Can serotonin transporter genotype predict serotonergic function, chronicity, and severity of drinking?

Serotonin transporter (5-HTT) activity is greater in carriers of the long (L) vs. short (S) alleles of the 5-HTT-linked polymorphic region (5′-HTTLPR) among healthy control subjects but not alcohol-dependent adults. In 198 alcoholics, we determined the relationship between current or lifetime drinking and platelet 5-HTT function and density among allelic variants of the 5′-HTTLPR. SS subjects were younger than L-carriers (LL and LS) (p < 0.0085) and had fewer years of lifetime drinking. For L-carriers, the mean of B_max for paroxetine binding, but not V_max for serotonin (5-HT) uptake, was lower than that for SS subjects (p < 0.05). More L-carriers than their SS counterparts had V_max for 5-HT uptake below 200 nmol/10⁷ platelets-min (p < 0.05) and B_max for paroxetine binding below 600 nmol/mg protein (p < 0.06). Current drinking (drinks per day during the past 14 days) correlated positively with K_m and V_max of platelet 5-HT uptake (p < 0.05) and negatively with B_max, but not K_d, of paroxetine binding (p < 0.05) for L-carriers alone. Years of lifetime drinking correlated negatively with K_m and V_max of platelet 5-HT uptake (p < 0.05) and B_max, but not K_d, of paroxetine binding (p < 0.05) for L-carriers alone. Among L-carriers alone, there were higher levels of platelet 5-HT uptake and lower levels of platelet paroxetine binding with increased drinking, and more lifetime drinking was associated with modestly lower levels of 5-HT uptake and paroxetine binding. Thus, 5-HTT expression varies with current and lifetime drinking in L-carriers alone.