Can serotonin transporter genotype predict craving in alcoholism?

Nassima Ait-Daoud, John D. Roache, Michael A. Dawes, Lei Liu, Xin Qun Wang, Martin A. Javors, Chamindi Seneviratne, Bankole A. Johnson

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

Background: We hypothesize that functional control of the serotonergic system is regulated in part by differential expression of the serotonin (5-HT) transporter (5-HTT). Alcohol-dependent individuals with the LL/LS genotype (L-carriers), compared with those with the SS genotype, have a lower 5-HT neurotransmission, which we hypothesize would be associated with higher craving for alcohol among L-carriers. We hypothesize further that acute peripheral depletion of tryptophan (5-HT's precursor), while further reducing 5-HT function, might decrease auto-inhibition of 5-HT neuronal firing, thereby increasing 5-HT neurotransmission transiently and lowering alcohol craving. Methods: We tested these hypotheses by examining whether in 34 Hispanic alcohol-dependent individuals subjective and physiological cue craving for alcohol differed by genotype, age of onset of problem drinking, and tryptophan availability. Results: On subjective "urge to drink" and "crave for a drink," we found a significant (p < 0.05) main effect of genotype and cue, as well as an interaction among genotype, age of onset of problem drinking, and tryptophan depletion. For the physiological measure of pulse, there was a main effect of genotype. L-carriers had higher craving than their SS counterparts, an effect that decreased under tryptophan depletion. While craving in L-carriers increased with an earlier age of onset of problem drinking, the opposite effect was seen in those with the SS genotype. Conclusion: These results not only provide support for the hypothesis that alcoholics who are L-carriers have greater alcohol craving and possibly greater propensity for drinking but also propose that there is an important 5-HTT gene-by-environment interaction that alters cue craving response for alcohol.

Original languageEnglish
Pages (from-to)1329-1335
Number of pages7
JournalAlcoholism: Clinical and Experimental Research
Volume33
Issue number8
DOIs
StatePublished - Aug 2009

Keywords

  • Alcohol Dependence
  • Cue Craving
  • Genotype
  • Serotonin Transporter
  • Tryptophan Depletion

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