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Brief Report: Glutamate Transporter Gene (SLC1A1) Single Nucleotide Polymorphism (rs301430) and Repetitive Behaviors and Anxiety in Children with Autism Spectrum Disorder

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Abstract

Investigated association of single nucleotide polymorphism (SNP) rs301430 in glutamate transporter gene (SLC1A1) with severity of repetitive behaviors (obsessive–compulsive behaviors, tics) and anxiety in children with autism spectrum disorder (ASD). Mothers and/or teachers completed a validated DSM-IV-referenced rating scale for 67 children with autism spectrum disorder. Although analyses were not significant for repetitive behaviors, youths homozygous for the high expressing C allele had more severe anxiety than carriers of the T allele. Allelic variation in SLC1A1 may be a biomarker for or modifier of anxiety symptom severity in children with ASD, but study findings are best conceptualized as tentative pending replication with larger independent samples.

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References

  • Arnold, P. D., Sicard, T., Burroughs, E., Richter, M. A., & Kennedy, J. L. (2006). Glutamate transporter gene SLC1A1 associated with obsessive-compulsive disorder. Archives of General Psychiatry, 63, 769–776.

    Article  PubMed  Google Scholar 

  • Belsky, J., Jonassaint, C., Pluess, M., Stanton, M., Brummett, B., & Williams, R. (2009). Vulnerability genes or plasticity genes. Molecular Genetics, 14, 746–754.

    Google Scholar 

  • Billstedt, E., Gillberg, I. C., & Gillberg, C. (2007). Autism in adult: Symptom patterns and early childhood predictors. Journal of Child Psychology and Psychiatry, 48, 1102–1110.

    Article  PubMed  Google Scholar 

  • Bishop, S. L., Richler, J., Cain, A. C., & Lord, C. (2007). Predictors of perceived negative impact in moterhs of children with autism spectrum disorder. American Journal on Mental Retardation, 112, 450–461.

    Article  PubMed  Google Scholar 

  • Bolton, P. F., Pickles, A., Murphy, M., & Rutter, M. (1998). Autism, affective and other psychiatric disorders: Patterns of familial aggregation. Psychological Medicine, 28, 385–395.

    Article  PubMed  Google Scholar 

  • Brune, C. W., Kim, S.-J., Hanna, G. L., Courchesne, E., Lord, C., Leventhal, B. L., et al. (2008). Family-based association testing of OCD-associated SNPs of SLC1A1 in an autism sample. Autism Research, 1, 108–113.

    Article  PubMed  Google Scholar 

  • Brune, C. W., Kim, S. J., Salt, J., Leventhal, B. L., Lord, C., & Cook, E. H. Jr. (2006). 5-HTTLPR genotype-specific phenotype in children and adolescents with autism. American Journal of Psychiatry, 163, 2148–2156.

    Article  PubMed  Google Scholar 

  • Carcani-Rathwell, I., Rabe-Hasketh, S., & Santosh, P. J. (2006). Repetitive and stereotyped behaviours in pervasive developmental disorders. Journal of Child Psychology and Psychiatry, 47, 573–581.

    Article  PubMed  Google Scholar 

  • Cath, D. C., Ran, N., Smit, J. H., van Balkom, A. J. L. M., & Comijs, H. C. (2008). Symptom overlap between autism spectrum disorder, generalized anxiety disorder and obsessive-compulsive disorder in adults: A preliminary case-controlled study. Psychopahtology, 41, 101–110.

    Article  Google Scholar 

  • Cohen, J. (1988). Statistical power analysis for the behavioral sciences (2nd ed.). Mahwah, NJ: Lawrence Erlbaum.

    Google Scholar 

  • Cohen, J. (1994). The earth is round (p < .05). American Psychologist, 49, 997–1003.

    Article  Google Scholar 

  • Cohen, I. L., Liu, X., Schultz, C., White, B. N., Jenkins, E. C., Brown, W. T., et al. (2003). Association of autism severity with a monoamine oxidase a functional polymorphism. Clinical Genetics, 64, 90–197.

    Article  Google Scholar 

  • Comings, D. E. (1990). Tourette syndrome and human behavior. Duarte, CA: Hope Press.

    Google Scholar 

  • Comings, D. E., Wu, S., Chiu, C., Ring, R. H., Gade, R., Ahn, C., et al. (1996). Polygenetic inheritance of Tourette syndrome, stuttering, attention deficit hyperactivity, conduct, and oppositional defiant disorder. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 67B, 264–288.

    Google Scholar 

  • Coon, H., Dunn, D., Lainhart, J., Miller, J., Hamil, C., Battaglia, A., et al. (2005). Possible association between autism and variants in the brain-expressed tryptophan hydroxylase gene (TPH2). American Journal of Medical Genetics Part B Neuropsychiatric Genetics, 135B, 42–46.

