Serotonin transporter promoter polymorphism genotype is associated with behavioral disinhibition and negative affect in children of alcoholics

Background: Serotonergic (5-HT) dysfunction has been implicated in the etio logy of both behavioral disinhibition (BD) and negative affect (NA). This w ork extends our previous finding of relationships between whole blood 5-HT and both BD and NA in pubescent, but not prepubescent, children of alcoholi cs and continues examination of a hypothesized role of 5-HT dysfunction in alcoholism risk. The long and short (L and S) variants of the 5-HT transpor ter gene-linked polymorphic region (5-HTTLPR) are responsible for differing transcriptional efficiencies in 5-HT uptake. Although associations have be en found between the SS 5-HTTLPR genotype and severe alcoholism and neuroti cism, recent reports describe relationships between the LL genotype and bot h low level of response to alcohol and alcoholism diagnosis and a predomina nce of the LL genotype in early-onset alcoholics. Methods: This report is from an ongoing prospective study of the developmen t of risk for alcoholism and other problematic outcomes in a sample of fami lies classified by father's alcoholism subtype. This study examines relatio nships between 5-HTTLPR genotype and both child ED (Child Behavior Checklis t Ag gressive Behavior) and NA (Child Behavior Checklist Anxious/Depressed) in offspring from 47 families. Results: Results showed significantly higher levels of ED and NA in the 16 children with the LL genotype than the 46 SS or SL children. Conclusions: Behaviors of undercontrol, which occur at increased rates in c hildren of alcoholics, may be genetically influenced through the regulation of the 5-HT transporter. Due to the small sample size and the preliminary nature of our findings, replication is necessary.