CO <sub>2</sub> reactivity as a biomarker of exposure-based therapy non-response: study protocol

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Abstract

Background

Exposure-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 (CO ₂) 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 CO ₂ reactivity as a biomarker of exposure-based therapy non-response.

Methods

We will assess CO ₂ reactivity in 600 adults meeting criteria for one or more fear- or anxiety-related disorders prior to providing open exposure-based therapy. By incorporating CO ₂ 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 CO ₂ 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.

Discussion

Representing 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 registration

ClinicalTrials.gov Identifier: NCT05467683 (20/07/2022).

Related collections

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Author and article information

Contributors

Jasper A. J. Smits: smits@utexas.edu

Journal

Journal ID (nlm-ta): BMC Psychiatry

Journal ID (iso-abbrev): BMC Psychiatry

Title: BMC Psychiatry

Publisher: BioMed Central (London )

ISSN (Electronic): 1471-244X

Publication date (Electronic): 27 December 2022

Publication date PMC-release: 27 December 2022

Publication date Collection: 2022

Volume: 22

Electronic Location Identifier: 831

Affiliations

[1 ]GRID grid.89336.37, ISNI 0000 0004 1936 9924, Department of Psychology and Institute for Mental Health Research, , University of Texas at Austin, ; 1 University Station, Austin, TX 78712 USA

[2 ]GRID grid.189504.1, ISNI 0000 0004 1936 7558, Department of Psychological and Brain Sciences, , Boston University, ; 900 Commonwealth Avenue, Floor 2, Boston, MA 02215 USA

[3 ]GRID grid.417423.7, ISNI 0000 0004 0512 8863, 3The Laureate Institute for Brain Research, ; 6655 South Yale Ave., Tulsa, Oklahoma 74136 USA

[4 ]GRID grid.259828.c, ISNI 0000 0001 2189 3475, Department of Psychiatry and Behavioral Sciences, , Medical University of South Carolina and Ralph H. Johnson VAHCS, ; 67 President Street MSC 862, Charleston, SC 29425 USA

Article

Publisher ID: 4478

DOI: 10.1186/s12888-022-04478-x

PMC ID: 9793569

PubMed ID: 36575425

SO-VID: 82d47bcc-ba6f-4526-a737-ee051ca8b31d

License:

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 21 November 2022

Date accepted : 15 December 2022

Funding

Funded by: FundRef http://dx.doi.org/10.13039/100000025, National Institute of Mental Health;

Award ID: R01MH125951

Award ID: R01MH125949

Award ID: R01MH125951

Award Recipient : Jasper A. J. Smits Marie-H. Monfils Michael W. Otto Michael J. Telch Jason Shumake

Custom metadata

ScienceOpen disciplines: Clinical Psychology & Psychiatry

Keywords: panic disorder,social anxiety disorder,obsessive–compulsive disorder,generalized anxiety disorder,posttraumatic stress disorder,exposure therapy,biomarker,orexin,co2 challenge,clinical trial

Data availability:

ScienceOpen disciplines: Clinical Psychology & Psychiatry

Keywords: panic disorder, social anxiety disorder, obsessive–compulsive disorder, generalized anxiety disorder, posttraumatic stress disorder, exposure therapy, biomarker, orexin, co2 challenge, clinical trial

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