{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T00:33:25Z","timestamp":1747182805816,"version":"3.40.5"},"reference-count":68,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2022,9,11]],"date-time":"2022-09-11T00:00:00Z","timestamp":1662854400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000027","name":"National Institute on Alcohol Abuse and Alcoholism","doi-asserted-by":"publisher","award":["K23AA020899","R01AA026291"],"award-info":[{"award-number":["K23AA020899","R01AA026291"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alcoholism Clin &amp;amp; Exp Res"],"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The serotonin transporter (SERT) mRNA was previously reported to be a quantitative and pathophysiology\u2010based biomarker of heavy drinking in 5HTTLPR:LL genotype\u2010carriers treated with ondansetron. Here, we validated the potential use of SERT mRNA for quantitative prediction of recent alcohol consumption (in the absence of treatment) and compared it with the known biomarkers ethyl glucuronide (EtG) and ethyl sulfate (EtS).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Binge drinking men and women of European ancestry aged 21 to 65\u2009years were enrolled in a 12\u2010day, in\u2010patient, randomized, double\u2010blind, crossover study, where they were administered three beverage doses (placebo, 0.5\u00a0g\/kg [0.4\u00a0g\/kg] ethanol, and 1\u00a0g\/kg [0.9\u00a0g\/kg] ethanol for men [women]) individually in three 4\u2010day periods (experiments), separated by minimum 7\u2010day washout period. Diet, sleep, and physical activity were controlled throughout the inpatient experiments. Twenty\u2010nine participants were randomized to receive beverage doses counterbalancing the sequence of treatment and gender within subgroups stratified by SERT genotypes 5HTTLPR:LL+rs25531:AA (L<jats:sub>A<\/jats:sub>L<jats:sub>A<\/jats:sub>) versus 5HTTLPR:LS\/SS. Peripheral venous blood was collected daily for (1) quantification of SERT mRNA (the primary outcome measure) using qRT\u2010PCR and (2) plasma EtG and EtS levels using tandem mass\u2010spectrometry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The association between administered beverage dose and SERT mRNA from completers of at least one 4\u2010day experiment (<jats:italic>N<\/jats:italic>\u00a0=\u200918) assessed by a linear mixed model was not statistically significant. Significant positive associations were found with beverage dose and plasma EtG, EtS and EtG\/EtS ratio (<jats:italic>\u03b2<\/jats:italic>\u00a0=\u20095.8, SE\u00a0=\u00a01.2, <jats:italic>p<\/jats:italic>\u00a0&lt;\u20090.0001; <jats:italic>\u03b2<\/jats:italic>\u00a0=\u20091.3, SE\u00a0=\u00a00.6, <jats:italic>p<\/jats:italic>\u00a0=\u20090.023; and <jats:italic>\u03b2<\/jats:italic>\u00a0=\u20093.0, SE\u00a0=\u00a00.7, <jats:italic>p<\/jats:italic>\u00a0&lt;\u20090.0001, respectively; the <jats:italic>C<\/jats:italic>\u2010statistics for discriminating outcomes were 0.97, 0.8, and 0.92, respectively). Additionally, we observed a sequence effect with a greater placebo effect on SERT mRNA when it was administered during the first experiment (<jats:italic>p<\/jats:italic>\u00a0=\u20090.0009), but not on EtG\/EtS measures.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The findings do not validate the use of SERT as a biomarker of heavy drinking. Larger and more innovative studies addressing the effects of placebo, race, gender, and response to treatment with serotonergic agents are needed to fully assess the utility of SERT as a biomarker of heavy and binge drinking.<\/jats:p><\/jats:sec>","DOI":"10.1111\/acer.14931","type":"journal-article","created":{"date-parts":[[2022,8,29]],"date-time":"2022-08-29T04:04:51Z","timestamp":1661745891000},"page":"1888-1899","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Validation of serotonin transporter <scp>mRNA<\/scp> as a quantitative biomarker of heavy drinking and its comparison to ethyl glucuronide\/ethyl sulfate: A randomized, double\u2010blind, crossover trial"],"prefix":"10.1111","volume":"46","author":[{"given":"Jessica","family":"Cornell","sequence":"first","affiliation":[{"name":"Department of Psychiatry University of Maryland School of Medicine  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew","family":"Conchas","sequence":"additional","affiliation":[{"name":"AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research  Frederick Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin\u2010Qun","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Public Health Sciences University of Virginia  Charlottesville Virginia USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey C.","family":"Fink","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Maryland School of Medicine  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hegang","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Epidemiology University of Maryland School of Medicine  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maureen A.","family":"Kane","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences University of Maryland School of Pharmacy  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nageswara","family":"Pilli","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences University of Maryland School of Pharmacy  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nassima","family":"Ait\u2010Daoud","sequence":"additional","affiliation":[{"name":"Department of Psychiatry University of Virginia  Charlottesville Virginia USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David A.","family":"Gorelick","sequence":"additional","affiliation":[{"name":"Department of Psychiatry University of Maryland School of Medicine  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ming D.","family":"Li","sequence":"additional","affiliation":[{"name":"Seton Hall University  South Orange New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bankole A.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Department of Psychiatry University of Maryland School of Medicine  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3135-2979","authenticated-orcid":false,"given":"Chamindi","family":"Seneviratne","sequence":"additional","affiliation":[{"name":"Department of Psychiatry University of Maryland School of Medicine  Baltimore Maryland USA"},{"name":"The Institute for Genome Sciences University of Maryland School of Medicine  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,9,11]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11469-017-9769-4"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdr2.1427"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2019.00091"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1101\/238873"},{"key":"e_1_2_9_6_1","unstructured":"Bloomberg. 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