Abstract
The synaptosomal-associated protein of 25 kDa gene (SNAP25) has been suggested as a genetic susceptibility factor in attention-deficit hyperactivity disorder (ADHD) based on the mouse strain coloboma. This strain is hemizygous for the SNAP25 gene and displays hyperactivity that responds to dextroamphetamine, but not to methylphenidate. Previously, we reported association of SNAP25 and ADHD using two polymorphisms. To further investigate this gene, we screened the exons for DNA variation and genotyped ten additional polymorphisms in an expanded sample of families from Toronto and a second sample of families collected in Irvine, CA. Significant results were observed in the Toronto sample for four markers, although not in the Irvine sample. The paper discusses the possible influence of the selection criteria on these differential results. The Irvine sample selected subjects that met the DSM-IV combined subtype diagnosis, whereas the Toronto sample included all subtypes. Analysis of the DSM-IV subtypes in the Toronto sample indicated that the differential results were not attributable to ADHD subtype. Differences in ethnicity, differential medication response, and other clinical characteristics of the samples cannot be ruled out at this time. Quantitative analysis of the dimensions of hyperactivity/impulsivity and inattention in the Toronto sample found that both behavioral traits were associated with SNAP25. Our findings continue to support SNAP25 in the susceptibility to ADHD.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Bajjalieh SM, Scheller RH . The biochemistry of neurotransmitter secretion. J Biol Chem 1995; 270: 1971–1974.
Osen-Sand A, Catsicas M, Staple JK, Jones KA, Ayala G, Knowles J et al. Inhibition of axonal growth by SNAP-25 antisense oligonucleotides in vitro and in vivo. Nature 1993; 364: 445–448.
Hess EJ, Jinnah HA, Kozak CA, Wilson MC . Spontaneous locomotor hyperactivity in a mouse mutant with a deletion including the Snap gene on chromosome 2. J Neurosci 1992; 12: 2865–2874.
Raber J, Mehta PP, Kreifeldt M, Parsons LH, Weiss F, Bloom FE et al. Coloboma hyperactive mutant mice exhibit regional and transmitter-specific deficits in neurotransmission. J Neurochem 1997; 68: 176–186.
Jones MD, Williams ME, Hess EJ . Abnormal presynaptic catecholamine regulation in a hyperactive SNAP-25-deficient mouse mutant. Pharmacol Biochem Behav 2001; 68: 669–676.
Hess EJ, Collins KA, Wilson MC . Mouse model of hyperkinesis implicates SNAP-25 in behavioral regulation. J Neurosci 1996; 16: 3104–3111.
Washbourne P, Thompson PM, Carta M, Costa ET, Mathews JR, Lopez-Bendito G et al. Genetic ablation of the t-SNARE SNAP-25 distinguishes mechanisms of neuroexocytosis. Nat Neurosci 2002; 5: 19–26.
Barr CL, Feng Y, Wigg K, Bloom S, Roberts W, Malone M et al. Identification of DNA variants in the SNAP-25 gene and linkage study of these polymorphisms and attention-deficit hyperactivity disorder. Mol Psychiatry 2000; 5: 405–409.
Mill J, Curran S, Kent L, Gould A, Huckett L, Richards S et al. Association study of a SNAP-25 microsatellite and attention deficit hyperactivity disorder. Am J Med Genet 2002; 114: 269–271.
Brophy K, Hawi Z, Kirley A, Fitzgerald M, Gill M . Synaptosomal-associated protein 25 (SNAP-25) and attention deficit hyperactivity disorder (ADHD): evidence of linkage and association in the Irish population. Mol Psychiatry 2002; 7: 913–917.
Kustanovich V, Merriman B, McGough J, McCracken JT, Smalley SL, Nelson SF . Biased paternal transmission of SNAP-25 risk alleles in attention-deficit hyperactivity disorder. Mol Psychiatry 2003; 8: 309–315.
Mill J, Richards S, Knight J, Curran S, Taylor E, Asherson P . Haplotype analysis of SNAP-25 suggests a role in the aetiology of ADHD. Mol Psychiatry 2004; 9: 801–810.
Barr CL, Wigg K, Malone M, Schachar R, Tannock R, Roberts W et al. Linkage study of catechol-O-methyltransferase and attention-deficit hyperactivity disorder. Am J Med Genet 1999; 88: 710–713.
Barr CL, Feng Y, Wigg KG, Schachar R, Tannock R, Roberts W et al. 5′ untranslated region of the dopamine D4 receptor gene and attention-deficit hyperactivity disorder. Am J Med Genet (Neuropsychiatr Genet) 2001; 105: 84–90.
