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

基本信息

批准号：
10614375
负责人：
Marie H. Monfils
金额：
$ 72.3万
依托单位：
UNIVERSITY OF TEXAS AT AUSTIN
依托单位国家：
美国
项目类别：
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/10614375
关键词：
Address Adult Aftercare Algorithms Animals Anxiety Anxiety Disorders Area Basic Science Benchmarking Biological Assay Biological Markers Boston Carbon Dioxide Classification Clinic Clinical Clinical assessments DSM-V Data Development Diagnosis Diagnostic Disease Disease remission Elements Enrollment Exposure to Extinction Fright Future Genotype Goals Human Resources Hypercapnia Hyperventilation Impairment Intervention Investigation Link Measures Mediating Middle Hypothalamus Modeling National Institute of Mental Health Neurons Obsessive compulsive behavior Obsessive-Compulsive Disorder Panic Disorder Participant Patients Phenotype Plasma Post-Traumatic Stress Disorders Prediction of Response to Therapy 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 biomarker identification biomarker performance biomarker selection clinical practice design effective therapy follow-up hypocretin improved indexing meetings novel marker personalized medicine predictive modeling productivity loss prognostic prospective receptor respiratory challenge response sound stressor translation to humans treatment strategy

项目摘要

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.

项目概要/摘要基于暴露的疗法是治疗焦虑症、强迫症和创伤症的有效一线疗法。 1-6 然而，许多患者未能对暴露做出反应或达到缓解。基于治疗，7-11 导致“不必要的”长期痛苦、生产力损失和使用不当提供可以帮助骑士和患者选择治疗方法的生物标志物测定。可能对公共卫生产生重大影响。关于恐惧消退的基础研究——暴露疗法的核心作用机制——可能会提供信息用于选择（是/否）基于暴露的治疗的生物标志物的开发越来越多的证据联系。 12,13 14–16 食欲素系统活动对恐惧消退的缺陷。17-20 我们的小组已经证明，对二氧化碳的反应性 Challenge是一种安全、负担得起且易于实施的程序，可以作为食欲素的替代品系统活动并预测啮齿类动物的恐惧消退缺陷21 在此基础研究的基础上，该提案的目标 sed 研究旨在验证 CO2 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 CO2 反应性 600 名成人在提供开放的、最先进的、通过将 CO2 反应性纳入预测的多变量模型中，进行基于暴露的跨诊断治疗。治疗无反应，还包括对过度换气的反应以及许多相关和理论上相关的预后变量，我们将建立机械特异性和加性通过在两个研究中心独立开发模型来确定假定的生物标志物的预测价值。预测其他站点的数据，我们将验证结果是否可能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该调查通过测试可访问的临床选择来解决一个重要的公共卫生问题。评估策略——以基础研究为基础——可能会导致更有效的治疗选择（个性化医疗）为患有焦虑和恐惧相关疾病的患者提供帮助，并增强我们对基于暴露的治疗的控制机制。