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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.

SUBMITTER: Kranzler HR

PROVIDER: S-EPMC3578002 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

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5-HTTLPR genotype and daily negative mood moderate the effects of sertraline on drinking intensity.

Kranzler Henry R HR Armeli Stephen S Tennen Howard H Covault Jonathan J

Addiction biology 20121112 6

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 dep ...[more]

PMID: 23145795

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Project description:The purpose of this exploratory study was to examine the interaction of 5-HTTLPR and DRD4 exon III polymorphisms with gender in non-treatment seeking alcohol-dependent (AD) individuals while alternately taking ondansetron and sertraline. Evidence suggests that alcohol dependence may be influenced by a genetic interaction that may be gender-specific with temporal changes making pharmacological treatment with serotonergic drugs complex. The main trial was a within-subject double-blind placebo-controlled human laboratory study with 77 non-treatment-seeking AD individuals randomized (55 completed, 49 complete data) to receive 200 mg/day of sertraline or 0.5 mg/day of ondansetron for 3 weeks followed by an alcohol self-administration experiment (ASAE), then placebo for 3 weeks followed by a second ASAE, then receive the alternate drug, in a counterbalanced order, for 3 weeks followed by a third ASAE. Results for men were not significant. Women with the LL 5-HTTLPR genotype receiving ondansetron and SS/SL 5-HTTLPR genotype receiving sertraline (matched), drank significantly fewer drinks per drinking day (DDD) during the 7 days prior to the first and third ASAEs than women receiving the mismatched medication (i.e., sertraline to LL and ondansetron to SS/SL). In a 3-way interaction, 5-HTTLPR alleles by DRD4 alleles by medications, women with the LL genotype who received ondansetron and had DRD4?7 exon III repeats drank significantly fewer DDD as did SS/SL women who received sertraline but conversely had DRD4<7 repeats in the 7-day period leading up to the first and third ASAEs. Consistent with these data was a significant reduction of milliliters consumed ad libitum during these same ASAEs. These exploratory findings add possible support to gender and genetic differences among AD individuals in response to serotonergic pharmacotherapies. Future trials should be powerful enough to take into account that endophenotypes and a targeting of serotonergic interactions may be essential to successfully treat alcohol dependence.

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5-HTTLPR genotype and daily negative mood moderate the effects of sertraline on drinking intensity.

Publications

5-HTTLPR genotype and daily negative mood moderate the effects of sertraline on drinking intensity.

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