A striking pattern of cortisol non-responsiveness to psychosocial stress in patients with panic disorder with concurrent normal cortisol awakening responses

Background: Subtle and inconsistent differences in hypothalamic-pituitary-adrenal (HPA) axis activity have been reported for patients with panic disorder. While these patients show little or no alterations in basal ACTH and cortisol levels, it has been hypothesized that HPA hyperresponsivity was a trait in panic patients when exposed to novel and uncontrollable stimulation. Methods: Thirty-four patients (23 females, mean age 35 yrs) diagnosed with panic disorder were compared to 34 healthy controls matched for age, gender, smoking status, and use of oral contraceptives. Both groups were exposed twice to a potent laboratory stress protocol, the Trier Social Stress Test (TSST) on consecutive days. Free salivary cortisol levels and heart rate responses were repeatedly measured before and following the TSST. In addition, the cortisol awakening response (CAR) was assessed to further investigate HPA reactivity in PD patients. Results: While the TSST induced similar heart rate stress responses in both groups, cortisol responses were clearly absent in the panic patients with normal responses in the controls (F(1.96, 66) = 20.16; p < 0.001). No differences in basal cortisol levels were observed in the extended baseline period. The same cortisol stress non-response patterns were observed when patients with/without comorbid depression, or with/without psychotropic medication were compared. In contrast to their non-response to the psychosocial stressor, panic patients showed a significant CAR. Conclusion: These findings provide strong evidence to suggest that PD patients present with a striking lack of cortisol responsivity to acute uncontrollable psychosocial stress under laboratory conditions. This unresponsiveness of the HPA axis appears to be rather specific, since a normal CAR in the morning could be documented in these patients. Thus, the present results do not support the hypothesis that PD patients show a trait HPA hyperresponsiveness to novel and uncontrollable stimulation. In contrast, the data provide support for a hyporesponsive HPA axis under emotional stress in PD patients. (c) 2009 Elsevier Ltd. All rights reserved.