D-Cycloserine Enhancement of Exposure in Social Phobia

D-环丝氨酸增强社交恐惧症的暴露程度

• 批准号: 7664450
• 负责人: Stefan G. Hofmann
• 金额: $ 32.91万
• 依托单位: BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-19 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7664450
• 关键词: Acute; Address; Affect; Aftercare; Agonist; Animal Experimentation; Animal Model; Animals; Anxiety; Anxiety Disorders; Behavioral; Clinic; Cognitive; Cycloserine; Development; Disease remission; Distress; Ensure; Expectancy; Extinction (Psychology); Fright; Functional disorder; Glutamates; Human; Individual; Intervention; Lead; Learning; Literature; Long-Term Effects; Maps; Mediating; Mediation; Mediator of activation protein; Morbidity - disease rate; Neurotransmitters; Outcome; Pathway interactions; Patients; Pilot Projects; Placebos; Population Heterogeneity; Prevalence; Probability; Process; Protocols documentation; Public Health; Randomized; Randomized Controlled Trials; Relative (related person); Research; Research Personnel; Safety; Severities; Site; Social Phobia; Staging; Stimulus; Symptoms; Testing; Therapeutic procedure; Translating; Translational Research; Treatment outcome; Work; base; cognitive behavior therapy; cognitive change; conditioned fear; cost; depression; follow up assessment; improved; novel; novel strategies; programs; psychosocial; receptor; social; success; treatment site

DESCRIPTION (provided by applicant): Social anxiety disorder (SAD) is among the most common psychiatric conditions and is associated with significant distress and dysfunction in affected individuals. Although treatment with cognitive-behavior therapy (CBT) results in some of the best outcomes in the empirical literature for SAD, many patients do not respond to this intervention and most do not achieve remission. Thus, given the prevalence and attendant morbidity of SAD, and its persistence despite treatment, there is a critical need for the development of novel interventions to improve outcome. In CBT, core therapeutic procedures include repeated and prolonged exposure practices to feared social situations, allowing fears to extinguish as patients acquire a sense of safety in the presence of these stimuli. Exposure therapy is based on animal models of extinction of conditioned fears, and recent animal research has mapped some of the core pathways and neurotransmitters involved in fear extinction. D-cycloserine (DCS), an agonist at the glutamatergic NDMA receptor site appears to augment learning in animals and in some human trials facilitating the process of extinction of conditioned fear. Thus, converging evidence from animal models of fear extinction, and from initial studies in humans, including work from our pilot study, indicates that DCS can facilitate CBT of SAD. We are proposing a 4-year study to systematically assess the efficacy of DCS augmentation of CBT for the treatment of SAD. The study comprises a randomized, controlled trial to compare the relative short-term and long-term benefits of 12 CBT sessions that include 5 DCS-augmented (50 mg) sessions with the same CBT protocol that includes 5 placebo-augmented sessions. In addition, we will explore potential mediators and moderators of treatment change. We will randomize a total of 192 patients with the identical protocol followed at each of the sites. We make use of a collaborating team of investigators across 3 treatment sites to help ensure the timely recruitment of adequate numbers of patients, including an ethnically diverse population. This study represents a crucial stage in translating bench research to the clinic, and testing a novel approach for combining pharmacologic and cognitive-behavioral strategies for treating patients. This study addresses an important public health issue by assessing an intervention that may lead to a more efficient and effective application of empirically based psychosocial interventions for the treatment of SAD.

描述（由申请人提供）：社交焦虑障碍（SAD）是最常见的精神疾病之一，与受影响个体的显著痛苦和功能障碍有关。虽然认知行为疗法（CBT）的治疗结果在SAD的经验文献中是最好的，但许多患者对这种干预没有反应，大多数患者没有达到缓解。因此，鉴于SAD的患病率和伴随的发病率，以及尽管治疗但其持续存在，迫切需要开发新的干预措施以改善结果。在CBT中，核心治疗程序包括重复和长时间暴露于令人恐惧的社会情境，当患者在这些刺激存在时获得安全感时，恐惧就会消失。暴露疗法是基于消除条件性恐惧的动物模型，最近的动物研究已经绘制了一些参与恐惧消除的核心通路和神经递质。D-环丝氨酸（DCS），一种在多巴胺能NDMA受体位点的激动剂，似乎可以增强动物的学习能力，在一些人体试验中，促进条件性恐惧的消退过程。因此，来自恐惧消退动物模型和人类初步研究的证据，包括我们的试点研究，表明DCS可以促进SAD的CBT。我们建议进行一项为期4年的研究，以系统地评估DCS增强CBT治疗SAD的疗效。该研究包括一项随机对照试验，以比较12个CBT会话的相对短期和长期益处，其中包括5个DCS增强（50 mg）会话与相同的CBT协议，其中包括5个安慰剂增强会话。此外，我们将探讨治疗变化的潜在介质和调节剂。我们将在每家临床试验机构按照相同的方案随机分配共计192例患者。我们利用3个治疗中心的研究者合作团队，帮助确保及时招募足够数量的患者，包括不同种族的人群。这项研究代表了将实验室研究转化为临床的关键阶段，并测试了一种结合药理学和认知行为策略治疗患者的新方法。本研究通过评估一种干预措施来解决一个重要的公共卫生问题，这种干预措施可能会导致更有效和更有效地应用基于经验的心理社会干预措施来治疗SAD。