Role of the serotonin transporter gene in the behavioral expression of autism
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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There is a male prevalence in autism, about three to four times higher in males than in females.
“It is noteworthy that there is a male prevalence in autism [about three to four times higher in males than in females (21)], which might also fit with greater social communication difficulties observed in males compared to females with typical development.”
From Gene × Environment Interactions in Autism Spectrum Disorders: Role of Epigenetic Mechanisms (2014) · cites this paper as [21]
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- Authors
- Tordjman, S., Gutknecht, L., Carlier, M., Spitz, E., Antoine, C., Slama, F., Carsalade, V, Cohen, D. J., Ferrari, P., Roubertoux, P. L., & Anderson, G. M.
- Affiliations
- Université Paris-Sud (FR)
- Centre National de la Recherche Scientifique (FR)
- Yale University (US)
- Corresponding author
- Tordjman, S
- Venue
- Molecular Psychiatry
- Published
- 2001-07-01
- Volume
- 6
- Issue
- 4
- Pages
- 434-439
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- OpenAlex
- W2123530751
- Cited by
- 196
- References
- 39
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2023: 4 · 2022: 4 · 2021: 4 · 2020: 5 · 2019: 5 · 2018: 4 · 2017: 7 · 2016: 4 · 2015: 5 · 2014: 9 · 2013: 5 · 2012: 7
- FWCI
- 7.86
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Institut National de la Santé et de la Recherche Médicale
- Centre National de la Recherche Scientifique
- National Institutes of Health
- National Institute of Mental Health (MH30929)
- National Institute of Child Health and Human Development
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD03008, P01HD003008)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- autism spectrum disorder, serotonin transporter gene, serotonin transporter, promoter polymorphism, allele transmission, autism severity, linkage disequilibrium, serotonin, serotonin reuptake inhibitors
- MeSH terms
- Adolescent, Adult, Autistic Disorder, Carrier Proteins, Child, Child, Preschool, Chromosome Mapping, DNA Transposable Elements, Fathers, Female, France, Genotype, Genetic Carrier Screening, Humans, Male, Membrane Glycoproteins, Mothers, Nerve Tissue Proteins, Nuclear Family, Polymorphism, Genetic, Promoter Regions, Genetic, Wechsler Scales, Sequence Deletion, Genetic Predisposition to Disease, Membrane Transport Proteins, White People, Serotonin Plasma Membrane Transport Proteins
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