Human Genetics

, Volume 126, Issue 1, pp 51–90 | Cite as

Candidate gene studies of ADHD: a meta-analytic review

Review Article

Abstract

Quantitative genetic studies (i.e., twin and adoption studies) suggest that genetic influences contribute substantially to the development of attention deficit hyperactivity disorder (ADHD). Over the past 15 years, considerable efforts have been made to identify genes involved in the etiology of this disorder resulting in a large and often conflicting literature of candidate gene associations for ADHD. The first aim of the present study was to conduct a comprehensive meta-analytic review of this literature to determine which candidate genes show consistent evidence of association with childhood ADHD across studies. The second aim was to test for heterogeneity across studies in the effect sizes for each candidate gene as its presence might suggest moderating variables that could explain inconsistent results. Significant associations were identified for several candidate genes including DAT1, DRD4, DRD5, 5HTT, HTR1B, and SNAP25. Further, significant heterogeneity was observed for the associations between ADHD and DAT1, DRD4, DRD5, DBH, ADRA2A, 5HTT, TPH2, MAOA, and SNAP25, suggesting that future studies should explore potential moderators of these associations (e.g., ADHD subtype diagnoses, gender, exposure to environmental risk factors). We conclude with a discussion of these findings in relation to emerging themes relevant to future studies of the genetics of ADHD.

References

  1. Achenbach TM, Edelbrock CS (1979) The child behavior profile: II. Boys aged 12–16 and girls aged 6–11 and 12–16. J Consult Clin Psychol 47:223–233PubMedCrossRefGoogle Scholar
  2. American Psychiatric Association (2000) Diagnostic and statistical manual of mental disorders, 4th edn. American Psychiatric Association, Washington, DCGoogle Scholar
  3. Andersen PH, Gingrich JA, Bates MD, Dearry A, Falardeau P, Senogles SE, Caron MG (1990) Dopamine receptor subtypes: beyond the D1/D2 classification. Trends Pharmacol Sci 11:231–236PubMedCrossRefGoogle Scholar
  4. Andrews GD, Lavin A (2006) Methylphenidate increases cortical excitability via activation of alpha-2 noradrenergic receptors. Neuropsychopharmacology 31:594–601PubMedCrossRefGoogle Scholar
  5. Arcos-Burgos M, Castellanos FX, Konecki D, Lopera F, Pineda D, Palacio JD, Rapoport JL, Berg K, Bailey-Wilson J, Muenke M (2004a) Pedigree disequilibrium test (PDT) replicates association and linkage between DRD4 and ADHD in multigenerational and extended pedigrees from a genetic isolate. Mol Psychiatry 9:252–259PubMedCrossRefGoogle Scholar
  6. Arcos-Burgos M, Castellanos FX, Pineda D, Lopera F, Palacio JD, Palacio LG, Rapoport JL, Berg K, Bailey-Wilson JE, Muenke M (2004b) Attention-deficit/hyperactivity disorder in a population isolate: linkage to loci at 4q13.2, 5q33.3, 11q22, and 17p11. Am J Hum Genet 75:998–1014PubMedCrossRefGoogle Scholar
  7. Arnsten AF (2006) Fundamentals of attention-deficit/hyperactivity disorder: circuits and pathways. J Clin Psychiatry 67(Suppl 8):7–12PubMedGoogle Scholar
  8. Arnsten AF, Li BM (2005) Neurobiology of executive functions: catecholamine influences on prefrontal cortical functions. Biol Psychiatry 57:1377–1384PubMedCrossRefGoogle Scholar
  9. Asghari V, Schoots O, van Kats S, Ohara K, Jovanovic V, Guan HC, Bunzow JR, Petronis A, Van Tol HH (1994) Dopamine D4 receptor repeat: analysis of different native and mutant forms of the human and rat genes. Mol Pharmacol 46:364–373PubMedGoogle Scholar
  10. Asghari V, Sanyal S, Buchwaldt S, Paterson A, Jovanovic V, Van Tol HH (1995) Modulation of intracellular cyclic AMP levels by different human dopamine D4 receptor variants. J Neurochem 65:1157–1165PubMedGoogle Scholar
  11. Asherson P, Brookes K, Franke B, Chen W, Gill M, Ebstein RP, Buitelaar J, Banaschewski T, Sonuga-Barke E, Eisenberg J, Manor I, Miranda A, Oades RD, Roeyers H, Rothenberger A, Sergeant J, Steinhausen HC, Faraone SV (2007) Confirmation that a specific haplotype of the dopamine transporter gene is associated with combined-type ADHD. Am J Psychiatry 164:674–677PubMedCrossRefGoogle Scholar
  12. Bakker SC, van der Meulen EM, Oteman N, Schelleman H, Pearson PL, Buitelaar JK, Sinke RJ (2005) DAT1, DRD4, and DRD5 polymorphisms are not associated with ADHD in Dutch families. Am J Med Genet B 132B:50–52CrossRefGoogle Scholar
