1. ¹Department of Psychiatry, Cellular and Molecular Division, The Toronto Western Research Institute, University Health Network, Toronto, ON, Canada
2. ²Department of Psychiatry, Brain and Behaviour Programme, The Hospital for Sick Children, Toronto, ON, Canada
3. ³Division of Neurology, Department of Paediatrics, Brain and Behaviour Programme, The Hospital for Sick Children, Toronto, ON, Canada
4. ⁴The Child Development Center, The University of California, Irvine, CA
5. ⁵Neurogenetics Section, The Centre for Addiction and Mental Health, Clarke Division, University of Toronto, Toronto, ON, Canada

Correspondence: Dr CL Barr, Cell and Molecular Division, The Toronto Western Hospital, 399 Bathurst St, MP14-302, Toronto, ON, Canada M5T 1S8. E-mail: CBarr@uhnres.utoronto.ca

⁶These authors contributed equally to this work.

Received 19 November 2004; Revised 10 June 2005; Accepted 13 June 2005; Published online 9 August 2005.

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.