    Article  Google Scholar 

  • Cullen, B., Samuels, J., Grados, M., Landa, R., Bienvenu, O. J., Liang, K.-Y., et al. (2008). Social and communication difficulties and obsessive-compulsive disorder. Psychopathology, 41, 194–200.

    Article  PubMed  Google Scholar 

  • Dickel, D. E., Veenstra-Vander Weele, J., Cox, N. J., Wu, X., Fischer, D. J., Van Etten-Lee, M., et al. (2006). Association testing of the positional and functional candidate gen SLOC1A1/EAAC1 in early-onset obsessive-compulsive disorder. Archives of General Psychiatry, 63, 778–785.

    Article  PubMed  Google Scholar 

  • Feise, R. J. (2002). Do multiple outcome measures require p-value adjustment? BMC Medical Research Methodology, 2.

  • Flint, J., & Mackay, T. F. C. (2009). Genetic architecture of quantitative traits in mice, flies, and humans. Genome Research, 19, 723–733.

    Article  PubMed  Google Scholar 

  • Fong, L., Wilgosh, L., & Sobsey, D. (1993). The experience of parenting an adolescent with autism. International Journal of Disability, Development, and Education, 40, 105–113.

    Article  Google Scholar 

  • Gadow, K.D., DeVincent, C.J., Olvet, D.M., & Hatchwell, E. (2009a). Association of DRD4 polymorphism with severity oppositional defiant, separation anxiety, and repetitive behaviors in children with autism spectrum disorder. Manuscript submitted for publication.

  • Gadow, K. D., DeVincent, C. J., Pomeroy, J., & Azizian, A. (2005). Comparison of DSM-IV symptoms in elementary school-aged children with PDD versus clinic and community samples. Autism, 9, 392–415.

    Article  PubMed  Google Scholar 

  • Gadow, K. D., Nolan, E. E., Sprafkin, J., & Schwartz, J. (2002). Tics and psychiatric comorbidity in children and adolescents. Developmental Medicine and Child Neurology, 44, 330–338.

    Article  PubMed  Google Scholar 

  • Gadow, K. D., Roohi, J., DeVincent, C. J., & Hatchwell, E. (2008a). Association of ADHD, tics, and anxiety with dopamine transporter (DAT1) genotype in autism spectrum disorder. Journal of Child Psychology and Psychiatry, 49, 1331–1338.

    Article  PubMed  Google Scholar 

  • Gadow, K.D., Roohi, J., DeVincent, C.J., Kirsch, S., & Hatchwell, E. (2009b). Association of COMT (Val158Met) and BDNF (Val66Met) gene polymorphisms with anxiety, ADHD and tics in children with autism spectrum disorder. Journal of Autism and Developmental Disorders, 39, 67–74.

  • Gadow, K. D., Schwartz, J., DeVincent, C., Strong, G., & Cuva, S. (2008b). Clinical utility of autism spectrum disorder scoring algorithms for the child symptom inventory. Journal of Autism and Developmental Disorders, 38, 419–427.

    Article  PubMed  Google Scholar 

  • Gadow, K. D., & Sprafkin, J. (1986). Stony Brook Child Psychiatric Checklist-3. Stony Brook: Department of Psychiatry, State University of New York.

    Google Scholar 

  • Gadow, K. D., & Sprafkin, J. (2002). Child Symptom Inventory-4 Screening and Norms Manual. Checkmate Plus: Stony Brook, NY.

    Google Scholar 

  • Gadow, K. D, Sprafkin, J. (2008). The symptom inventories: An annotated bibliography [On-line]. Stony Brook, NY: Checkmate Plus. Available: www.checkmateplus.com.

  • Grados, M. A., Mathews, C. A., & Tourette Syndrome Association International Consortium for Genetics. (2008). Latent class analysis of Gilles de la Tourette syndrome using comorbidities: Clinical and genetic implications. Biological Psychiatry, 64, 219–225.

    Article  PubMed  Google Scholar 

  • Hollingshead, A. B. (1975). Four Factor Index of Social Status. Department of Sociology, Yale University: New Haven, CT.

    Google Scholar 

  • Howlin, P., Goode, S., Hutton, J., & Rutter, M. (2004). Adult outcome for children with autism. Journal of Child Psychology and Psychiatry, 45, 212–229.

    Article  PubMed  Google Scholar 

  • Lam, K. S. L., Bodfish, J. W., & Piven, J. (2008). Evidence for three subtypes of repetitive behavior in autism that differ in familiarity and association with other symptoms. Journal of Child Psychology and Psychiatry, 49, 1193–1200.

