Family-based association study of serotonergic candidate genes and attention-deficit/hyperactivity disorder in a...

Alterations in the serotonergic pathway have been implicated in the pathogenesis of attention-deficit/hyperactivity disorder (ADHD). The aim of this study was to investigate seven genetic variants in three genes (serotonin transporter (5-HTT), serotonin receptor 1B (5-HTR1B) and serotonin receptor 2A (5-HTR2A)), which have previously been shown to be associated with ADHD. The polymorphisms under investigation were the 5-HTTLPR, the VNTR in intron 2 and the 3'UTR SNP in 5-HTT, the 5-HTR1B variations 861G>C and 102T>C, and the 5-HTR2A variations His452Tyr and 1438G>A. We genotyped these variants in a sample of 102 families with 229 children with ADHD according to DSM-IV criteria. Among the affected children, 69% fulfilled criteria for the combined type, 27% for the predominantly inattentive type, and 4% for the predominantly hyperactive-impulsive type. Associations were tested by the pedigree transmission disequilibrium test (PDT). All investigated polymorphisms in serotonergic candidate genes showed no association to ADHD in our sample. Earlier studies of these polymorphisms had also shown inconsistent results, with some studies reporting significant associations and others demonstrating no association. This discordance between studies may reflect variation in patient ascertainment criteria, genetic heterogeneity, too low statistical power for the expected effects or false positive results in the initial reports. We cannot rule out the possibility that other variations in the investigated genes contribute to the etiology of ADHD.