In spite of excessive fear during a panic attack, studies have found no or little evidence for an activation of cortisol during natural panic attacks. Whether this phenomenon is related to psychopathology or outcome of psychotherapy is unknown. In this study, 10 patients with panic disorder and agoraphobia were treated with cognitive behavioural therapy including 3 in-vivo exposures (flooding) to individual phobic situations. Before, during and after exposure, the level of subjective fear was assessed and blood was collected simultaneously. Cortisol and ACTH were analysed from plasma. Ten matched healthy control subjects went through the same procedure. Fear and stress hormones during exposure were compared in patients and controls as well as related to therapy outcome at the end of therapy and 2 follow-ups in patients. Results showed that the concentrations of cortisol and ACTH did not significantly increase during exposure. Patients’ cortisol concentrations were higher than those of controls at baseline and during exposure, while ACTH concentrations were comparable before and during exposure, and even lower than those of controls at recovery. Cortisol concentrations were moderately but consistently correlated to therapy outcome, i.e. patients with least cortisol release during exposure profited least from therapy. The study showed that a lack of stimulation of the HPA system at repeated confrontation with the phobic situation was related to therapeutic outcome. Mechanisms of action via the influence of cortisol on extinction learning or the inhibition of central excitatory neurotransmission are conceivable.
During panic attacks, patients with panic disorder experience excessive fear accompanied by a range of seemingly dangerous body sensations like tachycardia, dyspnoea, trembling, sweating, chest pain, dizziness, paresthesia in the extremities and visual dysfunction. Accordingly, they experience massive stress, often with fear of loosing control or even fear of death. Therefore, one would expect a strong activation of the hypothalamus-pituitary-adrenal (HPA) axis in those patients. Astonishingly, studies that have measured cortisol during natural panic attacks so far found either no (Woods et al., 1987 and Cameron et al., 1987) or little (Bandelow et al., 2000) increase of this stress hormone in patients with panic disorder.
The occurrence of panic attacks in certain situations, their association with the context and its subsequent generalization is commonly assumed to be the basis of panic disorder and agoraphobia due to classical and instrumental fear conditioning (Mowrer, 1939). Similarly, exposure therapy is regarded as the clinical equivalent to extinction training (Bouton et al., 2001 and Mineka and Zinbarg, 1996). As such, the investigation of HPA axis function during situationally induced panic attacks in panic disorder is still of considerable interest with respect to the known role of stress hormones in fear conditioning, retrieval, reconsolidation and fear extinction (for review see McGaugh and Roozendaal, 2009, McGaugh and Roozendaal, 2002 and Myers and Davis, 2007).
So far, consequences of the observed lack of HPA responsiveness in patients with panic disorder and agoraphobia during in-vivo exposures have not been investigated in a prospective manner. Further, ACTH has not been monitored in real-life panic attacks so far, although both stress hormones are often dissociated in their response pattern (Bornstein et al., 2008). For this reason, we closely monitored cortisol and ACTH concentrations during in-vivo exposure therapy in 10 patients with agoraphobia and panic disorder and compared them to matched healthy controls which underwent the same procedure. We further analysed whether fear levels or stress hormone concentrations during exposure can predict therapy outcome in the patients.
