Plasma TNFSF10 levels associated with acamprosate treatment response in patients with alcohol use disorder
Acamprosate is an anti-craving drug used in alcohol use disorder (AUD) pharmacotherapy. However, only a subset of patients achieves optimal treatment outcomes. The identification of predictive biomarkers of acamprosate treatment response in patients with AUD would be a substantial advance in addicti...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-09-01
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| Series: | Frontiers in Pharmacology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.986238/full |
| _version_ | 1828366757030526976 |
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| author | Ming-Fen Ho Cheng Zhang Irene Moon Brandon J. Coombes Joanna Biernacka Michelle Skime Doo-Sup Choi Paul E. Croarkin Mark A. Frye Quyen Ngo Cedric Skillon Tyler S. Oesterle Victor M. Karpyak Hu Li Richard M. Weinshilboum |
| author_facet | Ming-Fen Ho Cheng Zhang Irene Moon Brandon J. Coombes Joanna Biernacka Michelle Skime Doo-Sup Choi Paul E. Croarkin Mark A. Frye Quyen Ngo Cedric Skillon Tyler S. Oesterle Victor M. Karpyak Hu Li Richard M. Weinshilboum |
| author_sort | Ming-Fen Ho |
| collection | DOAJ |
| description | Acamprosate is an anti-craving drug used in alcohol use disorder (AUD) pharmacotherapy. However, only a subset of patients achieves optimal treatment outcomes. The identification of predictive biomarkers of acamprosate treatment response in patients with AUD would be a substantial advance in addiction medicine. We designed this study to use proteomics data as a quantitative biological trait as a step toward identifying inflammatory modulators that might be associated with acamprosate treatment outcomes. The NIAAA-funded Mayo Clinic Center for the Individualized Treatment of Alcoholism study had previously recruited 442 AUD patients who received 3 months of acamprosate treatment. However, only 267 subjects returned for the 3-month follow-up visit and, as a result, had treatment outcome information available. Baseline alcohol craving intensity was the most significant predictor of acamprosate treatment outcomes. We performed plasma proteomics using the Olink target 96 inflammation panel and identified that baseline plasma TNF superfamily member 10 (TNFSF10) concentration was associated with alcohol craving intensity and variation in acamprosate treatment outcomes among AUD patients. We also performed RNA sequencing using baseline peripheral blood mononuclear cells from AUD patients with known acamprosate treatment outcomes which revealed that inflammation-related pathways were highly associated with relapse to alcohol use during the 3 months of acamprosate treatment. These observations represent an important step toward advancing our understanding of the pathophysiology of AUD and molecular mechanisms associated with acamprosate treatment response. In conclusion, applying omics-based approaches may be a practical approach for identifying biologic markers that could potentially predict alcohol craving intensity and acamprosate treatment response. |
| first_indexed | 2024-04-14T05:49:22Z |
| format | Article |
| id | doaj.art-445a37043746454796c7800fa3f24d90 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-14T05:49:22Z |
| publishDate | 2022-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-445a37043746454796c7800fa3f24d902022-12-22T02:09:10ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-09-011310.3389/fphar.2022.986238986238Plasma TNFSF10 levels associated with acamprosate treatment response in patients with alcohol use disorderMing-Fen Ho0Cheng Zhang1Irene Moon2Brandon J. Coombes3Joanna Biernacka4Michelle Skime5Doo-Sup Choi6Paul E. Croarkin7Mark A. Frye8Quyen Ngo9Cedric Skillon10Tyler S. Oesterle11Victor M. Karpyak12Hu Li13Richard M. Weinshilboum14Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, United StatesDepartment of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, United StatesDepartment of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, United StatesDivision of Computational Biology, Quantitative Health Sciences, Rochester, MN, United StatesDivision of Computational Biology, Quantitative Health Sciences, Rochester, MN, United StatesDepartment of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, United StatesDepartment of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, United StatesDepartment of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, United StatesDepartment of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, United StatesHazelden Betty Ford Foundation, Mayo Clinic, Center City, MN, United StatesHazelden Betty Ford Foundation, Mayo Clinic, Center City, MN, United StatesDepartment of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, United StatesDepartment of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, United StatesDepartment of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, United StatesDepartment of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, United StatesAcamprosate is an anti-craving drug used in alcohol use disorder (AUD) pharmacotherapy. However, only a subset of patients achieves optimal treatment outcomes. The identification of predictive biomarkers of acamprosate treatment response in patients with AUD would be a substantial advance in addiction medicine. We designed this study to use proteomics data as a quantitative biological trait as a step toward identifying inflammatory modulators that might be associated with acamprosate treatment outcomes. The NIAAA-funded Mayo Clinic Center for the Individualized Treatment of Alcoholism study had previously recruited 442 AUD patients who received 3 months of acamprosate treatment. However, only 267 subjects returned for the 3-month follow-up visit and, as a result, had treatment outcome information available. Baseline alcohol craving intensity was the most significant predictor of acamprosate treatment outcomes. We performed plasma proteomics using the Olink target 96 inflammation panel and identified that baseline plasma TNF superfamily member 10 (TNFSF10) concentration was associated with alcohol craving intensity and variation in acamprosate treatment outcomes among AUD patients. We also performed RNA sequencing using baseline peripheral blood mononuclear cells from AUD patients with known acamprosate treatment outcomes which revealed that inflammation-related pathways were highly associated with relapse to alcohol use during the 3 months of acamprosate treatment. These observations represent an important step toward advancing our understanding of the pathophysiology of AUD and molecular mechanisms associated with acamprosate treatment response. In conclusion, applying omics-based approaches may be a practical approach for identifying biologic markers that could potentially predict alcohol craving intensity and acamprosate treatment response.https://www.frontiersin.org/articles/10.3389/fphar.2022.986238/fullalcohol use disorderacamprosateTNFSF10proteomicsalcohol cravingtreatment outcomes |
| spellingShingle | Ming-Fen Ho Cheng Zhang Irene Moon Brandon J. Coombes Joanna Biernacka Michelle Skime Doo-Sup Choi Paul E. Croarkin Mark A. Frye Quyen Ngo Cedric Skillon Tyler S. Oesterle Victor M. Karpyak Hu Li Richard M. Weinshilboum Plasma TNFSF10 levels associated with acamprosate treatment response in patients with alcohol use disorder Frontiers in Pharmacology alcohol use disorder acamprosate TNFSF10 proteomics alcohol craving treatment outcomes |
| title | Plasma TNFSF10 levels associated with acamprosate treatment response in patients with alcohol use disorder |
| title_full | Plasma TNFSF10 levels associated with acamprosate treatment response in patients with alcohol use disorder |
| title_fullStr | Plasma TNFSF10 levels associated with acamprosate treatment response in patients with alcohol use disorder |
| title_full_unstemmed | Plasma TNFSF10 levels associated with acamprosate treatment response in patients with alcohol use disorder |
| title_short | Plasma TNFSF10 levels associated with acamprosate treatment response in patients with alcohol use disorder |
| title_sort | plasma tnfsf10 levels associated with acamprosate treatment response in patients with alcohol use disorder |
| topic | alcohol use disorder acamprosate TNFSF10 proteomics alcohol craving treatment outcomes |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.986238/full |
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