1/2: CO2 Reactivity as a Biomarker of Non-response to Exposure-based Therapy

1/2：二氧化碳反应性作为暴露治疗无反应的生物标志物

• 批准号: 10363873
• 负责人: Marie H. Monfils
• 金额: $ 76.38万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-05-01 至 2027-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10363873
• 关键词: Address; Adult; Algorithms; Animals; Anxiety; Anxiety Disorders; Area; Basic Science; Benchmarking; Biological Assay; Biological Markers; Boston; Carbon Dioxide; Clinic; Clinical; Clinical assessments; DSM-V; Data; Development; Diagnosis; Disease; Disease remission; Elements; Enrollment; Exposure to; Extinction (Psychology); Fright; Future; Genotype; Goals; Human Resources; Hypercapnia; Hyperventilation; Impairment; Intervention; Investigation; Lead; Link; Measures; Mediating; Middle Hypothalamus; Modeling; National Institute of Mental Health; Neurons; Observational Study; Obsessive compulsive behavior; Obsessive-Compulsive Disorder; Panic Disorder; Participant; Patients; Phenotype; Plasma; Post-Traumatic Stress Disorders; Predictive Value; Procedures; Protocols documentation; Proxy; Public Health; ROC Curve; Rattus; Recovery; Research; Resources; Rodent; Role; Saliva; Sample Size; Sampling; Selection for Treatments; Severities; Signal Transduction; Site; Specificity; Speed; Strategic Planning; Structure; Symptoms; System; Testing; Translating; Translations; Trauma; Treatment Cost; Work; anxiety treatment; anxiety-related disorders; austin; base; biomarker performance; biomarker selection; clinical practice; design; effective therapy; follow-up; hypocretin; indexing; meetings; novel marker; personalized medicine; predictive modeling; productivity loss; prognostic; prospective; receptor; respiratory challenge; response; sound; stressor; translation to humans; treatment strategy

PROJECT SUMMARY/ABSTRACT Exposure-based therapy is an effective first-line treatment for anxiety-, obsessive-compulsive and trauma- and stressor-related disorders. 1–6 However, many patients fail to respond or achieve remission with exposure- based therapy, 7–11 resulting in “unnecessary” prolonged suffering, loss of productivity, and poorly used resources. Making available a biomarker assay that can aid clinicians and patients in treatment selection has the potential to have considerable public health impact. Basic research on fear extinction - a core mechanism of action of exposure-based therapy - may inform the development of a biomarker for the selection (yes/no) of exposure-based therapy. Growing evidence links 12,13 14–16 orexin system activity to deficits in fear extinction.17–20 Our group has demonstrated that reactivity to CO2 challenge, which is a safe, affordable and easy-to-implement procedure, can serve as a proxy for orexin system activity and predicts fear extinction deficits in rodents.21 Building upon this basic research, the goal for the propo sed study is to validate CO2 reactivity as a biomarker of exposure-based therapy non-response. To this end, we will assess CO2 reactivity in 600 adults meeting for one or more fear- or anxiety-related disorders prior to providing open, state-of-the art, transdiagnostic exposure-based therapy. By incorporating CO2 reactivity into a multivariate model predicting treatment non-response that also includes reactivity to hyperventilation as well as a number of related and theoretically-relevant prognostic variables, we will establish the mechanistic specificity and the additive predictive value of the putative biomarker. By developing models independently within two study sites and predicting the other site's data, we will validate that the results are likely to generalize to future clinical samples. The proposed study represents a necessary stage in translating basic research to strategies for treatment selection. The investigation addresses an important public health issue by testing an accessible clinical assessment strategy - informed by basic research - that may lead to a more effective treatment selection (personalized medicine) for patients with anxiety- and fear-related disorders and enhance our understanding of the mechanisms governing exposure-based therapy.

项目摘要/摘要 基于暴露的治疗是一种有效的一线治疗，用于焦虑，强迫症和创伤 和与压力源有关的疾病。 1–6然而，许多患者未能通过暴露而做出反应或缓解 - 基于疗法，7-11导致“不必要”的长期苦难，生产力降低，并且使用不良 资源。提供可以帮助临床医生和患者进行治疗选择的生物标志物测定法 具有相当大的公共卫生影响的潜力。 关于恐惧扩展的基础研究 - 基于暴露疗法的核心作用机理 - 可能会告知 开发基于暴露疗法的（是/否）的生物标志物。越来越多的证据联系 12,13 14-16 OREXIN系统的活动要在恐惧扩展中定义。17–20我们的小组证明了对CO2的反应性 挑战是一种安全，负担得起且易于实施的程序，可以作为Orexin的代理 系统活动和预测恐惧扩展在啮齿动物中定义。21 在这项基础研究的基础上，提案的目标 SED研究是为了验证二氧化碳反应性 基于暴露的治疗无反应的生物标志物。 为此，我们将评估 二氧化碳反应性 600名成人 在提供开放的，最先进的之前，会开会或多种恐惧或动画相关的疾病 基于转诊的基于接触的治疗。通过将CO2反应性纳入预测的多元模型 治疗无响应也包括对过度换气以及许多相关和许多相关和 理论上与预后变量有关，我们将建立机械特异性和添加 推定生物标志物的预测价值。通过在两个研究站点中独立开发模型， 预测另一个站点的数据，我们将验证结果可能会推广到未来的临床 样品。 拟议的研究是将基础研究转化为治疗策略的必要阶段 选择。该投资通过测试可访问的临床来解决重要的公共卫生问题 评估策略 - 由基础研究告知 - 可能导致更有效的治疗选择 （个性化医学）针对患有焦虑症和恐惧相关疾病的患者，并增强我们对 基于暴露的治疗的机制。