  13. Banerjee E, Sinha S, Chatterjee A, Gangopadhyay PK, Singh M, Nandagopal K (2006) A family-based study of Indian subjects from Kolkata reveals allelic association of the serotonin transporter intron-2 (STin2) polymorphism and attention-deficit-hyperactivity disorder (ADHD). Am J Med Genet B 141B:361–366CrossRefGoogle Scholar
  14. Banoei MM, Majidizadeh T, Shirazi E, Moghimi N, Ghadiri M, Najmabadi H, Ohadi M (2008) No association between the DAT1 10-repeat allele and ADHD in the Iranian population. Am J Med Genet B 147B:110–111CrossRefGoogle Scholar
  15. Barr CL, Wigg K, Malone M, Schachar R, Tannock R, Roberts W, Kennedy JL (1999) Linkage study of catechol-O-methyltransferase and attention-deficit hyperactivity disorder. Am J Med Genet 88:710–713PubMedCrossRefGoogle Scholar
  16. Barr CL, Wigg KG, Feng Y, Zai G, Malone M, Roberts W, Schachar R, Tannock R, Kennedy JL (2000a) Attention-deficit hyperactivity disorder and the gene for the dopamine D5 receptor. Mol Psychiatry 5:548–551PubMedCrossRefGoogle Scholar
  17. Barr CL, Wigg KG, Wu J, Zai C, Bloom S, Tannock R, Roberts W, Malone M, Schachar R, Kennedy JL (2000b) Linkage study of two polymorphisms at the dopamine D3 receptor gene and attention-deficit hyperactivity disorder. Am J Med Genet 96:114–117PubMedCrossRefGoogle Scholar
  18. Barr CL, Feng Y, Wigg KG, Schachar R, Tannock R, Roberts W, Malone M, Kennedy JL (2001) 5′-untranslated region of the dopamine D4 receptor gene and attention-deficit hyperactivity disorder. Am J Med Genet 105:84–90PubMedCrossRefGoogle Scholar
  19. Barr CL, Kroft J, Feng Y, Wigg K, Roberts W, Malone M, Ickowicz A, Schachar R, Tannock R, Kennedy JL (2002) The norepinephrine transporter gene and attention-deficit hyperactivity disorder. Am J Med Genet 114:255–259PubMedCrossRefGoogle Scholar
  20. Battersby S, Ogilvie AD, Blackwood DH, Shen S, Muqit MM, Muir WJ, Teague P, Goodwin GM, Harmar AJ (1999) Presence of multiple functional polyadenylation signals and a single nucleotide polymorphism in the 3′ untranslated region of the human serotonin transporter gene. J Neurochem 72:1384–1388PubMedCrossRefGoogle Scholar
  21. Becker K, El-Faddagh M, Schmidt MH, Esser G, Laucht M (2008) Interaction of dopamine transporter genotype with prenatal smoke exposure on ADHD symptoms. J Pediatr 152:263–269PubMedCrossRefGoogle Scholar
  22. Beischlag TV, Marchese A, Meador-Woodruff JH, Damask SP, O’Dowd BF, Tyndale RF, van Tol HH, Seeman P, Niznik HB (1995) The human dopamine D5 receptor gene: cloning and characterization of the 5′-flanking and promoter region. Biochemistry (Mosc) 34:5960–5970CrossRefGoogle Scholar
  23. Beitchman J, Davidge KM, Kennedy JL, Atkinson L, Lee V, Shapiro S, Douglas L (2003) The serotonin transporter gene in aggressive children with and without ADHD and nonaggressive matched controls. Ann N Y Acad Sci 1008:248–251PubMedCrossRefGoogle Scholar
  24. Bellgrove MA, Hawi Z, Lowe N, Kirley A, Robertson IH, Gill M (2005) DRD4 gene variants and sustained attention in attention deficit hyperactivity disorder (ADHD): effects of associated alleles at the VNTR and -521 SNP. Am J Med Genet B 136B:81–86CrossRefGoogle Scholar
  25. Beninger RJ, Banasikowski TJ (2008) Dopaminergic mechanism of reward-related incentive learning: focus on the dopamine D(3) receptor. Neurotox Res 14:57–70PubMedGoogle Scholar
  26. Benjamin J, Li L, Patterson C, Greenberg B, Murphy D, Hamer D (1996) Population and familial association between the D4 dopamine receptor gene and measures of Novelty Seeking. Nat Genet 12:81–84PubMedCrossRefGoogle Scholar
  27. Bhaduri N, Mukhopadhyay K (2006) Lack of significant association between −1021C → T polymorphism in the dopamine beta hydroxylase gene and attention deficit hyperactivity disorder. Neurosci Lett 402:12–16PubMedCrossRefGoogle Scholar
  28. Bhaduri N, Das M, Sinha S, Chattopadhyay A, Gangopadhyay PK, Chaudhuri K, Singh M, Mukhopadhyay K (2006) Association of dopamine D4 receptor (DRD4) polymorphisms with attention deficit hyperactivity disorder in Indian population. Am J Med Genet B 141B:61–66CrossRefGoogle Scholar
  29. Biederman J, Faraone SV (2002) Current concepts on the neurobiology of Attention-Deficit/Hyperactivity Disorder. J Attent Disorders 6(Suppl 1):S7–S16Google Scholar