Sunohara GA, Roberts W, Malone M, Schachar RJ, Tannock R, Basile VS et al. Linkage of the dopamine D4 receptor gene and attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry 2000; 39: 1537–1542.
Quist JF, Barr CL, Schachar R, Roberts W, Malone M, Tannock R et al. Evidence for the serotonin HTR2A receptor gene as a susceptibility factor in attention deficit hyperactivity disorder (ADHD). Mol Psychiatry 2000; 5: 537–541.
LaHoste GJ, Swanson JM, Wigal SB, Glabe C, Wigal T, King N et al. Dopamine D4 receptor gene polymorphism is associated with attention deficit hyperactivity disorder. Mol Psychiatry 1996; 1: 121–124.
Swanson JM, Sunohara GA, Kennedy JL, Regino R, Fineberg E, Wigal T et al. Association of the dopamine receptor D4 (DRD4) gene with a refined phenotype of attention deficit hyperactivity disorder (ADHD): a family-based approach. Mol Psychiatry 1998; 3: 38–41.
Shaffer D, Fisher P, Dulcan MK, Davies M, Piacentini J, Schwab-Stone ME et al. The NIMH Diagnostic Interview Schedule for Children Version 2.3 (DISC- 2.3): description, acceptability, prevalence rates, and performance in the MECA Study. Methods for the Epidemiology of Child and Adolescent Mental Disorders Study. J Am Acad Child Adolesc Psychiatry 1996; 35: 865–877.
Orita M, Iwahana H, Kanazawa H, Hayashi K, Sekiya T . Detection of polymorphisms of human DNA by gel electrophoresis as single-strand conformation polymorphisms. Proc Natl Acad Sci USA 1989; 86: 2766–2770.
Sham PC, Curtis D . An extended transmission/disequilibrium test (TDT) for multi-allele marker loci. Ann Hum Genet 1995; 59 (Part 3): 323–336.
Clayton D . A generalization of the transmission/disequilibrium test for uncertain-haplotype transmission. Am J Hum Genet 1999; 65: 1170–1177.
Horvath S, Xu X, Laird NM . The family based association test method: strategies for studying general genotype—phenotype associations. Eur J Hum Genet 2001; 9: 301–306.
Martin N, Scourfield J, McGuffin P . Observer effects and heritability of childhood attention-deficit hyperactivity disorder symptoms. Br J Psychiatry 2002; 180: 260–265.
American Psychiatric Association. American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 4th ed. American Psychiatric Association: Washington DC, 1994.
Davids E, Zhang K, Tarazi FI, Baldessarini RJ . Animal models of attention-deficit hyperactivity disorder. Brain Res Brain Res Rev 2003; 42: 1–21.
Heyser CJ, Wilson MC, Gold LH . Coloboma hyperactive mutant exhibits delayed neurobehavioral developmental milestones. Brain Res Dev Brain Res 1995; 89: 264–269.
Acknowledgements
This work was supported by grants from The Hospital for Sick Children Psychiatric Endowment Fund (CLB), the Canadian Institutes of Health Research MT14336 and MOP-14336 (CLB), NIMH U01:MH50440 (JS), NICHD MRC Grant HD99-004 (JS), and the Irvine Health Foundation (JS).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Feng, Y., Crosbie, J., Wigg, K. et al. The SNAP25 gene as a susceptibility gene contributing to attention-deficit hyperactivity disorder. Mol Psychiatry 10, 998–1005 (2005). https://doi.org/10.1038/sj.mp.4001722
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.mp.4001722
Keywords
This article is cited by
-
Vesicle trafficking with snares: a perspective for autism
Molecular Biology Reports (2022)
-
Neonatal Rotenone Administration Induces Psychiatric Disorder-Like Behavior and Changes in Mitochondrial Biogenesis and Synaptic Proteins in Adulthood
Molecular Neurobiology (2021)
-
STX1A gene variations contribute to the susceptibility of children attention-deficit/hyperactivity disorder: a case–control association study
European Archives of Psychiatry and Clinical Neuroscience (2019)
-
The Association of SNAP25 Gene Polymorphisms in Attention Deficit/Hyperactivity Disorder: a Systematic Review and Meta-Analysis
Molecular Neurobiology (2017)
-
Synaptosome-Associated Protein 25 (SNAP25) Gene Association Analysis Revealed Risk Variants for ASD, in Iranian Population
Journal of Molecular Neuroscience (2017)