title: 5-HTTLPR genotype and daily negative mood moderate the effects of sertraline on drinking intensity.
abstract: We previously reported moderating effects of age of onset of alcohol dependence (AD) and a functional polymorphism (5-HTTLPR) in the gene encoding the serotonin transporter protein in a sample of 134 individuals participating in a 12-week, placebo-controlled trial of sertraline. To understand more fully the effects seen in that study, we examined moderation by negative moods reported each evening, with nighttime drinking intensity (i.e. the number of standard drinks consumed at night) as the dependent variable. We found a daily anxiety × age of onset × 5-HTTLPR polymorphism × medication interaction, which reflected a daily anxiety × medication group effect for early-onset individuals homozygous for the high-expression (L') allele, but not others. Specifically, on days characterized by relatively high levels of anxiety, early-onset L' homozygotes receiving placebo reduced their drinking intensity significantly. In contrast, early-onset L' homozygotes treated with sertraline non-significantly increased their drinking intensity. These findings implicate anxiety as a key moderator of the observed pharmacogenetic effects. These findings have important implications because of the high prevalence of AD and the frequency with which SSRIs are prescribed to treat the disorders.
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 VAMC, Philadelphia, PA, USA.
authors.forename: Henry R
authors.initials: HR
authors.lastname: Kranzler
authors.forename: Stephen
authors.initials: S
authors.lastname: Armeli
authors.forename: Howard
authors.initials: H
authors.lastname: Tennen
authors.forename: Jonathan
authors.initials: J
authors.lastname: Covault
mesh_terms: D000293:Adolescent; D000328:Adult; D000339:Affect; D017668:Age of Onset; D000368:Aged; D000428:Alcohol Drinking / Q000188:drug therapy / Q000235:genetics / Q000523:psychology; D000434:Alcoholic Beverages / Q000706:statistics & numerical data; D000437:Alcoholism / Q000188:drug therapy / Q000235:genetics / Q000523:psychology; D000483:Alleles; D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001007:Anxiety / Q000235:genetics*; D004311:Double-Blind Method; D005260:Female; D005838:Genotype; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D010919:Placebos; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D020280:Sertraline / Q000494:pharmacology / Q000627:therapeutic use*; D013997:Time Factors; D055815:Young Adult
chemical_list: D000928:Antidepressive Agents; D010919:Placebos; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D020280:Sertraline
keywords: 5-HTTLPR; SSRI; alcohol dependence