Can serotonin transporter genotype predict craving in alcoholism?
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.


CONCLUSIONS
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.
Department of Psychiatry and Neurobehavioral Sciences, University of Virginia, Charlottesville, Virginia 22908-0623, USA. aitdaoud@virginia.edu
Nassima
N
Ait-Daoud
John D
JD
Roache
Michael A
MA
Dawes
Lei
L
Liu
Xin-Qun
XQ
Wang
Martin A
MA
Javors
Chamindi
C
Seneviratne
Bankole A
BA
Johnson
D000328:Adult; D000367:Age Factors; D000368:Aged; D016739:Behavior, Addictive / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism*; D003463:Cues; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics* / Q000502:physiology; D014364:Tryptophan / Q000097:blood; D055815:Young Adult
D005819:Genetic Markers; D050486:Serotonin Plasma Membrane Transport Proteins; D014364:Tryptophan