given injections of CCK-4 (25 micrograms). Panic attacks, psychopathological changes, as well as ACTH and cortisol secretion were recorded. Fifteen of the 24 patients experienced a panic attack after CCK-4. ACTH secretion was significantly higher in the patients with CCK-4-induced panic attacks than in those without such attacks. The patients without CCK-4-induced attacks had a brief but less pronounced increase in ACTH concentrations. Cortisol concentrations were not significantly increased after CCK-4 administration. The increased ACTH concentrations suggest that the activation of the HPA system in CCK-4-induced panic attacks plays a physiological role. CRH may be involved in experimentally-occurring and perhaps in naturally-occurring panic attacks as well.