  30. Biederman J, Kim JW, Doyle AE, Mick E, Fagerness J, Smoller JW, Faraone SV (2008) Sexually dimorphic effects of four genes (COMT, SLC6A2, MAOA, SLC6A4) in genetic associations of ADHD: a preliminary study. Am J Med Genet B 147B:1511–1518CrossRefGoogle Scholar
  31. Blum K, Noble EP, Sheridan PJ, Montgomery A, Ritchie T, Jagadeeswaran P, Nogami H, Briggs AH, Cohn JB (1990) Allelic association of human dopamine D2 receptor gene in alcoholism. JAMA 263:2055–2060PubMedCrossRefGoogle Scholar
  32. Bobb AJ, Addington AM, Sidransky E, Gornick MC, Lerch JP, Greenstein DK, Clasen LS, Sharp WS, Inoff-Germain G, Wavrant-De Vrieze F, Arcos-Burgos M, Straub RE, Hardy JA, Castellanos FX, Rapoport JL (2005) Support for association between ADHD and two candidate genes: NET1 and DRD1. Am J Med Genet B 134B:67–72CrossRefGoogle Scholar
  33. Bowden CL, Deutsch CK, Swanson JM (1988) Plasma dopamine-beta-hydroxylase and platelet monoamine oxidase in attention deficit disorder and conduct disorder. J Am Acad Child Adolesc Psychiatry 27:171–174PubMedCrossRefGoogle Scholar
  34. Brookes KJ, Xu X, Chen CK, Huang YS, Wu YY, Asherson P (2005) No evidence for the association of DRD4 with ADHD in a Taiwanese population within-family study. BMC Med Genet 6:31PubMedCrossRefGoogle Scholar
  35. Brookes K, Xu X, Chen W, Zhou K, Neale B, Lowe N, Aneey R, Franke B, Gill M, Ebstein R, Buitelaar J, Sham P, Campbell D, Knight J, Andreou P, Altink M, Arnold R, Boer F, Buschgens C, Butler L, Christiansen H, Feldman L, Fleischman K, Fliers E, Howe-Forbes R, Goldfarb A, Heise A, Gabriels I, Korn-Lubetzki I, Marco R, Medad S, Minderaa R, Mulas F, Muller U, Mulligan A, Rabin K, Rommelse N, Sethna V, Sorohan J, Uebel H, Psychogiou L, Weeks A, Barrett R, Craig I, Banaschewski T, Sonuga-Barke E, Eisenberg J, Kuntsi J, Manor I, McGuffin P, Miranda A, Oades RD, Plomin R, Roeyers H, Rothenberger A, Sergeant J, Steinhausen HC, Taylor E, Thompson M, Faraone SV, Asherson P, Johansson L (2006a) The analysis of 51 genes in DSM-IV combined type attention deficit hyperactivity disorder: association signals in DRD4, DAT1 and 16 other genes. Mol Psychiatry 11:934–953PubMedCrossRefGoogle Scholar
  36. Brookes KJ, Mill J, Guindalini C, Curran S, Xu X, Knight J, Chen CK, Huang YS, Sethna V, Taylor E, Chen W, Breen G, Asherson P (2006b) A common haplotype of the dopamine transporter gene associated with attention-deficit/hyperactivity disorder and interacting with maternal use of alcohol during pregnancy. Arch Gen Psychiatry 63:74–81PubMedCrossRefGoogle Scholar
  37. Brookes KJ, Neale BM, Sugden K, Khan N, Asherson P, D’Souza UM (2007) Relationship between VNTR polymorphisms of the human dopamine transporter gene and expression in post-mortem midbrain tissue. Am J Med Genet B 144B:1070–1078CrossRefGoogle Scholar
  38. Brookes KJ, Xu X, Anney R, Franke B, Zhou K, Chen W, Banaschewski T, Buitelaar J, Ebstein R, Eisenberg J, Gill M, Miranda A, Oades RD, Roeyers H, Rothenberger A, Sergeant J, Sonuga-Barke E, Steinhausen HC, Taylor E, Faraone SV, Asherson P (2008) Association of ADHD with genetic variants in the 5′-region of the dopamine transporter gene: evidence for allelic heterogeneity. Am J Med Genet B 147B:1519–1523CrossRefGoogle Scholar
  39. Brophy K, Hawi Z, Kirley A, Fitzgerald M, Gill M (2002) Synaptosomal-associated protein 25 (SNAP-25) and attention deficit hyperactivity disorder (ADHD): evidence of linkage and association in the Irish population. Mol Psychiatry 7:913–917PubMedCrossRefGoogle Scholar
  40. Brunner D, Hen R (1997) Insights into the neurobiology of impulsive behavior from serotonin receptor knockout mice. Ann N Y Acad Sci 836:81–105PubMedCrossRefGoogle Scholar
  41. Brunner HG, Nelen M, Breakefield XO, Ropers HH, van Oost BA (1993) Abnormal behavior associated with a point mutation in the structural gene for monoamine oxidase A. Science 262:578–580PubMedCrossRefGoogle Scholar
  42. Carrasco X, Rothhammer P, Moraga M, Henriquez H, Aboitiz F, Rothhammer F (2004) Presence of DRD4/7R and DAT1/10R allele in Chilean family members with attention deficit hyperactivity disorder. Rev Med Chil 132:1047–1052PubMedGoogle Scholar
  43. Carrasco X, Rothhammer P, Moraga M, Henriquez H, Chakraborty R, Aboitiz F, Rothhammer F (2006) Genotypic interaction between DRD4 and DAT1 loci is a high risk factor for attention-deficit/hyperactivity disorder in Chilean families. Am J Med Genet B 141B:51–54CrossRefGoogle Scholar