    PubMed  Google Scholar 

  • Lecavalier, L., Gadow, K. D., DeVincent, C. J., & Edwards, M. C. (2009a). Validation of DSM-IV model of psychiatric syndromes in children with autism spectrum disorder. Journal of Autism and Developmental Disorders, 39, 278–289.

    Article  PubMed  Google Scholar 

  • Lecavalier, L., Gadow, K. D., DeVincent, C. J., Houts, C., & Edwards, M. C. (2009b). Deconstructing the PDD clinical phenotype: Internal validity of the DSM-IV. Journal of Child Psychology and Psychiatry, 50, 1246–1254.

    Article  PubMed  Google Scholar 

  • Lecavalier, L., Leone, S., & Wiltz, J. (2006). The impact of behaviour problems on caregiver stress in young people with autism spectrum disorders. Journal of Intellectual Disability Research, 50, 172–183.

    Article  PubMed  Google Scholar 

  • Lord, C., Risi, S., Lambrecht, L., Cook, E. H., Jr, Leventhal, B. L., DiLavore, P. C., et al. (2000). The autism diagnostic observation schedule-generic: A standard measure of social and communication deficits associated with the spectrum of autism. Journal of Autism and Developmental Disorders, 30, 205–223.

    Article  PubMed  Google Scholar 

  • Mandy, W. P. L., & Skuse, D. H. (2008). Research review: What is the association between the social-communication element of autism and repetitive interests, behaviours and activities? Child Psychology and Psychiatry, 49, 795–808.

    Article  Google Scholar 

  • Matson, J. L., & Dempsey, T. (2009). The nature and treatment of compulsions, obsessions, and rituals in people with developmental disabilities. Research in Developmental Disabilities, 30, 603–611.

    Article  PubMed  Google Scholar 

  • Moss, J., Oliver, C., Arron, K., Burbidge, C., & Berg, K. (2009). The prevelance and phenomenology of repetitive behavior in genetic syndromes. Journal of Autism and Developmental Disorders, 39, 572–588.

    Article  PubMed  Google Scholar 

  • Mulder, E. J., Anderson, G. M., Kema, I. P., Brugman, A. M., Ketelaars, C. E. J., de Bildt, A., et al. (2005). Serotonin transporter intron 2 polymorphism associated with rigid-compulsive behaviors in Dutch individuals with pervasive developmental disorder. American Journal of Medical Genetics Part B Neuropsychiatric Genetics, B133, 93–96.

    Article  Google Scholar 

  • Perneger, T. V. (1998). What’s wrong with Bonferroni adjustments. BMJ, 316, 1236–1238.

    PubMed  Google Scholar 

  • Piven, J., & Palmer, P. (1999). Psychiatric disorder and the broad autism phenotype: Evidence from family study of multiple-incidence autistic families. American Journal of Psychiatry, 156, 557–563.

    PubMed  Google Scholar 

  • Roohi, J., DeVincent, C. J., Hatchwell, E., & Gadow, K. D. (2009). Association of a monoamine oxidase-A gene promoter polymorphism with ADHD and anxiety in boys with autism spectrum disorder. Journal of Autism and Developmental Disorders, 39, 67–74.

    Article  PubMed  Google Scholar 

  • Rothman, K. (1990). No adjustments are needed for multiple comparisons. Epidemiology, 1, 43–46.

    Article  PubMed  Google Scholar 

  • Rowe, D. C., Stever, C., Gard, J. M. C., Cleveland, H. H., Sanders, M. L., Abramowitz, A., et al. (1998). The relation of the dopamine transporter gene (DAT1) to symptoms of internalizing disorders in children. Behavior Genetics, 28, 215–225.

    Article  PubMed  Google Scholar 

  • Rutter, M., LeCouteur, A., & Lord, C. (2003). Autism Diagnostic Interview-Revised. Western Psychological Services: Los Angeles, CA.

    Google Scholar 

  • Sacco, R., Papaleo, V., Hager, J., Rousseau, F., Moessner, R., Militerni, R., et al. (2007). Case-control and family-based association studies of candidate gene in autistic disorder and its endophenotypes: TPH2 and GLO1. BMC Medical Genetics, 8, 11.

    Article  PubMed  Google Scholar 

  • Sakurai, T., Reichert, J., Hoffman, E. J., Cai, G., Jones, H. B., Faham, M., et al. (2008). A large-scale screen for coding variants in SERT/SLC6A4 in autism spectrum disorders. Autism Research, 1, 251–257.

    Article  PubMed  Google Scholar 

  • Stewart, S. E., Fagerness, J. A., Platko, J., Smoller, J. W., Scharf, J. M., Illmann, C., et al. (2007). Association of the SLC1A1 glutamate transporter gene and obsessive-compulsive disorder. American Journal of Medical Genetics Part B Neurospychiatric Genetics, 144B, 1027–1033.

