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糖皮质激素用于治疗创伤后应激障碍和恐惧症:一种新的治疗方法。

Glucocorticoids for the treatment of post-traumatic stress disorder and phobias: a novel therapeutic approach.

作者信息

de Quervain Dominique J-F, Margraf Jürgen

机构信息

Division of Psychiatry Research, University of Zürich, Lenggstr. 31, 8032 Zürich, Switzerland.

出版信息

Eur J Pharmacol. 2008 Apr 7;583(2-3):365-71. doi: 10.1016/j.ejphar.2007.11.068. Epub 2008 Jan 24.

Abstract

Post-traumatic stress disorder (PTSD) and phobias belong to the most common anxiety disorders and to the most common psychiatric illnesses in general. In both disorders, aversive memories are thought to play an important role in the pathogenesis and symptomatology. Previously, we have reported that elevated glucocorticoid levels inhibit memory retrieval in animals and healthy humans. We therefore hypothesized that the administration of glucocorticoids might also inhibit the retrieval of aversive memory, thereby reducing symptoms in patients with PTSD and phobias. In recent clinical studies, we found first evidence to support this hypothesis. In patients with PTSD, low-dose cortisol treatment for one month reduced symptoms of traumatic memories without causing adverse side effects. Furthermore, we found evidence for a prolonged effect of the cortisol treatment. Persistent retrieval and reconsolidation of traumatic memories is a process that keeps these memories vivid and thereby the disorder alive. By inhibiting memory retrieval, cortisol may weaken the traumatic memory trace, and thus reduce symptoms even beyond the treatment period. In patients with social phobia, we found that a single oral administration of cortisone 1 h before a socio-evaluative stressor significantly reduced self-reported fear during the anticipation-, exposure-, and recovery phase of the stressor. In subjects with spider phobia, repeated oral administration of cortisol 1 h before exposure to a spider photograph induced a progressive reduction of stimulus-induced fear. This effect was maintained when subjects were exposed to the stimulus again two days after the last cortisol administration, indicating that cortisol facilitated the extinction of phobic fear. In conclusion, by a common mechanism of reducing the retrieval of aversive memories, glucocorticoids may be suited for the treatment of PTSD as well as phobias. More studies are needed to further evaluate the therapeutic efficacy of glucocorticoids in the treatment of anxiety disorders and to explore the potential of combining glucocorticoid treatment with psychotherapy.

摘要

创伤后应激障碍(PTSD)和恐惧症属于最常见的焦虑症,也是一般意义上最常见的精神疾病。在这两种疾病中,厌恶记忆被认为在发病机制和症状学中起重要作用。此前,我们曾报道糖皮质激素水平升高会抑制动物和健康人类的记忆提取。因此,我们推测给予糖皮质激素也可能抑制厌恶记忆的提取,从而减轻PTSD和恐惧症患者的症状。在最近的临床研究中,我们首次发现了支持这一假设的证据。在PTSD患者中,低剂量皮质醇治疗一个月可减轻创伤记忆的症状,且未引起不良副作用。此外,我们还发现了皮质醇治疗具有长期效应的证据。创伤记忆的持续提取和重新巩固是一个使这些记忆保持鲜活从而使疾病持续存在的过程。通过抑制记忆提取,皮质醇可能会削弱创伤记忆痕迹,从而甚至在治疗期过后仍能减轻症状。在社交恐惧症患者中,我们发现,在社会评价性应激源出现前1小时口服一次可的松,可显著减轻应激源预期期、暴露期和恢复期的自我报告恐惧。在蜘蛛恐惧症患者中,在接触蜘蛛照片前1小时重复口服皮质醇会使刺激诱发的恐惧逐渐减轻。在最后一次给予皮质醇两天后再次让受试者接触该刺激时,这种效果仍然存在,这表明皮质醇促进了恐惧的消退。总之,通过减少厌恶记忆提取的共同机制,糖皮质激素可能适用于治疗PTSD和恐惧症。需要更多研究来进一步评估糖皮质激素在治疗焦虑症方面的疗效,并探索将糖皮质激素治疗与心理治疗相结合的潜力。

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