title: Self-efficacy mediates the effects of topiramate and GRIK1 genotype on drinking.
abstract: Previous studies indicate that topiramate reduces alcohol use among problem drinkers, with one study showing that the effect was moderated by a polymorphism (rs2832407) in GRIK1, the gene encoding the GluK1 kainate subunit. We examined whether the interactive effect of medication and genotype (1) altered the association between daily self-efficacy and later-day drinking; and (2) had an indirect effect on drinking via self-efficacy. In a 12-week, placebo-controlled trial of topiramate, we used daily interactive voice response technology to measure self-efficacy (i.e. confidence in avoiding heavy drinking later in the day) and drinking behavior in 122 European-American heavy drinkers. Topiramate's effects on both self-efficacy and drinking level were moderated by rs2832407. C-allele homozygotes treated with topiramate showed higher levels of self-efficacy and lower levels of nighttime drinking across the 12-week trial. Further, the interactive effect of topiramate and genotype on mean nighttime drinking levels was mediated by mean levels of self-efficacy. By modeling topiramate's effects on nighttime drinking across multiple levels of analysis, we found that self-efficacy, a key psychologic construct, mediated the effect of topiramate, which was moderated by rs2832407 genotype. Thus, it may be possible to use an individualized assessment (i.e. genotype) to select treatment to optimize the reduction in heavy drinking and thereby provide a personalized treatment approach.
authors.affiliation: Center for Studies of Addiction, Department of Psychiatry, Perelman School of Medicine of the University of Pennsylvania, Philadelphia, PA, USA.|VISN4 MIRECC, Philadelphia VA Medical Center, Philadelphia, PA, USA.
authors.forename: Henry R
authors.initials: HR
authors.lastname: Kranzler
authors.affiliation: Department of Psychology, Fairleigh Dickinson University, Teaneck, NJ, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Armeli
authors.affiliation: Center for Studies of Addiction, Department of Psychiatry, Perelman School of Medicine of the University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Reagan
authors.initials: R
authors.lastname: Wetherill
authors.affiliation: Department of Medical Science, Frank Netter School of Medicine, Quinnipiac University, Hamden, CT, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Feinn
authors.affiliation: Department of Community Medicine and Healthcare, University of Connecticut School of Medicine, Farmington, CT, USA.
authors.forename: Howard
authors.initials: H
authors.lastname: Tennen
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.|Veteran Affairs Connecticut Healthcare Center, West Haven, CT, USA.
authors.forename: Joel
authors.initials: J
authors.lastname: Gelernter
authors.affiliation: Alcohol Research Center, Department of Psychiatry, University of Connecticut School of Medicine, Farmington, CT, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Covault
authors.affiliation: Center for Studies of Addiction, Department of Psychiatry, Perelman School of Medicine of the University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Timothy
authors.initials: T
authors.lastname: Pond
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000428:Alcohol Drinking / Q000235:genetics*; D000483:Alleles; D005260:Female; D005632:Fructose / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D018092:Kainic Acid Receptors / Q000235:genetics*; D020377:Self Efficacy; D000077236:Topiramate; D055815:Young Adult
chemical_list: D005632:Fructose; D018696:Neuroprotective Agents; D018092:Kainic Acid Receptors; D000077236:Topiramate
keywords: GRIK1; mediated moderation; personalized treatment; pharmacogenetics; self-efficacy; topiramate