    Article  Google Scholar 

  • Sutcliffe, J. S., Delahanty, R. J., Prasad, H. C., McCauley, J. L., Han, Q., Jiang, L., et al. (2005). Allelic heterogeneity at the serotonin transporter locus (SLC6A4) confers susceptibility to autism and rigid-compulsive behaviors. American Journal of Human Genetics, 77, 265–279.

    Article  PubMed  Google Scholar 

  • Tordjman, S., Gutknecht, L., Carlier, M., Spitz, E., Antoine, C., Slama, F., et al. (2001). Role of the serotonin transporter gene in the behavioral expression of autism. Molecular Psychiatry, 6, 434–439.

    Article  PubMed  Google Scholar 

  • Wang, Y., Adamczyk, A., Shugart, Y.Y., Samuels, J.F., Grados, M.A., Greenberg, B.D., et al. (2009). A screen of SLC1A1 for OCD-related alleles. American Journal of Medical Genetics Part B. doi 10.1002/ajmg.b.31001.

  • Wendland, J. R., Moya, P. R., Timpano, K. R., Anavitarte, A. P., Kruse, M. R., Wheaton, M. G., et al. (2009). A haplotype containing quantitative trait loci for SLC 1A1 gene expression and its association with obsessive-compulsive disorder. Archives of General Psychiatry, 66, 408–416.

    Article  PubMed  Google Scholar 

  • White, S.W., Oswald, D., Ollendick, T., & Scahill, L. (2009). Anxiety in children and adolescents with autism spectrum disorders. Clinical Psychology Review, 29, 216–229.

    Google Scholar 

  • Wood, J.J., Drahota, A., Sze, K., Har, K., Chiu, A., & Langer, D.A. (2008). Cognitive behavioural therapy for anxiety in children with autism Spectrum disorders: a randomized, controlled trial. Journal of Child Psychology and Psychiatry, 50, 224–234.

    Google Scholar 

  • Zandt, F., Prior, M., & Kyrios, M. (2007). Repetitive behaviour in children with high functioning autism and obsessive compulsive disorder. Journal of Autism and Developmental Disorders, 37, 251–259.

    Article  PubMed  Google Scholar 

  • Zhang, J., Quan, H., Ng, J., & Stepanavage, M. E. (1997). Some statistical methods for multiple endpoints in clinical trials. Controlled Clinical Trials, 18, 204–221.

    Article  PubMed  Google Scholar 

  • Zhou, L., Myers, A. N., Vandersteen, J. G., Wang, L., & Wittwer, C. T. (2004). Closed-tube genotyping with unlabeled oligonucleotide probes and a saturating DNA dye. Clinical Chemistry, 50, 328–335. Epub 2004 May 27.

    Article  Google Scholar 

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Acknowledgements

This study was supported, in part, by grants from the National Institutes of Health (GCRC grant No. M01RR10710), the National Alliance for Autism Research, the Matt and Debra Cody Center for Autism and Developmental Disorders, and charitable contributions. The authors wish to thank Dr. John Pomeroy for supervising the clinical diagnoses and two anonymous reviewers for their helpful suggestions.

Financial Disclosures

Kenneth D. Gadow: shareholder in Checkmate Plus, publisher of the Child Symptom Inventory-4; Jasmin Roohi: none; Carla J. DeVincent: none; Sarah Kirsch: none; Eli Hatchwell: none.

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Authors and Affiliations

  1. Department of Psychiatry, Stony Brook University, New York, NY, USA

    Kenneth D. Gadow

  2. Department of Genetics, Stony Brook University, Stony Brook, NY, USA

    Jasmin Roohi

  3. Department of Pediatrics, Stony Brook University, Stony Brook, NY, USA

    Carla J. DeVincent

  4. Department of Pathology, Stony Brook University, Stony Brook, NY, USA

    Sarah Kirsch & Eli Hatchwell

  5. Department of Psychiatry, Stony Brook University, Putnam Hall, South Campus, Stony Brook, NY, 11794-8790, USA

    Kenneth D. Gadow

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  1. Kenneth D. Gadow
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Correspondence to Kenneth D. Gadow.

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Gadow, K.D., Roohi, J., DeVincent, C.J. et al. Brief Report: Glutamate Transporter Gene (SLC1A1) Single Nucleotide Polymorphism (rs301430) and Repetitive Behaviors and Anxiety in Children with Autism Spectrum Disorder. J Autism Dev Disord 40, 1139–1145 (2010). https://doi.org/10.1007/s10803-010-0961-7

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  • DOI: https://doi.org/10.1007/s10803-010-0961-7

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