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Allelic variants of SNAP25 in a family-based sample of ADHD

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Summary

Altered neurotransmission has been suggested to be a crucial factor in the pathophysiology of attention-deficit/hyperactivity disorder ADHD. Subsequently genes encoding for synaptic proteins have been investigated in candidate gene studies. These proteins mediate the release of neurotransmitters into the synaptic cleft in the process of signal transduction by forming a transient complex, enabling the junction of vesicle and synaptic membrane. One of the core proteins of this complex is the synaptosomal-associated protein 25 (SNAP25). It is one of the most validated candidate genes in ADHD according to meta-analyses. However, differing results were observed in previous studies, some of which were not able to observe association with ADHD. In this study we aimed to investigate association of genetic variants of SNAP25 located in the putative promoter region of SNAP25 and a SNP in intron 8, previously reported to associated with ADHD. A family based design was applied to detect preferential transmission of genetic variants. In our German ADHD sample no preferential transmission of either variant could be observed. Further investigation considering sub-sample analysis regarding response to D-amphetamine could enlight the role of SNAP25 in ADHD.

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References

  • Apa (2000) Diagnostic and statistical manual of mental disorders, p 155

  • RA Barkley TL Shelton C Crosswait M Moorehouse K Fletcher S Barrett L Jenkins L Metevia (2002) ArticleTitlePreschool children with disruptive behavior: three-year outcome as a function of adaptive disability Dev Psychopathol 14 45–67 Occurrence Handle11893094 Occurrence Handle10.1017/S0954579402001037

    Article  PubMed  Google Scholar 

  • CL Barr Y Feng K Wigg S Bloom W Roberts M Malone R Schachar R Tannock JL Kennedy (2000) ArticleTitleIdentification of DNA variants in the SNAP-25 gene and linkage study of these polymorphisms and attention-deficit/hyperactivity disorder Mol Psychiatry 5 405–409 Occurrence Handle10889551 Occurrence Handle10.1038/sj.mp.4000733 Occurrence Handle1:CAS:528:DC%2BD3cXlslGjtLc%3D

    Article  PubMed  CAS  Google Scholar 

  • T Becker M Knapp (2004) ArticleTitleA powerful strategy to account for multiple testing in the context of haplotype analysis Am J Hum Genet 75 561–570 Occurrence Handle15290652 Occurrence Handle10.1086/424390 Occurrence Handle1:CAS:528:DC%2BD2cXnvFaktLY%3D

    Article  PubMed  CAS  Google Scholar 

  • KJ Brookes J Knight X Xu P Asherson (2005) ArticleTitleDNA pooling analysis of ADHD and genes regulating vesicle release of neurotransmitters Am J Med Genet B Neuropsychiatr Genet 139 33–37 Occurrence Handle16082702 Occurrence Handle1:STN:280:DC%2BD2MrntFSkuw%3D%3D

    PubMed  CAS  Google Scholar 

  • K Brophy Z Hawi A Kirley M Fitzgerald M Gill (2002) ArticleTitleSynaptosomal-associated protein 25 (SNAP-25) and attention deficit hyperactivity disorder (ADHD): evidence of linkage and association in the Irish population Mol Psychiatry 7 913–917 Occurrence Handle12232787 Occurrence Handle10.1038/sj.mp.4001092 Occurrence Handle1:CAS:528:DC%2BD38XntVaitLc%3D

    Article  PubMed  CAS  Google Scholar 

  • KJ Bruno CS Freet RC Twining K Egami PS Grigson EJ Hess (2007) ArticleTitleAbnormal latent inhibition and impulsivity in coloboma mice, a model of ADHD Neurobiol Dis 25 206–216 Occurrence Handle17064920 Occurrence Handle10.1016/j.nbd.2006.09.009 Occurrence Handle1:CAS:528:DC%2BD28Xht1Cls73J

