Skip to main content
Search
Search
    Quick Search anywhere
    Quick search in Citations
Advanced Search
Skip main navigationClose Drawer MenuOpen Drawer Menu
Previous article
Next article
Übersichtsarbeit

Genetische Befunde bei der Aufmerksamkeitsdefizit- und Hyperaktivitätsstörung (ADHS)

Published Online:November 10, 2006https://doi.org/10.1024/1422-4917.34.6.425

Abstract

Zusammenfassung: Die Aufmerksamkeitsdefizit- und Hyperaktivitätsstörung (ADHS) ist mit einer Prävalenz von 3-7% eine häufige kinder- und jugendpsychiatrische Störung. Auf der Basis formalgenetischer Studien ergibt sich eine Heritabilitätsschätzung von 60-80% für ADHS mit einem ca. 5-fach erhöhten Risiko für erstgradige Verwandte von Betroffenen. Bislang vier Genomscans lieferten potentiell relevante chromosomale Regionen, insbesondere den einheitlichen Kopplungsbefund auf 5p13. Aus einer Vielzahl von Assoziationsstudien zu Kandidatengenen deuten aktuelle Metaanalysen auf die Relevanz der Gene der dopaminergen Rezeptoren DRD4 und DRD5 sowie des serotonergen Rezeptors HTR1B und des Synaptosomal Assoziierten Proteins (SNAP-25). In Tiermodellen liegen vorwiegend Paradigmen für Hyperaktivität vor; diese sind in knockout- und Quantitative Trait Loci (QTL) Designs mit viel versprechenden Ergebnissen zum dopaminergen System untersucht worden. Es ist davon auszugehen, dass erst das Zusammenwirken verschiedener Gen-Varianten mit jeweils moderatem bis hin zu kleinem Effekt den Phänotyp ADHS bedingen (Oligo-/ Polygenie) und bei verschiedenen Betroffenen unterschiedliche Kombinationen von prädisponierenden Gen-Polymorphismen zu ADHS führen können. Entsprechend sind für molekulargenetische Studien große Fallzahlen notwendig und die bisherigen Befunde als vorläufig zu interpretieren. Zukunftsweisend für die molekulargenetische Aufklärung von ADHS sind SNP-basierte Genomscans, mit denen 10 000-1 000 000 einzelne Polymorphismen (SNPs) gleichzeitig untersucht werden können. Tiermodelle liefern Hinweise auf die Funktion relevanter Kandidatengene und tragen zur Erweiterung der bislang teilweise widersprüchlichen Kenntnisse zur Neurobiologie des ADHS bei.


Genetic findings in Attention-Deficit and Hyperactivity Disorder (ADHD)

Summary: Attention-Deficit and Hyperactivity Disorder (ADHD) is a common child and adolescent psychiatric disorder with a prevalence rate of 3-7%. Formal genetic studies provided an estimated heritability of 0.6-0.8 and an approximately five-fold elevated risk for ADHD in first-degree relatives. Currently, four genome scans have led to the identification of chromosomal regions potentially relevant in ADHD; especially the evidence for linkage to chromosome 5p13 is convincing. Meta-analyses of a large number of candidate gene studies suggest association with gene variants of the dopaminergic receptors DRD4 and DRD5, the serotonergic receptor HTR1B, and the synaptosomal receptor protein (SNAP-25). Hyperactivity has been investigated particularly in animal models, focusing on knockout- and quantitative trait loci (QTL) designs, with promising results for the dopaminergic system. It is likely that several gene polymorphisms with moderate to small effect sizes contribute to the phenotype ADHD; different combinations of such predisposing variants presumably underlie ADHD in different individuals. Therefore, large samples for molecular genetic studies are mandatory to detect these polymorphisms. Accordingly, several of today’s findings have to be regarded as preliminary. The understanding of ADHD’s neurobiology may be advanced by new technologies, such as SNP-based genome scans performed with gene chips comprising 10,000-1,000,000 SNPs, as well as using more sophisticated animal model designs.

