Salivary cortisol in panic: are males more vulnerable?

OBJECTIVES: The underlying mechanisms of panic attacks (PA's) are still unclear. Theories focusing on these mechanisms differ in their description of the relationship between panic and fear. The main controversy concerns whether a PA resembles the classical flight response, or whether it is qualitatively different from fear. According to the first theory, a PA would result in hypothalamic-pituitary-adrenal axis (HPA-axis) activation, whereas according to the second, it would not. So far, inconclusive results have been reported in studies measuring HPA-axis activity after laboratory evoked PA's. The present study was designed to assess cortisol levels following a 35% CO2 challenge in Panic Disorder (PD) patients compared to healthy volunteers as a measurement of HPA-axis activity. DESIGN: Twenty-three PD patients and 20 healthy volunteers participated in the study. Cortisol was determined in saliva at regular intervals before and after the challenge. Furthermore, attention was paid to possible gender effects. RESULTS: Although the 35% CO2 inhalation induced a significant increase in anxiety, no cortisol increase was found. Moreover, there was no difference between patient and control cortisol values following the 35% CO2 challenge, whereas the delta anxiety scores were far more pronounced in the patient group. Interestingly, male PD patients showed higher cortisol values. CONCLUSIONS: This study may be in accordance with the view that PA's are not accompanied by an important HPA-axis activation. There are some indications for aberrant cortisol secretion in male PD patients. Further research needs to confirm whether male and female PD patients differ in their underlying mechanisms related to HPA-axis activity.

Hypothalamic-pituitary-adrenal axis function following a 35% CO2 inhalation in healthy volunteers.

RATIONALE: The hypothalamic-pituitary-adrenal axis (HPA axis) is a central component of the brain's neuroendocrine response to stress. The extent of increase in cortisol secretion, provides an index of the HPA axis activity, and in this way, objectively reflects perceived stress. In healthy subjects, the 35% CO(2) inhalation does hardly induce stress, as expressed in anxiety. However, inconsistent results have been found in studies investigating the cortisol response following CO(2) inhalation. Clarity has to be reached about the normal reaction to this challenge, especially because this model is still a very valuable method to study central aspects of panic. OBJECTIVES: The present study aimed to test the hypothesis that a single breath of 35% CO(2) would not induce cortisol release in healthy volunteers. METHODS: In the current study, 20 healthy subjects underwent both a 35% CO(2) and a placebo inhalation in a randomised, single blind fashion. Cortisol levels were determined in saliva samples, taken at regular intervals. RESULTS: No differences were found between the CO(2) and the placebo condition. In both conditions a significant time effect was found, which can be subscribed to normal variation in the circadian rhythm. Furthermore, only modest subjective anxiety scores were found in the CO(2) condition. CONCLUSIONS: These results provide biological evidence for the hypothesis that healthy subjects are not affected by the 35% CO(2) challenge in a clinically significant way. Characteristic, PD patients react much stronger to the inhalation. Thus, in addition to psychological parameters, healthy subjects also constitute an ideal comparison group with regard to endocrinological parameters.