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• W4293511015 endingPage "1899" @default.
• W4293511015 startingPage "1888" @default.
• W4293511015 abstract "Abstract Background The serotonin transporter (SERT) mRNA was previously reported to be a quantitative and pathophysiology‐based biomarker of heavy drinking in 5HTTLPR:LL genotype‐carriers 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). Methods Binge drinking men and women of European ancestry aged 21 to 65 years were enrolled in a 12‐day, in‐patient, randomized, double‐blind, crossover study, where they were administered three beverage doses (placebo, 0.5 g/kg [0.4 g/kg] ethanol, and 1 g/kg [0.9 g/kg] ethanol for men [women]) individually in three 4‐day periods (experiments), separated by minimum 7‐day washout period. Diet, sleep, and physical activity were controlled throughout the inpatient experiments. Twenty‐nine 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 A L A ) versus 5HTTLPR:LS/SS. Peripheral venous blood was collected daily for (1) quantification of SERT mRNA (the primary outcome measure) using qRT‐PCR and (2) plasma EtG and EtS levels using tandem mass‐spectrometry. Results The association between administered beverage dose and SERT mRNA from completers of at least one 4‐day experiment ( N = 18) 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 ( β = 5.8, SE = 1.2, p < 0.0001; β = 1.3, SE = 0.6, p = 0.023; and β = 3.0, SE = 0.7, p < 0.0001, respectively; the C ‐statistics 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 ( p = 0.0009), but not on EtG/EtS measures. Conclusion 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." @default.
• W4293511015 created "2022-08-30" @default.
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• W4293511015 date "2022-09-11" @default.
• W4293511015 modified "2023-10-17" @default.
• W4293511015 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‐blind, crossover trial" @default.
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• W4293511015 doi "https://doi.org/10.1111/acer.14931" @default.
• W4293511015 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36031718" @default.
• W4293511015 hasPublicationYear "2022" @default.
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