    Article  PubMed  CAS  Google Scholar 

  • BJ Casey JT Nigg S Durston (2007) ArticleTitleNew potential leads in the biology and treatment of attention-deficit/hyperactivity disorder Curr Opin Neurol 20 119–224 Occurrence Handle17351480 Occurrence Handle10.1097/WCO.0b013e3280a02f78 Occurrence Handle1:STN:280:DC%2BD2s3hvFSqtw%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • YA Chen SJ Scales SM Patel YC Doung RH Scheller (1999) ArticleTitleSNARE complex formation is triggered by Ca2+ and drives membrane fusion Cell 97 165–174 Occurrence Handle10219238 Occurrence Handle10.1016/S0092-8674(00)80727-8 Occurrence Handle1:CAS:528:DyaK1MXislentrY%3D

    Article  PubMed  CAS  Google Scholar 

  • J Elia BG Borcherding JL Rapoport CS Keysor (1991) ArticleTitleMethylphenidate and dextroamphetamine treatments of hyperactivity: are there true nonresponders? Psychiatry Res 36 141–155 Occurrence Handle2017529 Occurrence Handle10.1016/0165-1781(91)90126-A Occurrence Handle1:STN:280:DyaK3M3gsVyqtw%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • SV Faraone AE Doyle (2001) ArticleTitleThe nature and heritability of attention-deficit/hyperactivity disorder Child Adolesc Psychiatry Clin N Am 10 299–316 Occurrence Handle1:STN:280:DC%2BD3M3ltlymtw%3D%3D

    CAS  Google Scholar 

  • SV Faraone SA Khan (2006) ArticleTitleCandidate gene studies of attention-deficit/ hyperactivity disorder J Clin Psychiatry 67 IssueIDSuppl 8 13–20 Occurrence Handle16961425 Occurrence Handle1:CAS:528:DC%2BD28XpsFeis74%3D

    PubMed  CAS  Google Scholar 

  • SV Faraone RH Perlis AE Doyle JW Smoller JJ Goralnick MA Holmgren P Sklar (2005) ArticleTitleMolecular genetics of attention-deficit/hyperactivity disorder Biol Psychiatry 57 1313–1323 Occurrence Handle15950004 Occurrence Handle10.1016/j.biopsych.2004.11.024 Occurrence Handle1:CAS:528:DC%2BD2MXltFSrsrg%3D

    Article  PubMed  CAS  Google Scholar 

  • Y Feng J Crosbie K Wigg T Pathare A Ickowicz R Schachar R Tannock W Roberts M Malone J Swanson JL Kennedy CL Barr (2005) ArticleTitleThe SNAP25 gene as a susceptibility gene contributing to attention-deficit hyperactivity disorder Mol Psychiatry 10 998–1005 Occurrence Handle16088329 Occurrence Handle10.1038/sj.mp.4001722 Occurrence Handle1:CAS:528:DC%2BD2MXhtFCjt7zL

    Article  PubMed  CAS  Google Scholar 

  • P Heiser S Friedel A Dempfle K Konrad J Smidt J Grabarkiewicz B Herpertz-Dahlmann H Remschmidt J Hebebrand (2004) ArticleTitleMolecular genetic aspects of attention-deficit/hyperactivity disorder Neurosci Biobehav Rev 28 625–641 Occurrence Handle15527867 Occurrence Handle10.1016/j.neubiorev.2004.09.010 Occurrence Handle1:CAS:528:DC%2BD2cXpsVOmu7g%3D

    Article  PubMed  CAS  Google Scholar 

  • EJ Hess KA Collins MC Wilson (1996) ArticleTitleMouse model of hyperkinesis implicates SNAP-25 in behavioral regulation J Neurosci 16 3104–3111 Occurrence Handle8622140 Occurrence Handle1:CAS:528:DyaK28XisFSks7c%3D

    PubMed  CAS  Google Scholar 

  • MD Jones ME Williams EJ Hess (2001) ArticleTitleAbnormal presynaptic catecholamine regulation in a hyperactive SNAP-25-deficient mouse mutant Pharmacol Biochem Behav 68 669–676 Occurrence Handle11526963 Occurrence Handle10.1016/S0091-3057(01)00481-6 Occurrence Handle1:CAS:528:DC%2BD3MXjtFGgu7c%3D