  44. Cases O, Lebrand C, Giros B, Vitalis T, De Maeyer E, Caron MG, Price DJ, Gaspar P, Seif I (1998) Plasma membrane transporters of serotonin, dopamine, and norepinephrine mediate serotonin accumulation in atypical locations in the developing brain of monoamine oxidase A knock-outs. J Neurosci 18:6914–6927PubMedGoogle Scholar
  45. Caspi A, McClay J, Moffitt TE, Mill J, Martin J, Craig IW, Taylor A, Poulton R (2002) Role of genotype in the cycle of violence in maltreated children. Science 297:851–854PubMedCrossRefGoogle Scholar
  46. Chakravarti A (1999) Population genetics—making sense out of sequence. Nat Genet 21:56–60PubMedCrossRefGoogle Scholar
  47. Chang FM, Kidd JR, Livak KJ, Pakstis AJ, Kidd KK (1996) The world-wide distribution of allele frequencies at the human dopamine D4 receptor locus. Hum Genet 98:91–101PubMedCrossRefGoogle Scholar
  48. Chen K, Yang W, Grimsby J, Shih JC (1992) The human 5-HT2 receptor is encoded by a multiple intron-exon gene. Brain Res Mol Brain Res 14:20–26PubMedCrossRefGoogle Scholar
  49. Chen ZY, Patel PD, Sant G, Meng CX, Teng KK, Hempstead BL, Lee FS (2004) Variant brain-derived neurotrophic factor (BDNF) (Met66) alters the intracellular trafficking and activity-dependent secretion of wild-type BDNF in neurosecretory cells and cortical neurons. J Neurosci 24:4401–4411PubMedCrossRefGoogle Scholar
  50. Cheuk DK, Wong V (2006) Meta-analysis of association between a catechol-O-methyltransferase gene polymorphism and attention deficit hyperactivity disorder. Behav Genet 36:651–659PubMedCrossRefGoogle Scholar
  51. Cheuk DK, Li SY, Wong V (2006a) Exon 3 polymorphisms of dopamine D4 receptor (DRD4) gene and attention deficit hyperactivity disorder in Chinese children. Am J Med Genet B 141B:907–911CrossRefGoogle Scholar
  52. Cheuk DK, Li SY, Wong V (2006b) No association between VNTR polymorphisms of dopamine transporter gene and attention deficit hyperactivity disorder in Chinese children. Am J Med Genet B 141B:123–125CrossRefGoogle Scholar
  53. Cho SC, Kim JW, Kim BN, Hwang JW, Park M, Kim SA, Cho DY, Yoo HJ, Chung US, Son JW, Park TW (2008a) No evidence of an association between norepinephrine transporter gene polymorphisms and attention deficit hyperactivity disorder: a family-based and case-control association study in a Korean sample. Neuropsychobiology 57:131–138PubMedCrossRefGoogle Scholar
  54. Cho SC, Kim JW, Kim BN, Hwang JW, Park M, Kim SA, Cho DY, Yoo HJ, Chung US, Son JW, Park TW (2008b) Possible association of the alpha-2A-adrenergic receptor gene with response time variability in attention deficit hyperactivity disorder. Am J Med Genet B 147B:957–963CrossRefGoogle Scholar
  55. Choi TK, Lee HS, Kim JW, Park TW, Song DH, Yook KW, Lee SH, Kim JI, Suh SY (2007) Support for the MnlI polymorphism of SNAP25; a Korean ADHD case-control study. Mol Psychiatry 12:224–226PubMedCrossRefGoogle Scholar
  56. Ciliax BJ, Drash GW, Staley JK, Haber S, Mobley CJ, Miller GW, Mufson EJ, Mash DC, Levey AI (1999) Immunocytochemical localization of the dopamine transporter in human brain. J Comp Neurol 409:38–56PubMedCrossRefGoogle Scholar
  57. Comings DE, Comings BG, Muhleman D, Dietz G, Shahbahrami B, Tast D, Knell E, Kocsis P, Baumgarten R, Kovacs BW et al (1991) The dopamine D2 receptor locus as a modifying gene in neuropsychiatric disorders. JAMA 266:1793–1800PubMedCrossRefGoogle Scholar
  58. Comings DE, Wu S, Chiu C, Ring RH, Gade R, Ahn C, MacMurray JP, Dietz G, Muhleman D (1996) Polygenic inheritance of Tourette syndrome, stuttering, attention deficit hyperactivity, conduct, and oppositional defiant disorder: the additive and subtractive effect of the three dopaminergic genes—DRD2, D beta H, and DAT1. Am J Med Genet 67:264–288PubMedCrossRefGoogle Scholar
  59. Cook E Jr, Stein M, Krasowski M, Cox N, Olkon D, Kieffer J, Leventhal B (1995) Association of attention-deficit disorder and the dopamine transporter gene. Am J Hum Genet 56:993–998PubMedGoogle Scholar
  60. Cornish KM, Manly T, Savage R, Swanson J, Morisano D, Butler N, Grant C, Cross G, Bentley L, Hollis CP (2005) Association of the dopamine transporter (DAT1) 10/10-repeat genotype with ADHD symptoms and response inhibition in a general population sample. Mol Psychiatry 10:686–698PubMedCrossRefGoogle Scholar
