Reduced central serotonergic activity has been implicated in poor impulse regulation and aggressive behaviour in animals, adults and also young children.(1,2) Two recently published studies have implicated variation at a polymorphism in the promoter of the serotonin transporter (5HTT; hSERT) in influencing susceptibility to ADHD.(3,4) Consistent with these results we have also found a trend for the long allele of the promoter polymorphism to influence susceptibility to ADHD in a sample of 113 ADHD parent proband trios (65 transmissions vs 49 non-transmissions, chi(2) = 2.25, P = 0.13). A pooled analysis of our, and these published results demonstrated a significant over representation of the long allele of the promoter in ADHD probands compared to controls (chi(2) = 7.14, P = 0.008). We have also examined two other 5HTT polymorphisms (the VNTR in intron 2 and the 3' UTR SNP). TDT analysis demonstrated preferential transmission of the T allele of the 3' UTR SNP (chi(2) = 4.06, P = 0.04). In addition, ETDT analysis of haplotypes demonstrated significant preferential transmission of haplotypes containing the T allele of the 3' UTR SNP with the long allele of the promoter polymorphism (chi(2) = 13.18, 3 df, P = 0.004) and the 10 repeat of the VNTR (chi(2) = 8.77, 3 df, P = 0.03). This study provides further evidence for the possible involvement of the serotonin transporter in susceptibility to ADHD.
- association study