    Article  PubMed  CAS  Google Scholar 

  • S King S Griffin Z Hodges H Weatherly C Asseburg G Richardson S Golder E Taylor M Drummond R Riemsma (2006) ArticleTitleA systematic review and economic model of the effectiveness and cost-effectiveness of methylphenidate, dexamfetamine and atomoxetine for the treatment of attention deficit hyperactivity disorder in children and adolescents Health Technol Assess 10 iii–iv Occurrence Handle16796929 Occurrence Handle1:STN:280:DC%2BD28zotFeqtg%3D%3D

    PubMed  CAS  Google Scholar 

  • M Knapp T Becker (2003) ArticleTitleFamily-based association analysis with tightly linked markers Hum Hered 56 2–9 Occurrence Handle14614233 Occurrence Handle10.1159/000073727

    Article  PubMed  Google Scholar 

  • V Kustanovich B Merriman J Mcgough JT Mccracken SL Smalley SF Nelson (2003) ArticleTitleBiased paternal transmission of SNAP-25 risk alleles in attention-deficit hyperactivity disorder Mol Psychiatry 8 309–315 Occurrence Handle12660803 Occurrence Handle10.1038/sj.mp.4001247 Occurrence Handle1:CAS:528:DC%2BD3sXitlyqsLg%3D

    Article  PubMed  CAS  Google Scholar 

  • KP Lesch D Bengel A Heils SZ Sabol BD Greenberg S Petri J Benjamin CR Muller DH Hamer DL Murphy (1996) ArticleTitleAssociation of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region Science 274 1527–1531 Occurrence Handle8929413 Occurrence Handle10.1126/science.274.5292.1527 Occurrence Handle1:CAS:528:DyaK28Xnt1ansL8%3D

    Article  PubMed  CAS  Google Scholar 

  • C Mehler-Wex P Riederer M Gerlach (2006) ArticleTitleDopaminergic dysbalance in distinct basal ganglia neurocircuits: implications for the pathophysiology of Parkinson’s disease, schizophrenia and attention deficit hyperactivity disorder Neurotox Res 10 167–179 Occurrence Handle17197367 Occurrence Handle1:CAS:528:DC%2BD2sXjsFekt7w%3D Occurrence Handle10.1007/BF03033354

    Article  PubMed  CAS  Google Scholar 

  • J Mill S Richards J Knight S Curran E Taylor P Asherson (2004) ArticleTitleHaplotype analysis of SNAP-25 suggests a role in the aetiology of ADHD Mol Psychiatry 9 801–810 Occurrence Handle15007392 Occurrence Handle10.1038/sj.mp.4001482 Occurrence Handle1:CAS:528:DC%2BD2cXlvFCgs7c%3D

    Article  PubMed  CAS  Google Scholar 

  • JR O’connell DE Weeks (1998) ArticleTitlePedCheck: a program for identification of genotype incompatibilities in linkage analysis Am J Hum Genet 63 259–266 Occurrence Handle9634505 Occurrence Handle10.1086/301904 Occurrence Handle1:STN:280:DyaK1c3pvFyhsA%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • SR Pliszka (2005) ArticleTitleThe neuropsychopharmacology of attention-deficit/ hyperactivity disorder Biol Psychiatry 57 1385–1390 Occurrence Handle15950012 Occurrence Handle10.1016/j.biopsych.2004.08.026 Occurrence Handle1:CAS:528:DC%2BD2MXltFSrs78%3D

    Article  PubMed  CAS  Google Scholar 

  • VA Russell (2007) ArticleTitleNeurobiology of animal models of attention-deficit/ hyperactivity disorder J Neurosci Methods 161 185–198 Occurrence Handle17275916 Occurrence Handle10.1016/j.jneumeth.2006.12.005