Literatur

  • Accili, D. , Fishburn, C. S. , Drago, J. , Steiner, H. , Lachowicz, J.E. , Park, B. H. , Gauda, E. B , Lee, E. J. , Cool, M. H. , Sibley, D.R. , Gerfen, C. R. , Westphal, H. , Fuchs, S. (1996). A targeted mutation of the D3 dopamine receptor gene is associated with hyperactivity in mice. Proceedings of the National Academy of Science USA, 93, 1945– 1949 First citation in articleGoogle Scholar

  • American Psychiatric Association, (1994). Diagnostic Criteria from DSM-IV. Washington, DC: American Psychiatric Press First citation in articleGoogle Scholar

  • Anguelova, M. , Benkelfat, C. , Turecki, G. (2003). A systematic review of association studies investigating genes coding for serotonin receptors and the serotonin transporter: I. Affective disorders.. Molecular Psychiatry, 8, (6) 574– 59 First citation in articleCrossref, Google Scholar

  • Arcos-Burgos, M. , Castellanos, F. X. , Pineda, D. , Lopera, F. , Palacio, J. D. , Palacio, L. G. , Rapoport, J. L. , Berg, K. , Bailey-Wilson, J. E. , Muenke, M. (2004). Attention-deficit/hyperactivity disorder in a population isolate: linkage to loci at 4q13.2, 5q33.3, 11q22, and 17p11. American Journal of Human Genetics, 75, 998– 1014 First citation in articleCrossref Medline, Google Scholar

  • Baik, J. H. , Picetti, R. , Saiardi, A. , Thiriet, G. , Dierich, A. , Depaulis, A. , Le Meur, M. , Borrelli, E. (1995). Parkinsonian-like locomotor impairment in mice lacking dopamine D2 receptors. Nature, 377, 424– 428 First citation in articleCrossref Medline, Google Scholar

  • Bakker, S. C. , Meulen, E. M. , Buitelaar, J. K. , Sandkuijl, L. A. , Pauls, D. L. , Monsuur, A. J. , van’t Slot, R. , Minderaa, R. B. , Gunning, W. B. , Pearson, P. L. , Sinke, R. J. (2003). A Whole-Genome Scan in 164 Dutch Sib Pairs with Attention-Deficit/Hyperactivity Disorder: Suggestive Evidence for Linkage on Chromosomes 7p and 15q. American Journal of Human Genetics, 72, 1251– 1260 First citation in articleCrossref Medline, Google Scholar

  • Bhaduri, N. , Mukhopadhyay, K. (2006). Lack of significant association between -1021C—>T polymorphism in the dopamine beta hydroxylase gene and attention deficit hyperactivity disorder. Neuroscience Letter, 402, (1-2) 12– 16 First citation in articleCrossref, Google Scholar

  • Biederman, J. , Faraone, S. V. , Keenan, K. , Benjamin, J. , Krifcher, B. , Moore, C. , Sprich-Buckminster, S. , Ugaglia, K. , Jellinek, M. S. , Steingard, R. (1992). Further evidence for family-genetic risk factors in attention deficit hyperactivity disorder. Patterns of comorbidity in probands and relatives psychiatrically and pediatrically referred samples. Archives of General Psychiatry, 49, 728– 738 First citation in articleCrossref Medline, Google Scholar

  • Cheuk, D. K. , Wong, V. (2006). Meta-analysis of Association Between a Catechol-O-Methyltransferase Gene Polymorphism and Attention Deficit Hyperactivity Disorder. Behavioral Genetics, (Epub ahead of print) First citation in articleCrossref, Google Scholar

  • Curran, S. , Purcell, S. , Craig, I. , Asherson, P. , Sham, P. (2005). The serotonin transporter gene as a QTL for ADHD. American Journal of Medical Genetics, Part B, Neuropsychiatric Genetics, 134b, 42– 47 First citation in articleCrossref Medline, Google Scholar

