Drinking Histories in Alcohol-Use-Disordered Youth: Preliminary Findings on Relationships to Platelet Serotonin Transporter Expression With Genotypes of the Serotonin Transporter

Abstract

The serotonin (5-HT) transporter (5-HTT) is thought to play a key role in the onset of alcohol use, with potential behavioral and biological mechanisms mediated by the level of 5-HT in the synapse and in cerebral spinal fluid. Although 5-HT dysregulation has been related to poor impulse control, the biological mechanism is unknown, although functional control of the serotonergic system has been shown to be regulated in part by differential expression of the 5-HTT. The gene responsible for encoding 5-HTT has a functional polymorphism at the 5'-regulatory promoter region, which results in two forms: long (L) and short (S). The LL genotype is hypothesized to play a key role in the early onset of alcohol use and may be related to poor impulse control. The objective of this pilot study is to determine whether adolescents with a current alcohol-use disorder (AUD) (N = 21) have platelet measures of the 5-HTT functioning that are related to 5-HTT genotype and poor impulse control. Specifically, we wanted to examine the relationships between the following: platelet 5-HTT and 5-HTT genotype; platelet 5-HTT parameters and age at onset, as well as duration of drinking; and 5-HTT genotype and impulse control. Adolescents with current AUD were recruited from the community to participate in a cross-section pilot study. Our main findings showed significantly higher paroxetine binding (density of 5-HTT) in LL genotype versus S carriers (SS or SL genotypes); also, the LL group had a significantly earlier age at onset of drinking and longer duration of drinking, and poorer impulse control. These findings provide partial support for the hypothesis that, among currently drinking adolescents with an AUD, differential expression of 5-HTT may play an important role in the onset of adolescent AUD.