CO2 reactivity as a biomarker of exposure-based therapy non-response: study protocol
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 inf...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-12-01
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| Series: | BMC Psychiatry |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12888-022-04478-x |
| _version_ | 1797973568664895488 |
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| author | Jasper A. J. Smits Marie-H. Monfils Michael W. Otto Michael J. Telch Jason Shumake Justin S. Feinstein Sahib S. Khalsa Adam R. Cobb E. Marie Parsons Laura J. Long Bryan McSpadden David Johnson Alma Greenberg Exposure Therapy Consortium |
| author_facet | Jasper A. J. Smits Marie-H. Monfils Michael W. Otto Michael J. Telch Jason Shumake Justin S. Feinstein Sahib S. Khalsa Adam R. Cobb E. Marie Parsons Laura J. Long Bryan McSpadden David Johnson Alma Greenberg Exposure Therapy Consortium |
| author_sort | Jasper A. J. Smits |
| collection | DOAJ |
| description | 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 (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. Methods We 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. 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). |
| first_indexed | 2024-04-11T04:05:15Z |
| format | Article |
| id | doaj.art-77abed7eb38649418206c250480c8ac3 |
| institution | Directory Open Access Journal |
| issn | 1471-244X |
| language | English |
| last_indexed | 2024-04-11T04:05:15Z |
| publishDate | 2022-12-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Psychiatry |
| spelling | doaj.art-77abed7eb38649418206c250480c8ac32023-01-01T12:24:18ZengBMCBMC Psychiatry1471-244X2022-12-0122111510.1186/s12888-022-04478-xCO2 reactivity as a biomarker of exposure-based therapy non-response: study protocolJasper A. J. Smits0Marie-H. Monfils1Michael W. Otto2Michael J. Telch3Jason Shumake4Justin S. Feinstein5Sahib S. Khalsa6Adam R. Cobb7E. Marie Parsons8Laura J. Long9Bryan McSpadden10David Johnson11Alma Greenberg12Exposure Therapy ConsortiumDepartment of Psychology and Institute for Mental Health Research, University of Texas at AustinDepartment of Psychology and Institute for Mental Health Research, University of Texas at AustinDepartment of Psychological and Brain Sciences, Boston UniversityDepartment of Psychology and Institute for Mental Health Research, University of Texas at AustinDepartment of Psychology and Institute for Mental Health Research, University of Texas at Austin3The Laureate Institute for Brain Research3The Laureate Institute for Brain ResearchDepartment of Psychology and Institute for Mental Health Research, University of Texas at AustinDepartment of Psychological and Brain Sciences, Boston UniversityDepartment of Psychological and Brain Sciences, Boston UniversityDepartment of Psychology and Institute for Mental Health Research, University of Texas at AustinDepartment of Psychology and Institute for Mental Health Research, University of Texas at AustinDepartment of Psychological and Brain Sciences, Boston UniversityAbstract 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 (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. Methods We 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. 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).https://doi.org/10.1186/s12888-022-04478-xPanic disorderSocial anxiety disorderObsessive–compulsive disorderGeneralized anxiety disorderPosttraumatic stress disorderExposure therapy |
| spellingShingle | Jasper A. J. Smits Marie-H. Monfils Michael W. Otto Michael J. Telch Jason Shumake Justin S. Feinstein Sahib S. Khalsa Adam R. Cobb E. Marie Parsons Laura J. Long Bryan McSpadden David Johnson Alma Greenberg Exposure Therapy Consortium CO2 reactivity as a biomarker of exposure-based therapy non-response: study protocol BMC Psychiatry Panic disorder Social anxiety disorder Obsessive–compulsive disorder Generalized anxiety disorder Posttraumatic stress disorder Exposure therapy |
| title | CO2 reactivity as a biomarker of exposure-based therapy non-response: study protocol |
| title_full | CO2 reactivity as a biomarker of exposure-based therapy non-response: study protocol |
| title_fullStr | CO2 reactivity as a biomarker of exposure-based therapy non-response: study protocol |
| title_full_unstemmed | CO2 reactivity as a biomarker of exposure-based therapy non-response: study protocol |
| title_short | CO2 reactivity as a biomarker of exposure-based therapy non-response: study protocol |
| title_sort | co2 reactivity as a biomarker of exposure based therapy non response study protocol |
| topic | Panic disorder Social anxiety disorder Obsessive–compulsive disorder Generalized anxiety disorder Posttraumatic stress disorder Exposure therapy |
| url | https://doi.org/10.1186/s12888-022-04478-x |
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