The serotonin (5-hydroxytryptamine: 5-HT) system has been thought to play an important role in several steps of alcohol craving. A number of studies, including our own, have reported that alcohol dependence is associated with dysfunction of 5-HT transmission. Pharmacological and clinical studies have shown that the 5-HT transporter (5-HTT) and the 5-HT1A receptor appear to be candidate loci for the aetiology of alcohol dependence. We have analysed the presence of different 5-HTT and 5-HT1A variants in 104 alcohol-dependent patients and 38 controls for a possible association with alcohol dependence. In alcohol-dependent patients, we found a high frequency of the S allele of 5-HTTLPR (45.5% vs. 29%, χ2 = 6.33, p = 0.0081). No other significant differences were observed between the two populations for other polymorphisms. These results provide, for the first time, preliminary evidence that alcohol abuse disorders are associated with a genetic variant for 5-HT transmission. It might be possible to use this detection of the “S” allele as a clinical tool for pathology diagnosis and to advise recovering alcoholics and it could represent an aid to the prevention of relapse. Therapeutic actions could be envisaged to use this genotyping to help select the best therapeutic strategy.

We studied platelet 3H-serotonin uptake in 32 former alcoholics, withdrawn for from 1 month to 22 years, in their descendants ( 21.7+/-1.6 years old, n=17; 10.9 0.7 years old; n=19), and in respective control groups, paired in age and sex. All of the alcoholics presented high 3H-serotonin uptake (Vmax=10.88+/-4.23 pmoles/10(8)pl/30sec.,vs. 0.93+/-0.15pmole/10(8)pl/30sec. Their descendants also showed high platelet serotonin uptake: 3.94+/-1.44 pmoles/10(8)pl/30sec., vs. 0.93+/-0.15 pmoles/10(8)pl/30sec. for adult descendants, and 5.99+/-2.23 vs. 0.84+/-0.15 pmole/10(8)pl/30 sec. for young descendants. All subjects were free of alcoholisation ( biological parameters studied were blood ethanol concentration, gamma glutamyl transferase and mean corpuscular volume), and dependence of former alcoholics was evaluate by using, a posteriori, the CAGE test. In descendants, 28% of the subjects have Vmax values higher than the highest of the control group. Alcohol, in vitro, (54 mM) did not affect serotonin uptake in any group. These results indicate that in descendants of alcoholics, platelet serotonin uptake is altered, without modification of sensitivity to ethanol. The genetic basis of alcohol dependence could be linked with the platelet serotonin transport.