3/3-Exposure D-Cycloserine Enhancement and Genetic Modulators in Panic Disorder

描述（由申请人提供）：这是一个3中心（pi：博士）。奥托，波拉克，托林)合作R01。在这个应用程序中，我们建议进一步验证和扩展翻译研究的一个明显的显著成功。具体来说，对恐惧消退背后的神经回路的基础研究导致了对d-环丝氨酸的研究，d-环丝氨酸是杏仁核中NMDA受体的部分激动剂，能够增强消退学习（Davis et al., 2006a; Davis et al., 2006b）。在动物实验室成功验证了这一策略后，Ressler等人（2004）表明，单剂量的d-环丝氨酸（DCS）可以增强人类暴露范例中恐高成人的灭绝。这一令人兴奋的初步发现被我们的研究团队复制用于治疗门诊患者的社交焦虑症（Hofmann et al., 2006），我们还完成了一项试点研究，表明治疗其他焦虑症的类似益处。正如Anderson和Insel（2006）所讨论的那样，这些发现有可能促进焦虑症治疗方面的重大进展。本研究代表了DCS在增强基于暴露的认知行为疗法（CBT）效果方面的进一步应用，CBT目前已应用于治疗伴有或不伴有广场恐怖症的惊恐障碍。在本申请中，我们提出了一项双盲随机对照试验，在三个治疗地点进行，以比较增加暴露为基础的CBT与DCS相比安慰剂对恐慌症患者的相对益处。此外，通过研究特定基因位点的变异性作为治疗反应的预测因子，特别是对于DCS增强的影响，我们试图确定哪些患者可能对这种简短的联合治疗特别敏感。

DESCRIPTION (provided by applicant): This is a 3-center (PIs: Drs. Otto, Pollack, Tolin) collaborative R01. In this application, we propose to further validate and expand upon one of the apparent striking successes of translational research. Specifically, basic research on the neural circuitry underlying fear extinction led to the examination of d-cycloserine, a partial agonist at the NMDA receptor in the amygdala, as an agent capable of enhancing extinction learning (Davis et al., 2006a; Davis et al., 2006b). Following successful validation of this strategy in the animal laboratory, Ressler et al. (2004) showed that single doses of d-cycloserine (DCS) could enhance extinction in a human exposure paradigm for height phobic adults. This exciting initial finding was replicated by our research team for the treatment of social anxiety disorder in outpatients (Hofmann et al., 2006), and we also have completed a pilot study indicating similar benefits for the treatment of other anxiety disorders. As discussed by Anderson and Insel (2006), these findings have the potential to foster significant advances in the treatment of anxiety disorders. The present study represents the further application of DCS for augmenting the effects of exposure- based cognitive-behavior therapy (CBT), now applied to the treatment of panic disorder with or without agoraphobia. In this application we propose a double-blind randomized controlled trial, conducted at three treatment sites, to compare the relative benefit of augmenting exposure-based CBT with DCS as compared to placebo for patients with panic disorder. In addition, by studying variability at specific gene sites as a predictor of treatment response, particularly for the effects of DCS augmentation, we seek to identify which patients may be particularly responsive to this form of brief, combined treatment.