    Article  PubMed  Google Scholar 

  • BG Schimmelmann S Friedel H Christiansen A Dempfle A Hinney J Hebebrand (2006) ArticleTitleGenetic findings in attention-deficit and hyperactivity disorder (ADHD) Z Kinder Jugendpsychiatr Psychother 34 425–433 Occurrence Handle17094061 Occurrence Handle10.1024/1422-4917.34.6.425

    Article  PubMed  Google Scholar 

  • TL Shelton RA Barkley C Crosswait M Moorehouse K Fletcher S Barrett L Jenkins L Metevia (2000) ArticleTitleMultimethod psychoeducational intervention for preschool children with disruptive behavior: two-year post-treatment follow-up J Abnorm Child Psychol 28 253–266 Occurrence Handle10885683 Occurrence Handle10.1023/A:1005144304071 Occurrence Handle1:STN:280:DC%2BD3M%2FhsFGqtA%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • SC Steffensen SJ Henriksen MC Wilson (1999) ArticleTitleTransgenic rescue of SNAP-25 restores dopamine-modulated synaptic transmission in the coloboma mutant Brain Res 847 186–195 Occurrence Handle10575087 Occurrence Handle10.1016/S0006-8993(99)02023-5 Occurrence Handle1:CAS:528:DyaK1MXnsVKmsrg%3D

    Article  PubMed  CAS  Google Scholar 

  • TC Sudhof (2004) ArticleTitleThe synaptic vesicle cycle Annu Rev Neurosci 27 509–547 Occurrence Handle15217342 Occurrence Handle10.1146/annurev.neuro.26.041002.131412 Occurrence Handle1:CAS:528:DC%2BD2cXmslantLs%3D

    Article  PubMed  CAS  Google Scholar 

  • LC Tafoya M Mameli T Miyashita JF Guzowski CF Valenzuela MC Wilson (2006) ArticleTitleExpression and function of SNAP-25 as a universal SNARE component in GABAergic neurons J Neurosci 26 7826–7838 Occurrence Handle16870728 Occurrence Handle10.1523/JNEUROSCI.1866-06.2006 Occurrence Handle1:CAS:528:DC%2BD28XnvF2isbg%3D

    Article  PubMed  CAS  Google Scholar 

  • JE Wigginton GR Abecasis (2005) ArticleTitlePEDSTATS: descriptive statistics, graphics and quality assessment for gene mapping data Bioinformatics 21 3445–3447 Occurrence Handle15947021 Occurrence Handle10.1093/bioinformatics/bti529 Occurrence Handle1:CAS:528:DC%2BD2MXovVKru70%3D

    Article  PubMed  CAS  Google Scholar 

  • MC Wilson (2000) ArticleTitleColoboma mouse mutant as an animal model of hyperkinesis and attention deficit hyperactivity disorder Neurosci Biobehav Rev 24 51–57 Occurrence Handle10654661 Occurrence Handle10.1016/S0149-7634(99)00064-0 Occurrence Handle1:CAS:528:DC%2BD3cXjtVylsA%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • H Zhao S Zhang KR Merikangas M Trixler DB Wildenauer F Sun KK Kidd (2000) ArticleTitleTransmission/disequilibrium tests using multiple tightly linked markers Am J Hum Genet 67 936–946 Occurrence Handle10968775 Occurrence Handle10.1086/303073 Occurrence Handle1:CAS:528:DC%2BD3cXnsVCgsLw%3D

    Article  PubMed  CAS  Google Scholar 

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Correspondence to T. J. Renner.

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Correspondence: Tobias J. Renner, Department of Child and Adolescent Psychiatry and Psychotherapy, University of Würzburg, Füchsleinstr. 15, 97080 Würzburg, Germany

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Renner, T., Walitza, S., Dempfle, A. et al. Allelic variants of SNAP25 in a family-based sample of ADHD. J Neural Transm 115, 317–321 (2008). https://doi.org/10.1007/s00702-007-0840-3

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  • DOI: https://doi.org/10.1007/s00702-007-0840-3

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