  61. Craig SP, Buckle VJ, Lamouroux A, Mallet J, Craig IW (1988) Localization of the human dopamine beta hydroxylase (DBH) gene to chromosome 9q34. Cytogenet Cell Genet 48:48–50PubMedCrossRefGoogle Scholar
  62. Craig SP, Boularand S, Darmon MC, Mallet J, Craig IW (1991) Localization of human tryptophan hydroxylase (TPH) to chromosome 11p15.3–p14 by in situ hybridization. Cytogenet Cell Genet 56:157–159PubMedCrossRefGoogle Scholar
  63. Cubells JF, Kranzler HR, McCance-Katz E, Anderson GM, Malison RT, Price LH, Gelernter J (2000) A haplotype at the DBH locus, associated with low plasma dopamine beta-hydroxylase activity, also associates with cocaine-induced paranoia. Mol Psychiatry 5:56–63PubMedCrossRefGoogle Scholar
  64. Curran S, Mill J, Sham P, Rijsdijk F, Marusic K, Taylor E, Asherson P (2001a) QTL association analysis of the DRD4 exon 3 VNTR polymorphism in a population sample of children screened with a parent rating scale for ADHD symptoms. Am J Med Genet 105:387–393PubMedCrossRefGoogle Scholar
  65. Curran S, Mill J, Tahir E, Kent L, Richards S, Gould A, Huckett L, Sharp J, Batten C, Fernando S, Ozbay F, Yazgan Y, Simonoff E, Thompson M, Taylor E, Asherson P (2001b) Association study of a dopamine transporter polymorphism and attention deficit hyperactivity disorder in UK and Turkish samples. Mol Psychiatry 6:425–428PubMedCrossRefGoogle Scholar
  66. Curran S, Purcell S, Craig I, Asherson P, Sham P (2005) The serotonin transporter gene as a QTL for ADHD. Am J Med Genet B 134B:42–47CrossRefGoogle Scholar
  67. D’Souza UM, Russ C, Tahir E, Mill J, McGuffin P, Asherson PJ, Craig IW (2004) Functional effects of a tandem duplication polymorphism in the 5′ flanking region of the DRD4 gene. Biol Psychiatry 56:691–697PubMedCrossRefGoogle Scholar
  68. Daly G, Hawi Z, Fitzgerald M, Gill M (1999) Mapping susceptibility loci in attention deficit hyperactivity disorder: preferential transmission of parental alleles at DAT1, DBH and DRD5 to affected children. Mol Psychiatry 4:192–196PubMedCrossRefGoogle Scholar
  69. Das M, Mukhopadhyay K (2007) DAT1 3′-UTR 9R allele: preferential transmission in Indian children with attention deficit hyperactivity disorder. Am J Med Genet B 144B:826–829CrossRefGoogle Scholar
  70. Das M, Bhowmik AD, Sinha S, Chattopadhyay A, Chaudhuri K, Singh M, Mukhopadhyay K (2006) MAOA promoter polymorphism and attention deficit hyperactivity disorder (ADHD) in indian children. Am J Med Genet B 141B:637–642CrossRefGoogle Scholar
  71. Deckert J, Catalano M, Syagailo YV, Bosi M, Okladnova O, Di Bella D, Nothen MM, Maffei P, Franke P, Fritze J, Maier W, Propping P, Beckmann H, Bellodi L, Lesch KP (1999) Excess of high activity monoamine oxidase A gene promoter alleles in female patients with panic disorder. Hum Mol Genet 8:621–624PubMedCrossRefGoogle Scholar
  72. Demchyshyn L, Sunahara RK, Miller K, Teitler M, Hoffman BJ, Kennedy JL, Seeman P, Van Tol HH, Niznik HB (1992) A human serotonin 1D receptor variant (5HT1D beta) encoded by an intronless gene on chromosome 6. Proc Natl Acad Sci USA 89:5522–5526PubMedCrossRefGoogle Scholar
  73. Dempster EL, Mill J, Craig IW, Collier DA (2006) The quantification of COMT mRNA in post mortem cerebellum tissue: diagnosis, genotype, methylation and expression. BMC Med Genet 7:10PubMedCrossRefGoogle Scholar
  74. Deupree JD, Smith SD, Kratochvil CJ, Bohac D, Ellis CR, Polaha J, Bylund DB, Team UCAR (2006) Possible involvement of alpha-2A adrenergic receptors in attention deficit hyperactivity disorder: radioligand binding and polymorphism studies. Am J Med Genet B 141:877–884CrossRefGoogle Scholar
  75. 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. Am J Med Genet B 134B:110–114CrossRefGoogle Scholar
  76. Doucette-Stamm LA, Blakely DJ, Tian J, Mockus S, Mao JI (1995) Population genetic study of the human dopamine transporter gene (DAT1). Genet Epidemiol 12:303–308PubMedCrossRefGoogle Scholar
  77. Driscoll DA, Spinner NB, Budarf ML, McDonald-McGinn DM, Zackai EH, Goldberg RB, Shprintzen RJ, Saal HM, Zonana J, Jones MC et al (1992) Deletions and microdeletions of 22q11.2 in velo-cardio-facial syndrome. Am J Med Genet 44:261–268PubMedCrossRefGoogle Scholar
  78. Dwivedi Y, Pandey GN (1998) Quantitation of 5HT2A receptor mRNA in human postmortem brain using competitive RT-PCR. NeuroReport 9:3761–3765PubMedCrossRefGoogle Scholar
