Max Planck Institute of Psychiatry, Kraepelinstr. 2-10, 80804 Munich, Germany.
Curr Pharm Des. 2012;18(35):5675-84. doi: 10.2174/138161212803530880.
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.
惊恐障碍是一种常见且使人丧失能力的精神障碍,其特征是反复出现或突然出现强烈的恐惧或不适,即惊恐发作。惊恐发作的临床现象学表明,应激反应调节紊乱在这种障碍的发病机制中起着重要作用。我们总结了惊恐障碍下丘脑-垂体-肾上腺皮质(HPA)轴挑战试验的结果,并概述了使用心理社会挑战范式的研究。HPA 轴挑战试验的结果表明,下丘脑神经肽的表达增加,但垂体水平的负反馈抑制完整。心理社会挑战试验表明,惊恐障碍患者的主观应激反应与 HPA 轴反应之间存在分离,这可能是由于过度关注自我监测导致尽管 HPA 轴激活正常,但应激感知增强的结果。我们将这些发现整合到一个认知应激控制模型中,该模型表明,尽管 HPA 轴的下丘脑驱动过度,但惊恐障碍患者会发展出有效的策略来控制躯体应激反应。为了在适当的时候使用这些策略,患者对应激症状的感知增强,导致报告中的主观和 HPA 轴反应分离。从这些发现可以推断,针对过度关注自我监测和适应不良控制策略的认知行为疗法结合针对下丘脑神经肽过度表达的药物治疗,应该是严重惊恐障碍的有效治疗方法,这与最近的治疗指南一致。