¹Dept of Child Psychiatry, Yale University School of Medicine, New Haven, CT, USA

²FRE 2134 CNRS Genetics, Neurogenetics, Behavior, 3 B Férollerie Street, Orléans cedex 2, France

³Laboratoire d'Hormonologie et de Biologie Moléculaire, CHU de Bicêtre, France

⁴UFR Medecine ifr 53 pôle Biomolecule, Equipe Physiopathologie Dysimmunitaire Humaine, EA 3309, URCA, Reims, France

⁵Fondation Vallée, University Paris-Sud, France

Correspondence to: G M Anderson, PhD, Yale Child Study Center, 230 S Frontage Rd, New Haven, CT 06510, USA. E-mail: george.anderson@yale.edu

The well-replicated platelet hyperserotonemia of autism has stimulated interest in serotonin (5-HT) in autism. We have examined the effects of the serotonin transporter gene (5-HTT, locus SLC6A4) promoter polymorphism (5-HTTLPR) on platelet 5-HT physiology in autism. Platelet 5-HT uptake rates and affinities (V_max and K_m), uptake site densities (B_max) and 5-HT levels were examined in 31 French individuals with autism genotyped with respect to the 5-HTTLPR. Platelet 5-HT uptake and 5-HT levels were measured using HPLC; uptake sites were determined by radioligand binding. A 1.5-fold increased rate (V_max) of platelet 5-HT uptake was observed in ll genotype individuals compared to those with ls and ss genotypes (Mann- Whitney U-test, P = 0.022). However, no significant relationship was observed between genotype and uptake site density (U-test, P = 0.51). Although median levels of platelet 5-HT in platelet-rich plasma were higher in the ll group, only trend level significance was observed (U-test, P= 0.069); platelet 5-HT content measured in whole blood was similar across genotypes. Uptake rates were well correlated with B_max values (r = 0.66, P = 0.002); correlations between uptake and platelet 5-HT levels and between B_max values and 5-HT levels were somewhat lower. While 5-HTTLPR alleles had an appreciable effect on platelet 5-HT uptake rates, effects on 5-HT levels and uptake site density were smaller or absent. Based on these preliminary data and prior studies of allele frequencies, we conclude that the 5-HTTLPR is not a major determinant of the group mean platelet serotonin elevation seen in autism. However, a role for increased uptake in the hyperserotonemia of autism can not be ruled out. In addition, it appears that studies of platelet 5-HT measures in autism and other disorders should take account of the effects of 5-HTTLPR genotype on 5-HT uptake

Molecular Psychiatry (2002) 7, 831-836. doi:10.1038/sj.mp.4001099

serotonin transporter; platelet 5-HT uptake; autism; platelet hyperserotonemia; 5-HTTLPR; SLC6A4 locus