{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T04:00:00Z","timestamp":1780977600475,"version":"3.54.1"},"reference-count":51,"publisher":"Wiley","issue":"13","license":[{"start":{"date-parts":[[2022,2,8]],"date-time":"2022-02-08T00:00:00Z","timestamp":1644278400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2022,2,8]],"date-time":"2022-02-08T00:00:00Z","timestamp":1644278400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R01GM28157"],"award-info":[{"award-number":["R01GM28157"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["U19 GM61388"],"award-info":[{"award-number":["U19 GM61388"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000027","name":"National Institute on Alcohol Abuse and Alcoholism","doi-asserted-by":"publisher","award":["P20 AA17830"],"award-info":[{"award-number":["P20 AA17830"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000027","name":"National Institute on Alcohol Abuse and Alcoholism","doi-asserted-by":"publisher","award":["R21 AA25214"],"award-info":[{"award-number":["R21 AA25214"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000027","name":"National Institute on Alcohol Abuse and Alcoholism","doi-asserted-by":"publisher","award":["R01 AA27486"],"award-info":[{"award-number":["R01 AA27486"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000027","name":"National Institute on Alcohol Abuse and Alcoholism","doi-asserted-by":"publisher","award":["U01 AA27487"],"award-info":[{"award-number":["U01 AA27487"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000027","name":"National Institute on Alcohol Abuse and Alcoholism","doi-asserted-by":"publisher","award":["K01 AA28050"],"award-info":[{"award-number":["K01 AA28050"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["UL1TR000135"],"award-info":[{"award-number":["UL1TR000135"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2022,7]]},"abstract":"<jats:sec>\n                    <jats:title>Background and Purpose<\/jats:title>\n                    <jats:p>Acamprosate is an anti\u2010craving drug used for the pharmacotherapy of alcohol use disorder (AUD). However, only some patients achieve optimal therapeutic outcomes. This study was designed to explore differences in metabolomic profiles between patients who maintained sobriety and those who relapsed, to determine whether those differences provide insight into variation in acamprosate treatment response phenotypes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>We previously conducted an acamprosate trial involving 442 AUD patients, and 267 of these subjects presented themselves for a 3\u2010month follow\u2010up. The primary outcome was abstinence. Clinical information, genomic data and metabolomics data were collected. Baseline plasma samples were assayed using targeted metabolomics.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>Baseline plasma arginine, threonine, \u03b1\u2010aminoadipic acid and ethanolamine concentrations were associated with acamprosate treatment outcomes and baseline craving intensity, a measure that has been associated with acamprosate treatment response. We next applied a pharmacometabolomics\u2010informed genome\u2010wide association study (GWAS) strategy to identify genetic variants that might contribute to variations in plasma metabolomic profiles that were associated with craving and\/or acamprosate treatment outcome. Gene expression data for induced pluripotent stem cell\u2010derived forebrain astrocytes showed that a series of genes identified during the metabolomics\u2010informed GWAS were ethanol responsive. Furthermore, a large number of those genes could be regulated by acamprosate. Finally, we identified a series of single nucleotide polymorphisms that were associated with acamprosate treatment outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion and Implications<\/jats:title>\n                    <jats:p>These results serve as an important step towards advancing our understanding of disease pathophysiology and drug action responsible for variation in acamprosate response and alcohol craving in AUD patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.15795","type":"journal-article","created":{"date-parts":[[2022,1,11]],"date-time":"2022-01-11T19:44:54Z","timestamp":1641930294000},"page":"3330-3345","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Genetic variants associated with acamprosate treatment response in alcohol use disorder patients: A multiple omics study"],"prefix":"10.1111","volume":"179","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3757-3924","authenticated-orcid":false,"given":"Ming\u2010Fen","family":"Ho","sequence":"first","affiliation":[{"name":"Department of Molecular Pharmacology and Experimental Therapeutics Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Molecular Pharmacology and Experimental Therapeutics Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lixuan","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Molecular Pharmacology and Experimental Therapeutics Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingxin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Molecular Pharmacology and Experimental Therapeutics Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Moon","sequence":"additional","affiliation":[{"name":"Department of Molecular Pharmacology and Experimental Therapeutics Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer R.","family":"Geske","sequence":"additional","affiliation":[{"name":"Department of Health Sciences Research, Division of Biomedical Statistics and Informatics Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle K.","family":"Skime","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychology Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doo\u2010Sup","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Molecular Pharmacology and Experimental Therapeutics Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna M.","family":"Biernacka","sequence":"additional","affiliation":[{"name":"Department of Health Sciences Research, Division of Biomedical Statistics and Informatics Mayo Clinic  Rochester Minnesota USA"},{"name":"Department of Psychiatry and Psychology Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tyler S.","family":"Oesterle","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychology Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark A.","family":"Frye","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychology Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marvin D.","family":"Seppala","sequence":"additional","affiliation":[{"name":"Hazelden Betty Ford Foundation  Center City Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor M.","family":"Karpyak","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychology Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hu","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Molecular Pharmacology and Experimental Therapeutics Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard M.","family":"Weinshilboum","sequence":"additional","affiliation":[{"name":"Department of Molecular Pharmacology and Experimental Therapeutics Mayo Clinic  Rochester Minnesota USA"},{"name":"Center for Individualized Medicine Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,2,8]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14748"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14112"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.295.17.2003"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41386-021-01097-0"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/alcalc\/agaa071"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2005.06.015"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1080\/00952990.2017.1286500"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)31775-1"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drugalcdep.2020.108002"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.m3934"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14153"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drugalcdep.2015.08.023"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.15288\/jsa.2003.64.120"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/JCP.0000000000000590"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/acer.13131"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamapsychiatry.2015.0584"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.61.8.807"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2016.6"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-009-1515-6"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-02442-4"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-020-0855-9"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2020.01.141"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.12348"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/tp.2014.103"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drugalcdep.2018.12.010"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amepre.2019.12.015"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/acer.14233"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-017-0056-8"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-018-0307-5"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2017.282"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0893-133X(02)00368-8"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.2011.01616.x"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/add.13311"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1002215"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/tp.2015.120"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1017\/neu.2015.70"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2012.05.015"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2017.152"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1521-0391.2012.00297.x"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/npr2.12028"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1093\/alcalc\/agy093"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1111\/add.12238"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.1097\/HRP.0000000000000079"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.65.3.345"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1720446115"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.1093\/alcalc\/agg075"},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-019-0363-y"},{"key":"e_1_2_12_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-019-0377-5"},{"key":"e_1_2_12_50_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-004-1991-7"},{"key":"e_1_2_12_51_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aax4043"},{"key":"e_1_2_12_52_1","doi-asserted-by":"publisher","DOI":"10.1111\/acer.13491"}],"container-title":["British Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bph.15795","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/bph.15795","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bph.15795","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T03:20:44Z","timestamp":1780975244000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/bph.15795"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,8]]},"references-count":51,"journal-issue":{"issue":"13","published-print":{"date-parts":[[2022,7]]}},"alternative-id":["10.1111\/bph.15795"],"URL":"https:\/\/doi.org\/10.1111\/bph.15795","archive":["Portico"],"relation":{},"ISSN":["0007-1188","1476-5381"],"issn-type":[{"value":"0007-1188","type":"print"},{"value":"1476-5381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,8]]},"assertion":[{"value":"2021-03-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-01-07","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-02-08","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}