Panic disorder is a frequent and disabling mental disorder characterized by recurrent periods or abrupt surges of intense fear or
discomfort, the panic attacks. The clinical phenomenology of panic attacks suggests a prominent role of a disturbed stress response regulation
in the aetiopathology of this disorder. We summarize the results of challenge tests of the hypothalamus-pituitary-adrenocortical
(HPA) axis in panic disorder and give an overview of studies using psychosocial challenge paradigms. The results of HPA axis challenge
tests suggest an increased expression of the hypothalamic neuropeptides, but an intact negative feedback inhibition at the level of the pituitary.
Psychosocial challenge tests give evidence for dissociation between the subjective stress response and the HPA axis response in
panic disorder, which might be the result of an over-focussed self-monitoring leading to an enhanced stress perception despite normal
HPA axis activation. We integrated these findings in a cognitive stress control model suggesting that panic disorder patients develop efficient
strategies to control the somatic stress response despite a hypothalamic hyperdrive of the HPA axis. To employ these strategies at
the right time, patients acquired an enhanced perception of stress symptoms, leading to the reported dissociation of the subjective and
HPA axis response. It can be inferred from these findings that cognitive behavioral therapy addressing over-focussed self-monitoring and
maladaptive control strategies in combination with pharmacological treatment against over-expression of the hypothalamic neuropeptides
should be an effective treatment in severe forms of panic disorder, which corresponds with recent treatment guidelines.
Keywords: Panic disorder, HPA axis, dexamethasone suppression test, CRH stimulation test, dex/CRH test, psychosocial challenge, Trier
Social Stress Test
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