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

Molecular Psychiatry volume 6, pages 434–439 (2001)Cite this article

Abstract

The promoter polymorphism of the serotonin transporter gene (HTT, locus SLC6A4) is of special interest in autism given the well-replicated platelet hyperserotonemia of autism, treatment effects of serotonin reuptake inhibitors, and the role of serotonin in limbic functioning and neurodevelopment. Parent-offspring transmission of the long (l) and short (s) alleles of the deletion/insertion polymorphism in the HTT promoter region was examined in families of 71 children with autism using the transmission test for linkage disequilibrium (TDT). Transmission of HTT promoter alleles did not differ between 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 severely impaired individuals and greater l transmission in mild/moderately impaired individuals. This relationship between HTT promoter alleles and severity of autistic impairment was also seen when ratings of social and communication behaviors were compared across genotypes. The data indicate that HTT 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 assess each of the major behavioral domains and seriously consider the possible role of modifying loci.

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Acknowledgements

We thank Richard Spielman for his helpful comments. This work was supported in France by the Institut National de la Santé et de la Recherche Médicale (contrat Equipe de Recherche Clinique Associée à I'Institut National de la Santé et de la Recherche Médicale), the Centre National de la Recherche Scientifique (Formation de Recherche en Evolution 2134), the Ministère de I'Education Nationale, de la Recherche et de la Technologie, the Conseil de la Région Centre. Support in the USA was provided by the National Institute of Mental Health (MH30929) and the National Institute of Child Health and Human Development (HD03008), and the Korczak Foundation for Autism Research.

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Authors and Affiliations

  1. FRE 2134 CNRS Genetics Neurogenetics and Behavior, 3B Férollerie Street, Orléans, 45071, cedex 2, France

    S Tordjman, L Gutknecht, M Carlier, E Spitz, F Slama & P L Roubertoux

  2. Fondation Vallée, University of Paris-Sud, 7 rue Bensérade, Gentilly, 94257, cedex, France

    S Tordjman, C Antoine, V Carsalade & P Ferrari

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

    D J Cohen & G M Anderson

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  1. S Tordjman
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  2. L Gutknecht
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Correspondence to S Tordjman.

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Tordjman, S., Gutknecht, L., Carlier, M. et al. Role of the serotonin transporter gene in the behavioral expression of autism. Mol Psychiatry 6, 434–439 (2001). https://doi.org/10.1038/sj.mp.4000873

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  • DOI: https://doi.org/10.1038/sj.mp.4000873

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