  79. Ebstein R, Novick O, Umansky R, Priel B, Osher Y, Blaine D, Bennett E, Nemanov L, Katz M, Belmaker R (1996) Dopamine D4 receptor (DRD4) exon III polymorphism associated with the human personality trait of Novelty Seeking. Nat Genet 12:78–80PubMedCrossRefGoogle Scholar
  80. Egan MF, Kojima M, Callicott JH, Goldberg TE, Kolachana BS, Bertolino A, Zaitsev E, Gold B, Goldman D, Dean M, Lu B, Weinberger DR (2003) The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function. Cell 112:257–269PubMedCrossRefGoogle Scholar
  81. Eisenberg J, Mei-Tal G, Steinberg A, Tartakovsky E, Zohar A, Gritsenko I, Nemanov L, Ebstein RP (1999) Haplotype relative risk study of catechol-O-methyltransferase (COMT) and attention deficit hyperactivity disorder (ADHD): association of the high-enzyme activity Val allele with ADHD impulsive-hyperactive phenotype. Am J Med Genet 88:497–502PubMedCrossRefGoogle Scholar
  82. El-Faddagh M, Laucht M, Maras A, Vohringer L, Schmidt MH (2004) Association of dopamine D4 receptor (DRD4) gene with attention-deficit/hyperactivity disorder (ADHD) in a high-risk community sample: a longitudinal study from birth to 11 years of age. J Neural Transm 111:883–889PubMedCrossRefGoogle Scholar
  83. Erdmann J, Shimron-Abarbanell D, Rietschel M, Albus M, Maier W, Korner J, Bondy B, Chen K, Shih JC, Knapp M, Propping P, Nothen MM (1996) Systematic screening for mutations in the human serotonin-2A (5-HT2A) receptor gene: identification of two naturally occurring receptor variants and association analysis in schizophrenia. Hum Genet 97:614–619PubMedCrossRefGoogle Scholar
  84. Eubanks JH, Djabali M, Selleri L, Grandy DK, Civelli O, McElligott DL, Evans GA (1992) Structure and linkage of the D2 dopamine receptor and neural cell adhesion molecule genes on human chromosome 11q23. Genomics 14:1010–1018PubMedCrossRefGoogle Scholar
  85. Evangelou E, Trikalinos TA, Salanti G, Ioannidis JP (2006) Family-based versus unrelated case-control designs for genetic associations. PLoS Genet 2:e123PubMedCrossRefGoogle Scholar
  86. Faraone SV, Asherson P (2005) The molecular genetics of ADHD: a view from the IMAGE Project. Psychiatric Times 22Google Scholar
  87. Faraone SV, Khan SA (2006) Candidate gene studies of attention-deficit/hyperactivity disorder. J Clin Psychiatry 67(Suppl 8):13–20PubMedGoogle Scholar
  88. Faraone S, Biederman J, Weiffenbach B, Keith T, Chu M, Weaver A, Spencer T, Wilens T, Frazier J, Cleves M, Sakai J (1999) Dopamine D4 gene 7-repeat allele and attention deficit hyperactivity disorder. Am J Psychiatry 156:768–770PubMedGoogle Scholar
  89. Faraone S, Doyle A, Mick E, Biederman J (2001) Meta-analysis of the association between the 7-repeat allele of the dopamine D(4) receptor gene and attention deficit hyperactivity disorder. Am J Psychiatry 158:1052–1057PubMedCrossRefGoogle Scholar
  90. Faraone S, Perlis R, Doyle A, Smoller J, Goralnick J, Holmgren M, Sklar P (2005) Molecular genetics of Attention-Deficit/Hyperactivity Disorder. Biol Psychiatry 57:1313–1323PubMedCrossRefGoogle Scholar
  91. Feng Y, Crosbie J, Wigg K, Pathare T, Ickowicz A, Schachar R, Tannock R, Roberts W, Malone M, Swanson J, Kennedy JL, Barr CL (2005a) The SNAP25 gene as a susceptibility gene contributing to attention-deficit hyperactivity disorder. Mol Psychiatry 10:998–1005 973PubMedCrossRefGoogle Scholar
  92. Feng Y, Wigg KG, Makkar R, Ickowicz A, Pathare T, Tannock R, Roberts W, Malone M, Kennedy JL, Schachar R, Barr CL (2005b) Sequence variation in the 3′-untranslated region of the dopamine transporter gene and attention-deficit hyperactivity disorder (ADHD). Am J Med Genet B 139B:1–6CrossRefGoogle Scholar
  93. Fiskerstrand CE, Lovejoy EA, Quinn JP (1999) An intronic polymorphic domain often associated with susceptibility to affective disorders has allele dependent differential enhancer activity in embryonic stem cells. FEBS Lett 458:171–174PubMedCrossRefGoogle Scholar
  94. Floresco SB, Tse MT (2007) Dopaminergic regulation of inhibitory and excitatory transmission in the basolateral amygdala-prefrontal cortical pathway. J Neurosci 27:2045–2057PubMedCrossRefGoogle Scholar
  95. Frank Y, Pergolizzi RG, Perilla MJ (2004) Dopamine D4 receptor gene and attention deficit hyperactivity disorder. Pediatr Neurol 31:345–348PubMedCrossRefGoogle Scholar