  • Domschke, K. , Sheehan, K. , Lowe, N. , Kirley, A. , Mullins, C. , O’Sullivan, R. , Freitag, C. , Becker, T. , Conroy, J. , Fitzgerald, M. , Gill, M. , Hawi, Z. (2005). Association analysis of the monoamine oxidase A and B genes with attention deficit hyperactivity disorder (ADHD) in an Irish sample: preferential transmission of the MAO-A 941G allele to affected children. American Journal of Medical Genetics, Part B, Neuropsychiatric Genetics, 134, (1) 110– 114 First citation in articleCrossref, Google Scholar

  • Ewens, W. J. , Spielman, R. S (1995). The transmission/disequilibrium test: history, subdivision, and admixture. American Journal of Human Genetics, 57, (2) 455– 464 First citation in articleGoogle Scholar

  • Falzone, T. L. , Gelman, D. M. , Young, J. I. , Grandy, D. K. , Low, M. J. , Rubinstein, M. (2002). Absence of dopamine D4 receptors results in enhanced reactivity to unconditioned, but not conditioned, fear. European Journal of Neuroscience, 15, 158– 164 First citation in articleCrossref Medline, Google Scholar

  • Faraone, S. V. , Biederman, J. , Friedman, D. (2000). Validity of DSM-IV subtypes of attention-deficit/hyperactivity disorder: a family study perspective. Journal of the American Academy of Child and Adolescent Psychiatry, 39, (3) 300– 307 First citation in articleCrossref, Google Scholar

  • Faraone, S. V. , Doyle, A. E. (2001). The nature and heritability of attentiondeficit/hyperactivity disorder. Child and Adolescent Psychiatric Clinics of North Americaca, 10, (2) 299– 316 First citation in articleGoogle Scholar

  • Faraone, S. V. , Perlis, R. H. , Doyle, A. E. , Smoller, J. W. , Goralnick, J. J. , Holmgren, M. A. , Sklar, P. (2005). Molecular genetics of attention-deficit/hyperactivity disorder. Biological Psychiatry, 57, (11) 1313– 1323 First citation in articleCrossref, Google Scholar

  • Fisher, S. E. , Francks, C. , McCracken, J. T. , McGough, J. J. , Marlow, A. J. , MacPhie, I. L. , Newbury, D. F. , Crawford, L. R. , Palmer, C. G. , Woodward, J. A. , Del’Homme, M. , Cantwell, D. P. , Nelson, S. F. , Monaco, A. P. , Smalley, S. L. (2002). A genome-wide scan for loci involved in attention-deficit/hyperactivity disorder. American Journal of Human Genetics, 70, 1183– 1196 First citation in articleCrossref Medline, Google Scholar

  • Friedel, S. , Horro, F. F. , Wermter, A. K. , Geller, F. , Dempfle, A. , Reichwald, K. , Smidt, J. , Bronner, G. , Konrad, K. , Herpertz-Dahlmann, B. , Warnke, A. , Hemminger, U. , Linder, M. , Kiefl, H. , Goldschmidt, H. P. , Siegfried, W. , Remschmidt, H. , Hinney, A. , Hebebrand, J. (2005). Mutation screen of the brain derived neurotrophic factor gene (BDNF): identification of several genetic variants and association studies in patients with obesity, eating disorders, and attention-deficit/hyperactivity disorder. American Journal of Medical Genetics, Part B, Neuropsychiatric Genetics, 132, (1) 96– 99 First citation in articleCrossref, Google Scholar

  • Giros, B. , Jaber, M. , Jones, S. R. , Wightman, R. M. , Caron, M.G. (1996). Hyperlocomotion and indifference to cocaine and amphetamine in mice lacking the dopamine transporter. Nature, 379, 606– 612 First citation in articleCrossref Medline, Google Scholar

  • Gogos, J. A. , Morgan, M. , Luine, V. , Santha, M. , Ogawa, S. , Pfaff, D. , Karayiorgou, M. (1998). Catechol-O-methyltransferase-deficient mice exhibit sexually dimorphic changes in catecholamine levels and behavior. Proceedings of the National Academy of Science USA, 95, 9991– 9996 First citation in articleGoogle Scholar

