Role of the serotonin transporter gene in the behavioral expression of autism

The promoter polymorphism of the serotonin transporter gene (HTT, locus SLC 6A4) is of special interest in autism given the well-replicated platelet hy perserotonemia of autism, treatment effects of serotonin reuptake inhibitor s, and the role of serotonin in limbic functioning and neurodevelopment. Pa rent-offspring transmission of the long (l) and short (s) alleles of the de letion/insertion polymorphism in the HTT promoter region was examined in fa milies of 71 children with autism using the transmission test for linkage d isequilibrium (TDT). Transmission of HTT promoter alleles did not differ be tween probands with autism and their unaffected siblings. However, allelic transmission in probands was dependent upon severity of impairments in the social and communication domains, with greater s allele transmission in sev erely impaired individuals and greater I transmission in mild/moderately im paired individuals. This relationship between HTT promoter alleles and seve rity of autistic impairment was also seen when ratings of social and commun ication behaviors were compared across genotypes. The data indicate that HT T promoter alleles by themselves do not convey risk for autism, but, rather , modify the severity of autistic behaviors in the social and communication domains. The results require replication and, given the size of the groups and subgroups examined, must be considered still preliminary. The results suggest that future research on the genetics of autism should carefully ass ess each of the major behavioral domains and seriously consider the possibl e role of modifying loci.