  96. Franke B, Neale BM, Faraone SV (2009) Genome-wide association studies in ADHD. Hum Genet. doi:10.1007/s00439-009-0663-4
  97. Frankle WG, Huang Y, Hwang DR, Talbot PS, Slifstein M, Van Heertum R, Abi-Dargham A, Laruelle M (2004) Comparative evaluation of serotonin transporter radioligands 11C-DASB and 11C-McN 5652 in healthy humans. J Nucl Med 45:682–694PubMedGoogle Scholar
  98. Friedel S, Horro FF, Wermter AK, Geller F, Dempfle A, Reichwald K, Smidt J, Bronner G, Konrad K, Herpertz-Dahlmann B, Warnke A, Hemminger U, Linder M, Kiefl H, Goldschmidt HP, 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. Am J Med Genet B 132B:96–99CrossRefGoogle Scholar
  99. Friedel S, Saar K, Sauer S, Dempfle A, Walitza S, Renner T, Romanos M, Freitag C, Seitz C, Palmason H, Scherag A, Windemuth-Kieselbach C, Schimmelmann BG, Wewetzer C, Meyer J, Warnke A, Lesch KP, Reinhardt R, Herpertz-Dahlmann B, Linder M, Hinney A, Remschmidt H, Schafer H, Konrad K, Hubner N, Hebebrand J (2007) Association and linkage of allelic variants of the dopamine transporter gene in ADHD. Mol Psychiatry 12:923–933PubMedCrossRefGoogle Scholar
  100. Fung YK, Lau YS (1988) Receptor mechanisms of nicotine-induced locomotor hyperactivity in chronic nicotine-treated rats. Eur J Pharmacol 152:263–271PubMedCrossRefGoogle Scholar
  101. Gainetdinov RR, Wetsel WC, Jones SR, Levin ED, Jaber M, Caron MG (1999) Role of serotonin in the paradoxical calming effect of psychostimulants on hyperactivity. Science 283:397–401PubMedCrossRefGoogle Scholar
  102. Galili-Weisstub E, Segman RH (2003) Attention deficit and hyperactivity disorder: review of genetic association studies. Israel J Psychiatry 40:57–66Google Scholar
  103. Gelernter J, Kennedy JL, van Tol HH, Civelli O, Kidd KK (1992) The D4 dopamine receptor (DRD4) maps to distal 11p close to HRAS. Genomics 13:208–210PubMedCrossRefGoogle Scholar
  104. Gelernter J, Kruger S, Pakstis AJ, Pacholczyk T, Sparkes RS, Kidd KK, Amara S (1993) Assignment of the norepinephrine transporter protein (NET1) locus to chromosome 16. Genomics 18:690–692PubMedCrossRefGoogle Scholar
  105. Gelernter J, Pakstis AJ, Kidd KK (1995) Linkage mapping of serotonin transporter protein gene SLC6A4 on chromosome 17. Hum Genet 95:677–680PubMedCrossRefGoogle Scholar
  106. Genro JP, Zeni C, Polanczyk GV, Roman T, Rohde LA, Hutz MH (2007) A promoter polymorphism (−839 C → T) at the dopamine transporter gene is associated with attention deficit/hyperactivity disorder in Brazilian children. Am J Med Genet B 144B:215–219CrossRefGoogle Scholar
  107. Genro JP, Polanczyk GV, Zeni C, Oliveira AS, Roman T, Rohde LA, Hutz MH (2008) A common haplotype at the dopamine transporter gene 5′ region is associated with attention-deficit/hyperactivity disorder. Am J Med Genet B 147B:1568–1575CrossRefGoogle Scholar
  108. Giros B, Jaber M, Jones SR, Wightman RM, Caron MG (1996) Hyperlocomotion and indifference to cocaine and amphetamine in mice lacking the dopamine transporter. Nature 379:606–612PubMedCrossRefGoogle Scholar
  109. Gogos JA, 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. Proc Natl Acad Sci USA 95:9991–9996PubMedCrossRefGoogle Scholar
  110. Gornick MC, Addington A, Shaw P, Bobb AJ, Sharp W, Greenstein D, Arepalli S, Castellanos FX, Rapoport JL (2007) Association of the dopamine receptor D4 (DRD4) gene 7-repeat allele with children with attention-deficit/hyperactivity disorder (ADHD): an update. Am J Med Genet B 144B:379–382CrossRefGoogle Scholar
  111. Grady S, Marks MJ, Wonnacott S, Collins AC (1992) Characterization of nicotinic receptor-mediated [3H] dopamine release from synaptosomes prepared from mouse striatum. J Neurochem 59:848–856PubMedCrossRefGoogle Scholar
  112. Greenwood TA, Alexander M, Keck PE, McElroy S, Sadovnick AD, Remick RA, Shaw SH, Kelsoe JR (2002) Segmental linkage disequilibrium within the dopamine transporter gene. Mol Psychiatry 7:165–173PubMedCrossRefGoogle Scholar
  113. Guan L, Wang B, Chen Y, Yang L, Li J, Qian Q, Wang Z, Faraone SV, Wang Y (2008) A high-density single-nucleotide polymorphism screen of 23 candidate genes in attention deficit hyperactivity disorder: suggesting multiple susceptibility genes among Chinese Han population. Mol Psychiatry 14:546–554PubMedCrossRefGoogle Scholar
