2/3-Exposure D-Cycloserine Enhancement and Genetic Modulators in Panic Disorder

恐慌症中的 2/3 暴露 D-环丝氨酸增强剂和遗传调节剂

• 批准号: 7616453
• 负责人: DAVID F TOLIN
• 金额: $ 20.97万
• 依托单位: HARTFORD HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-24 至 2013-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7616453
• 关键词: Acute; Address; Adult; Adverse event; Aftercare; Agonist; Agoraphobia; Amygdaloid structure; Anxiety Disorders; Basic Science; Brain-Derived Neurotrophic Factor; Combined Modality Therapy; Cycloserine; Dose; Double-Blind Method; Employee Strikes; Extinction (Psychology); Fostering; Fright; Genes; Genetic; Genetic Enhancement; Glutamates; Height; Impairment; Individual; Intervention; Laboratory Animals; Lead; Long-Term Effects; Mediating; N-Methyl-D-Aspartate Receptors; NTRK2 gene; Neurobiology; Outpatients; Panic Disorder; Patients; Pilot Projects; Placebos; Public Health; Randomized Controlled Trials; Relative (related person); Research; Safety; Severities; Site; Symptoms; System; Translational Research; Treatment Efficacy; Treatment outcome; Validation; alternative treatment; base; cognitive behavior therapy; conditioned fear; exposed human population; follow up assessment; follow-up; learning extinction; neural circuit; novel strategies; pill; programs; psychosocial; response; social; success; treatment program; treatment response; treatment site

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. This study capitalizes on the recent successes in translational research to investigate the benefits of the addition of d-cycloserine to a program of brief exposure-based CBT for the treatment of panic disorder with or without agoraphobia. This study addresses an important public health issue by assessing an intervention that may help lead to a more efficient and effective application of empirically-based psychosocial interventions for the treatment of panic disorder and other anxiety disorders. This novel strategy of combining exposure-based treatment and d-cycloserine remains a particularly promising strategy among disappointing alternatives for the treatment of individuals with anxiety disorders, and our research will also provide valuable information on potential genetic moderators of both CBT efficacy as well as d-cycloserine enhancement of this efficacy.

描述（由申请人提供）：这是一个3中心（PIS：Otto，Pollack，Tolin，Tolin）协作R01。在此应用程序中，我们建议进一步验证和扩展转化研究的明显成功之一。具体而言，关于恐惧灭绝的神经回路的基础研究导致对杏仁核NMDA受体的部分激动剂D-Cycloserine进行了检查，作为能够增强灭绝学习的药物（Davis等，2006a; Davis等，2006b）。在动物实验室成功验证了该策略后，Ressler等人。 （2004年）表明，单剂量的D-胞丝苷（DC）可以增强身高恐惧症成年人的人类暴露范式中的灭绝。我们的研究团队复制了这一激动人心的初步发现，以治疗门诊患者的社交焦虑症（Hofmann等，2006），我们还完成了一项试点研究，表明对其他焦虑症的治疗相似。正如Anderson和Insel（2006）所讨论的那样，这些发现具有促进焦虑症治疗的重大进展的潜力。本研究代表了DC在增加基于暴露的认知行为疗法（CBT）的影响的进一步应用，该疗法现已应用于患有或没有恐惧症的恐慌症的治疗。在此应用中，我们提出了一项在三个治疗部位进行的双盲随机对照试验，以比较与恐慌症患者相比，与安慰剂相比，将基于暴露的CBT与DC相比的相对好处。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指标，尤其是对于DC增强的影响，我们试图确定哪些患者可能对这种形式的短暂，合并治疗特别有反应。这项研究利用了转化研究的最新成功，以调查在基于简短暴露的CBT方案中添加D-胞与甲烯的好处，以治疗有或没有大多表恐惧症的恐慌症。这项研究通过评估一项干预措施来解决一个重要的公共卫生问题，该干预措施可能有助于导致基于经验的社会心理干预措施对恐慌症和其他焦虑症的治疗进行更有效的应用。这种新的基于暴露治疗和D-胞丝烯的新策略仍然是令人失望的焦虑症患者的令人失望的替代方案中的特别有希望的策略，我们的研究还将提供有关CBT功效的潜在遗传主持人以及这种功效增强的D-胞与糖赛的潜在遗传主持人的宝贵信息。