  • Goodman, R. , Stevenson, J. (1989). A twin study of hyperactivity-II. The aetiological role of genes, family relationships and perinatal adversity. Journal of Child Psychology and Psychiatry, 30, (5) 691– 709 First citation in articleCrossref, Google Scholar

  • Hawi, Z. , Foley, D. , Kirley, A. , McCarron, M. , Fitzgerald, M. , Gill, M. (2001). Dopa decarboxylase gene polymorphisms and attention deficit hyperactivity disorder (ADHD): no evidence for association in the Irish population. Molecular Psychiatry, 6, (4) 420– 424 First citation in articleCrossref, Google Scholar

  • Hawi, Z. , Segurado, R. , Conroy, J. , Sheehan, K. , Lowe, N. , Kirley, A. , Shields, D. , Fitzgerald, M. , Gallagher, L. , Gill, M. (2005). Preferential transmission of paternal alleles at risk genes in attention-deficit/hyperactivity disorder. American Journal of Human Genetics, 77, (6) 958– 965 First citation in articleCrossref, Google Scholar

  • Hebebrand, J. , Dempfle, A. , Saar, K. , Thiele, H. , Herpertz-Dahlmann, B. , Linder, M. , Kiefl, H. , Remschmidt, H. , Hemminger, U. , Warnke, A. , Knolker, U. , Heiser, P. , Friedel, S. , Hinney, A. , Schafer, H. , Nurnberg, P. , Konrad, K. (2006). A genome-wide scan for attention-deficit/hyperactivity disorder in 155 German sib-pairs. Molecular Psychiatry, 11, (2) 196– 205 First citation in articleCrossref, Google Scholar

  • Heiser, P. , Friedel, S. , Dempfle, A. , Konrad, K. , Smidt, J. , Grabarkiewicz, J. , Herpertz-Dahlmann, B. , Remschmidt, H. , Hebebrand, J. (2004). Molecular genetic aspects of attention-deficit/hyperactivity disorder. Neuroscience Biobehavioral Reviews, 28, (6 625– 641 First citation in articleCrossref, Google Scholar

  • Holmes, A. , Hollon, T. R. , Gleason, T. C. , Liu, Z. , Dreiling, J. , Sibley, D. R. , Crawley, J. N (2001). Behavioral characterization of dopamine D5 receptor null mutant mice. Behavioral Neuroscience, 115, 1129– 1144 First citation in articleCrossref Medline, Google Scholar

  • Huotari, M. , Santha, M. , Lucas, L. R. , Karayiorgou, M. , Gogos, J. A. , Mannisto, P. T. (2002). Effect of Dopamine Uptake Inhibition on Brain Catecholamine Levels and Locomotion in Catechol-O-methyltransferase-Disrupted Mice. Journal of Pharmacology and Experimental Therapeutics, 303, 1309– 1316 First citation in articleCrossref Medline, Google Scholar

  • Kent, L. , Doerry, U. , Hardy, E. , Parmar, R. , Gingell, K. , Hawi, Z. , Kirley, A. , Lowe, N. , Fitzgerald, M. , Gill, M. , Craddock, N. (2002). Evidence that variation at the serotonin transporter gene influences susceptibility to attention deficit hyperactivity disorder (ADHD): analysis and pooled analysis. Molecular Psychiatry, 7, 908– 912 First citation in articleCrossref Medline, Google Scholar

  • Kent, L. , Green, E. , Hawi, Z. , Kirley, A. , Dudbridge, F. , Lowe, N. , Raybould, R. , Langley, K. , Bray, N. , Fitzgerald, M. , Owen, M.J. , O’Donovan, M.C. , Gil, l M. , Thapar, A. , Craddock, N. (2005). Association of the paternally transmitted copy of common Valine allele of the Val66Met polymorphism of the brain-derived neurotrophic factor (BDNF) gene with susceptibility to ADHD. Molecular Psychiatry, 10, (10) 939– 943 First citation in articleCrossref, Google Scholar

  • Laird, N. M. , Lange, C. (2006). Family-based designs in the age of large-scale gene-association studies. Nature Reviews. Genetics, 7, (5– 385 394 First citation in articleGoogle Scholar

