Original Research ARTICLE
Serotonin transporter genomic biomarker for quantitative assessment of ondansetron treatment response in alcoholics
- Department of Psychiatry and Neurobehavioral Sciences, University of Virginia, Charlottesville, VA, USA
Paucity of sensitive biomarkers to quantify transient changes in alcohol consumption level remains a critical barrier for the development of efficacious therapeutic agents to treat alcoholism. Recently, in an 11-week, randomized, placebo-controlled, double-blind trial of 283 alcohol-dependent individuals, we demonstrated that ondansetron was efficacious at reducing the severity of drinking (measured as drinks per drinking day; DDD) in alcoholics carrying the LL compared with the LS/SS genotype of the serotonin transporter gene, 5′-HTTLPR. Using peripheral blood samples from a cohort of 41 of these subjects, we determined whether there was a relationship between mRNA expression level of the 5′-HTTLPR genotypes (measured at weeks 0, 4, and 11) and self-reported alcohol consumption following treatment with either ondansetron (4 μg/kg twice daily; N = 19) or placebo (N = 22). Using a mixed-effects linear regression model, we analyzed the effects of DDD and 5′-HTTLPR genotypes on mRNA expression levels within and between the ondansetron and placebo groups. We found a significant three-way interaction effect of DDD, 5′-HTTLPR genotypes, and treatment on mRNA expression levels (p = 0.0396). Among ondansetron but not placebo recipients, there was a significant interaction between DDD and 5′-HTTLPR genotype (p = 0.0385 and p = 0.7938, respectively). In the ondansetron group, DDD was associated positively with mRNA levels at a greater rate of expression alteration per standard drink in those with the LL genotype (slope = +1.1698 in ln scale). We suggest that the combination of the LL genotype and 5′-HTTLPR mRNA expression levels might be a promising and novel biomarker to quantify drinking severity in alcoholics treated with ondansetron.
Keywords: 5′-HTTLPR, genotype, mRNA, biomarker, alcohol, ondansetron, pharmacogenetic, serotonin
Citation: Seneviratne C and Johnson BA (2012) Serotonin transporter genomic biomarker for quantitative assessment of ondansetron treatment response in alcoholics. Front. Psychiatry 3:23. doi: 10.3389/fpsyt.2012.00023
Received: 13 August 2011; Accepted: 04 March 2012;
Published online: 28 March 2012.
Edited by:Margit Burmeister, University of Michigan, USA
Reviewed by:Herb Lachman, Albert Einstein College of Medicine of Yeshiva University, USA
Michael E. Zwick, Emory University, USA
Copyright: © 2012 Seneviratne and Johnson. This is an open-access article distributed under the terms of the Creative Commons Attribution Non Commercial License, which permits non-commercial use, distribution, and reproduction in other forums, provided the original authors and source are credited.
*Correspondence: Bankole A. Johnson, Department of Psychiatry and Neurobehavioral Sciences, University of Virginia, P.O. Box 800623, Charlottesville, VA 22908-0623, USA. e-mail: firstname.lastname@example.org