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: 7262184
• 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/7262184
• 关键词: 4-nitrosodimethylaniline; Acute; Address; Affect; Agonist; Animal Experimentation; Animal Model; Animals; Anxiety; Anxiety Disorders; Behavioral; Clinic; Cognitive; Cognitive Therapy; Condition; 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; Mental Depression; Morbidity - disease rate; Neurotransmitters; Numbers; 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; Standards of Weights and Measures; Stimulus; Symptoms; Testing; Therapeutic procedure; Translating; Translational Research; Treatment outcome; Week; Work; base; cognitive change; conditioned fear; cost; follow-up; 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相关。尽管在经验文献中，认知行为疗法（CBT）在治疗SAD方面取得了一些最好的结果，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，考虑到SAD的患病率和伴随的发病率，以及治疗后的持续性，迫切需要开发新的干预措施来改善结果。在CBT中，核心治疗程序包括反复和长时间暴露于令人恐惧的社会情境中，使患者在这些刺激的存在下获得安全感，从而使恐惧消失。暴露疗法是基于条件性恐惧消失的动物模型，最近的动物研究已经绘制了一些与恐惧消失有关的核心途径和神经递质。d -环丝氨酸（DCS）是谷氨酸NDMA受体部位的激动剂，在动物和一些人类试验中似乎可以增强学习能力，促进条件性恐惧的消除过程。因此，来自动物恐惧消退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，系统评估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次CBT治疗的相对短期和长期益处，其中包括5次dcs增强（50毫克）治疗和5次安慰剂增强治疗。此外，我们将探讨治疗变化的潜在中介和调节因子。我们将随机抽取192名患者，在每个部位采用相同的方案。我们利用3个治疗点的合作调查小组来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研究的关键阶段，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，该干预措施可能导致更有效和更有效地应用基于经验的社会心理干预措施来治疗SAD。