  • Lalonde, J. , Turgay, A. , Hudson, J. I. (1998). Attention-deficit hyperactivity disorder subtypes and comorbid disruptive behaviour disorders in a child and adolescent mental health clinic. Canadian Journal of Psychiatry, 43, (6 623– 628 First citation in articleGoogle Scholar

  • Lander, E. , Kruglyak, L. (1995). Genetic dissection of complex traits: guidelines for interpreting and reporting linkage results. Nature Genetics, 1, 241– 247 First citation in articleCrossref, Google Scholar

  • Langley, K. , Payton, A. , Hamshere, M. L. , Pay, H. M. , Lawson, D. C. , Turic, D. , Ollier, W. , Worthington, J. , Owen, M. J. , O’Donovan, M. C. , Thapar, A. (2003). No evidence of association of two 5HT transporter gene polymorphisms and attention deficit hyperactivity disorder. Psychiatric Genetics, 13, 107– 110 First citation in articleMedline, Google Scholar

  • Levy, F. , Hay, D. A. , Bennett, K. S. , McStephen, M. (2005). Gender differences in ADHD subtype comorbidity. Journal of the American Academy of Child and Adolescent Psychiatry, 44, (4) 368– 376 First citation in articleCrossref, Google Scholar

  • Li, D. , Sham, P. C. , Owen, M. J. , He, L. (2006a). Metaanalysis shows significant association between dopamine system genes and attention deficit hyperactivity disorder (ADHD). Human Molecular Genetics, 15, (14) 2276– 2284 First citation in articleGoogle Scholar

  • Li, J. , Kang, C. , Wang, Y. , Zhou, R. , Wang, B. , Guan, L. , Yang, L. , Faraone, S. V. (2006b). Contribution of 5-HT2A receptor gene -1438A>G polymorphism to outcome of attention-deficit/hyperactivity disorder in adolescents. American Journal of Medical Genetics, Part B, Neuropsychiatric Genetics, 141, (5)– 473– 476 First citation in articleGoogle Scholar

  • Li, J. , Wang, Y. , Zhou, R. , Zhang, H. , Yang, L. , Wang, B. , Faraone, S. V. (2006c). Association between tryptophan hydroxylase gene polymorphisms and attention deficit hyperactivity disorder in Chinese Han population. American Journal of Medical Genetics, Part B, Neuropsychiatric Genetics, 141, (2) 126– 129 First citation in articleCrossref, Google Scholar

  • Madras, B. K. , Miller, G. M. , Fischman, A. J. (2005). The dopamine transporter and attention-deficit/hyperactivity disorder. Biological Psychiatry, 57, (11) 1397– 1409 First citation in articleCrossref, Google Scholar

  • Manor, I. , Eisenberg, J. , Tyano, S. , Sever, Y. , Cohen, H. , Ebstein, R. P. , Kotler, M. (2001). Family-based association study of the serotonin transporter promoter region polymorphism (5-HTTLPR) in attention deficit hyperactivity disorder. American Journal of Medical Genetics, Part B, Neuropsychiatric Genetics, 105, 91– 95 First citation in articleCrossref, Google Scholar

  • Martin, N. , Scourfield, J. , McGuffin, P (2002). Observer effects and heritability of childhood attention-deficit hyperactivity disorder symptoms. British Journal of Psychiatry, 180, 260– 265 First citation in articleCrossref Medline, Google Scholar

  • Moisan, M. P. , Courvoisier, H. , Bihoreau, M. T. , Gauguier, D. , Hendley, E. D. , Lathrop, M. , James, M. R. , Mormede, P. (1996). A major quantitative trait locus influences hyperactivity in the WKHA rat. Nature Genetics, 14, 471– 473 First citation in articleCrossref Medline, Google Scholar

  • Morton, N. E. (1998). Significance levels in complex inheritance. American Journal of Human Genetics, 62, 690– 697 First citation in articleCrossref Medline, Google Scholar

