CO2 reactivity as a biomarker of exposure-based therapy non-response: study protocol

BMC Psychiatry

Study Protocol

Sahib S. Khalsa¹  Justin S. Feinstein¹  Laura J. Long²  Michael W. Otto²  E. Marie Parsons²  Alma Greenberg²  Jasper A. J. Smits³  Marie-H. Monfils³  David Johnson³  Michael J. Telch³  Bryan McSpadden³  Jason Shumake³  Adam R. Cobb⁴ 

[1] 3The Laureate Institute for Brain Research, 6655 South Yale Ave., 74136, Tulsa, Oklahoma, USA;Department of Psychological and Brain Sciences, Boston University, 900 Commonwealth Avenue, Floor 2, 02215, Boston, MA, USA;Department of Psychology and Institute for Mental Health Research, University of Texas at Austin, 1 University Station, 78712, Austin, TX, USA;Department of Psychology and Institute for Mental Health Research, University of Texas at Austin, 1 University Station, 78712, Austin, TX, USA;Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina and Ralph H. Johnson VAHCS, 67 President Street MSC 862, 29425, Charleston, SC, USA;

关键词: Panic disorder;    Social anxiety disorder;    Obsessive–compulsive disorder;    Generalized anxiety disorder;    Posttraumatic stress disorder;    Exposure therapy;    Biomarker;    Orexin;    CO challenge;    Clinical trial;   

DOI  :  10.1186/s12888-022-04478-x

 received in 2022-11-21, accepted in 2022-12-15,  发布年份 2022

来源: Springer

【 摘 要 】

BackgroundExposure-based therapy is an effective first-line treatment for anxiety-, obsessive–compulsive, and trauma- and stressor-related disorders; however, many patients do not improve, resulting in prolonged suffering and poorly used resources. Basic research on fear extinction may inform the development of a biomarker for the selection of exposure-based therapy. Growing evidence links orexin system activity to deficits in fear extinction and we have demonstrated that reactivity to an inhaled carbon dioxide (CO2) challenge—a safe, affordable, and easy-to-implement procedure—can serve as a proxy for orexin system activity and predicts fear extinction deficits in rodents. Building upon this basic research, the goal for the proposed study is to validate CO2 reactivity as a biomarker of exposure-based therapy non-response.MethodsWe will assess CO2 reactivity in 600 adults meeting criteria for one or more fear- or anxiety-related disorders prior to providing open 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 predictor variables, we will establish the mechanistic specificity and the additive predictive utility of the potential CO2 reactivity biomarker. By developing models independently within two study sites (University of Texas at Austin and Boston University) and predicting the other site’s data, we will validate that the results are likely to generalize to future clinical samples.DiscussionRepresenting a necessary stage in translating basic research, this investigation addresses an important public health issue by testing an accessible clinical assessment strategy that may lead to a more effective treatment selection (personalized medicine) for patients with anxiety- and fear-related disorders, and enhanced understanding of the mechanisms governing exposure-based therapy.Trial registrationClinicalTrials.gov Identifier: NCT05467683 (20/07/2022).

【 授权许可】

CC BY   
© The Author(s) 2022

【 图 表 】

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