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Serotonin transporter promoter variants in autism: functional effects and relationship to platelet hyperserotonemia

Molecular Psychiatry volume 7, pages 831–836 (2002)Cite this article

Abstract

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 (Vmax and Km), uptake site densities (Bmax) 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 (Vmax) 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 Bmax values (r = 0.66, P = 0.002); correlations between uptake and platelet 5-HT levels and between Bmax 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

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Acknowledgements

Portions of this paper were presented at the Society for Neuroscience Annual Meeting, Los Angeles, CA, USA, November 7–12, 1998. We thank Laura M Hall and David M Ocame for their expert technical assistance. We gratefully acknowledge the support of the Institut National de la Santé et de la Recherche Médicale (contrat ERCA, Equipe de Recherche Clinique Associée à l'INSERM), CNRS, The French Ministry for Research & Technology, the Fondation pour la Recherche Médicale, the Société d'Etudes et de Soins pour les Enfants Paralysés et Polymalformés; as well as the NIMH (MH30929), the NICHD (HD03008), and the Korczak Foundation for Autism Research.

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Authors and Affiliations

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

    G M Anderson & D J Cohen

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

    L Gutknecht, P L Roubertoux & S Tordjman

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

    S Brailly-Tabard

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

    J H M Cohen

  5. Fondation Vallée, University Paris-Sud, France

    P Ferrari & S Tordjman

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Correspondence to G M Anderson.

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Anderson, G., Gutknecht, L., Cohen, D. et al. Serotonin transporter promoter variants in autism: functional effects and relationship to platelet hyperserotonemia. Mol Psychiatry 7, 831–836 (2002). https://doi.org/10.1038/sj.mp.4001099

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