  • Nelson, R. J. , Young, K. A. (1998). Behavior in mice with targeted disruption of single genes. Neuroscience Biobehavior Reviews, 22, 453– 462 First citation in articleCrossref Medline, Google Scholar

  • Neuman, R. J. , Sitdhiraksa, N. , Reich, W. , Ji, T. H. , Joyner, C. A. , Sun, L. W. , Todd, R. D. (2005). Estimation of prevalence of DSM-IV and latent class-defined ADHD subtypes in a population-based sample of child and adolescent twins. Twin Research Human Genetics, 8, (4) 392– 401 First citation in articleCrossref, Google Scholar

  • Ogdie, M. N. , Fisher, S. E. , Yang, M. , Ishii, J. , Francks, C. , Loo, S. K. , Cantor, R. M. , McCracken, J. T. , McGough, J. J. , Smalley, S. L. , Nelson, S. F. (2004). Attention deficit hyperactivity disorder: fine mapping supports linkage to 5p13, 6q12, 16p13, and 17p11. American Journal of Human Genetics, 75, (4) 661– 668 First citation in articleCrossref, Google Scholar

  • Ogdie, M. N. , Macphie, I. L. , Minassian, S. L. , Yang, M. , Fisher, S. E. , Francks, C. , Cantor, R. M. , McCracken, J. T. , McGough, J. J. , Nelson, S. F. , Monaco, A. P. , Smalley, S. L. (2003). A genomewide scan for attention-deficit/hyperactivity disorder in an extended sample: suggestive linkage on 17p11. American Journal of Human Genetics, 72, (5) 1268– 1279 First citation in articleCrossref, Google Scholar

  • Ogdie, M. N. , Bakker, S. C. , Fisher, S. E. , Francks, C. , Yang, M.H. , Cantor, R. M. , Loo, S. K. , van der Meulen, E. , Pearson, P. , Buitelaar, J. , Monaco, A. , Nelson, S. F. , Sinke, R. J. , Smalley, S. L. (2006). Pooled genome-wide linkage data on 424 ADHD ASPs suggests genetic heterogeneity and a common risk locus at 5p13. Molecular Psychiatry, 11, (1) 5– 8 First citation in articleCrossref, Google Scholar

  • Pogorelov, V. M. , Rodriguiz, R. M. , Insco, M. L. , Caron, M. G. , Wetsel, W. C. (2005). Novelty seeking and stereotypic activation of behavior in mice with disruption of the Dat1 gene. Neuropsychopharmacology, 30, (10) 1818– 1831 First citation in articleGoogle Scholar

  • Rubinstein, M. , Phillips, T. J. , Bunzow, J. R. , Falzone, T. L. , Dziewczapolski, G. , Zhang, G. , Fang, Y. , Larson, J. L. , McDougall, J. A. , Chester, J. A. , Saez, C. , Pugsley, T. A. , Gershanik, O. , Low, M. J. , Grandy, D. K. (1997). Mice lacking dopamine D4 receptors are supersensitive to ethanol, cocaine, and methamphetamine. Cell, 90, 991– 1001 First citation in articleCrossref Medline, Google Scholar

  • Saudou, F. , Amara, D. A. , Dierich, A. , LeMeur, M. , Ramboz, S. , Segu, L. , Buhot, M. C. , Hen, R. (1994). Enhanced aggressive behavior in mice lacking 5-HT1B receptor. Science, 265, 1875– 1878 First citation in articleGoogle Scholar

  • Schmitz, M. , Denardin, D. , Silva, T. L. , Pianca, T. , Roman, T. , Hutz, M. H. , Faraone, S. V. , Rohde, L. A. (2006). Association Between Alpha-2a-adrenergic Receptor Gene and ADHD Inattentive Type. Biological Psychiatry, Jun 23 (Epub ahead of print) First citation in articleCrossref, Google Scholar

  • Seeger, G. , Schloss, P. , Schmidt, M. H. (2001). Functional polymorphism within the promotor of the serotonin transporter gene is associated with severe hyperkinetic disorders. Molecular Psychiatry, 6, 235– 238 First citation in articleCrossref Medline, Google Scholar

