Can Serotonin Transporter Genotype Predict Craving in Alcoholism?
Article first published online: 4 MAY 2009
Copyright © 2009 by the Research Society on Alcoholism
Alcoholism: Clinical and Experimental Research
Volume 33, Issue 8, pages 1329–1335, August 2009
How to Cite
Ait-Daoud, N., Roache, J. D., Dawes, M. A., Liu, L., Wang, X.-Q., Javors, M. A., Seneviratne, C. and Johnson, B. A. (2009), Can Serotonin Transporter Genotype Predict Craving in Alcoholism?. Alcoholism: Clinical and Experimental Research, 33: 1329–1335. doi: 10.1111/j.1530-0277.2009.00962.x
- Issue published online: 27 JUL 2009
- Article first published online: 4 MAY 2009
- Received for publication October 21, 2008; accepted March 3, 2009.
- Alcohol Dependence;
- Serotonin Transporter;
- Cue Craving;
- Tryptophan Depletion
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.