  • Smalley, S. L. , McGough, J. J. , Del’Homme, M. , NewDelman, J. , Gordon, E. , Kim, T. , Liu, A. , McCracken, J. T. (2000). Familial clustering of symptoms and disruptive behaviors in multiplex families with attention-deficit/hyperactivity disorder. Journal of the American Academy of Child and Adolescent Psychiatry, 39, (9) 1135– 1143 First citation in articleCrossref, Google Scholar

  • Smidt, J. , Heiser, P. , Dempfle, A. , Konrad, K. , Hemminger, U. , Kathofer, A. , Halbach, A. , Strub, J. , Grabarkiewicz, J. , Kiefl, H. , Linder, M. , Knolker, U. , Warnke, A. , Remschmidt, H. , Herpertz-Dahlmann, B. , Hebebrand, J. (2003). Formalgenetische Befunde zur Aufmerksamkeitsdefizit-/Hyperaktivitätsstörung. Fortschritte der Neurologie und Psychiatrie, 71, (7) 366– 377 First citation in articleGoogle Scholar

  • Sotnikova, T. D. , Beaulieu, J. M. , Gainetdinov, R. R. , Caron, M.G. (2006). Molecular biology, pharmacology and functional role of the plasma membrane dopamine transporter. CNS Neurological Disordisorders Drug Targets, 5, (1) 45– 56 First citation in articleGoogle Scholar

  • Spielewoy, C. , Roubert, C. , Hamon, M. , Nosten-Bertrand, M. , Betancur, C. , Giros, B. (2000). Behavioural disturbances associated with hyperdopaminergia in dopamine-transporter knockout mice. Behavioral Pharmacology, 11, 279– 290 First citation in articleCrossref Medline, Google Scholar

  • Vendruscolo, L. F. (2006). A QTL on rat chromosome 7 modulates prepulse inhibition, a neuro behavioral trait of ADHD, in a Lewis x SHR intercross. Behavioral and Brain Functions, 2, (1 21– First citation in articleGoogle Scholar

  • Walitza, S. , Renner, T. J. , Dempfle, A. , Konrad, K. , Wewetzer, C. , Halbach, A. , Herpertz-Dahlmann, B. , Remschmidt, H. , Smidt, J. , Linder, M. , Flierl, L. , Knolker, U. , Friedel, S. , Schafer, H. , Gross, C. , Hebebrand, J. , Warnke, A. , Lesch, K. P. (2005). Transmission disequilibrium of polymorphic variants in the tryptophan hydroxylase-2 gene in attention-deficit/hyperactivity disorder. Molecular Psychiatry, 10, (12) 1126– 1132 First citation in articleCrossref, Google Scholar

  • Weinshenker, D. , Miller, N. S. , Blizinsky, K. , Laughlin, M. L. , Palmiter, R. D. (2002). Mice with chronic norepinephrine deficiency resemble amphetamine-sensitized animals. Proceedings of the National Academy of Science USA, 99, 13873– 13877 First citation in articleCrossref Medline, Google Scholar

  • Williams, R. W. , Flaherty, L. , Threadgill, D. W. (2003). The math of making mutant mice. Genes, Brain, and Behavior, 2, 191– 200 First citation in articleCrossref Medline, Google Scholar

  • Xu, M. , Hu, X. T. , Cooper, D. C. , Moratalla, R. , Graybiel, A. M. , White, F. J. , Tonegawa, S. (1994). Elimination of cocaine-induced hyperactivity and dopamine-mediated neurophysiological effects in dopamine D1 receptor mutant mice. Cell, 79, 945– 955 First citation in articleCrossref Medline, Google Scholar

  • Zoroglu, S. S. , Erdal, M. E. , Alasehirli, B. , Erdal, N. , Sivasli, E. , Tutkun, H. , Savas, H. A. , Herken, H. (2002). Significance of serotonin transporter gene 5-HTTLPR and variable number of tandem repeat polymorphism in attention deficit hyperactivity disorder. Neuropsychobiology, 45, 176– 181 First citation in articleCrossref Medline, Google Scholar