  114. Guillin O, Diaz J, Carroll P, Griffon N, Schwartz JC, Sokoloff P (2001) BDNF controls dopamine D3 receptor expression and triggers behavioural sensitization. Nature 411:86–89PubMedCrossRefGoogle Scholar
  115. Guimares APM, Zeni C, Polanczyk GV, Genro JP, Roman T, Rohde LA, Hutz MH (2007) Serotonin genes and attention deficit/hyperactivity disorder in a Brazilian sample: preferential transmission of the HTR2A 452His allele to affected boys. Am J Med Genet B 144B:69–73CrossRefGoogle Scholar
  116. Guindalini C, Howard M, Haddley K, Laranjeira R, Collier D, Ammar N, Craig I, O’Gara C, Bubb VJ, Greenwood T, Kelsoe J, Asherson P, Murray RM, Castelo A, Quinn JP, Vallada H, Breen G (2006) A dopamine transporter gene functional variant associated with cocaine abuse in a Brazilian sample. Proc Natl Acad Sci USA 103:4552–4557PubMedCrossRefGoogle Scholar
  117. Hall FS, Drgonova J, Goeb M, Uhl GR (2003) Reduced behavioral effects of cocaine in heterozygous brain-derived neurotrophic factor (BDNF) knockout mice. Neuropsychopharmacology 28:1485–1490PubMedCrossRefGoogle Scholar
  118. Halperin JM, Newcorn JH, Schwartz ST, Sharma V, Siever LJ, Koda VH, Gabriel S (1997) Age-related changes in the association between serotonergic function and aggression in boys with ADHD. Biol Psychiatry 41:682–689PubMedCrossRefGoogle Scholar
  119. Hawi Z, McCarron M, Kirley A, Daly G, Fitzgerald M, Gill M (2000a) No association of the dopamine DRD4 receptor (DRD4) gene polymorphism with attention deficit hyperactivity disorder (ADHD) in the Irish population. Am J Med Genet 96:268–272PubMedCrossRefGoogle Scholar
  120. Hawi Z, Millar N, Daly G, Fitzgerald M, Gill M (2000b) No association between catechol-O-methyltransferase (COMT) gene polymorphism and attention deficit hyperactivity disorder (ADHD) in an Irish sample. Am J Med Genet 96:282–284PubMedCrossRefGoogle Scholar
  121. 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. Mol Psychiatry 6:420–424PubMedCrossRefGoogle Scholar
  122. Hawi Z, Dring M, Kirley A, Foley D, Kent L, Craddock N, Asherson P, Curran S, Gould A, Richards S, Lawson D, Pay H, Turic D, Langley K, Owen M, O’Donovan M, Thapar A, Fitzgerald M, Gill M (2002) Serotonergic system and attention deficit hyperactivity disorder (ADHD): a potential susceptibility locus at the 5-HT(1B) receptor gene in 273 nuclear families from a multi-centre sample. Mol Psychiatry 7:718–725PubMedCrossRefGoogle Scholar
  123. Hawi Z, Lowe N, Kirley A, Gruenhage F, Nothen M, Greenwood T, Kelsoe J, Fitzgerald M, Gill M (2003) Linkage disequilibrium mapping at DAT1, DRD5 and DBH narrows the search for ADHD susceptibility alleles at these loci. Mol Psychiatry 8:299–308PubMedCrossRefGoogle Scholar
  124. 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. Am J Hum Genet 77:958–965PubMedCrossRefGoogle Scholar
  125. 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. Mol Psychiatry 11:196–205PubMedCrossRefGoogle Scholar
  126. Heils A, Teufel A, Petri S, Stober G, Riederer P, Bengel D, Lesch KP (1996) Allelic variation of human serotonin transporter gene expression. J Neurochem 66:2621–2624PubMedGoogle Scholar
  127. Heinz A, Goldman D, Jones DW, Palmour R, Hommer D, Gorey JG, Lee KS, Linnoila M, Weinberger DR (2000) Genotype influences in vivo dopamine transporter availability in human striatum. Neuropsychopharmacology 22:133–139PubMedCrossRefGoogle Scholar
  128. Heiser P, Dempfle A, Friedel S, Konrad K, Hinney A, Kiefl H, Walitza S, Bettecken T, Saar K, Linder M, Warnke A, Herpertz-Dahlmann B, Schäfer H, Remschmidt H, Hebebrand J (2007) Family-based association study of serotonergic candidate genes and attention-deficit/hyperactivity disorder in a German sample. J Neural Transm 114:513–521PubMedCrossRefGoogle Scholar
  129. Hess EJ, Jinnah HA, Kozak CA, Wilson MC (1992) Spontaneous locomotor hyperactivity in a mouse mutant with a deletion including the Snap gene on chromosome 2. J Neurosci 12:2865–2874PubMedGoogle Scholar
  130. Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21:1539–1558PubMedCrossRefGoogle Scholar
  131. Hinshaw SP (1987) On the distinction between attentional deficits/hyperactivity and conduct problems/aggression in child psychopathology. Psychol Bull 101:443–463PubMedCrossRefGoogle Scholar
  132. Hoenicka J, Aragues M, Ponce G, Rodriguez-Jimenez R, Jimenez-Arriero MA, Palomo T (2007) From dopaminergic genes to psychiatric disorders. Neurotox Res 11:61–72PubMedGoogle Scholar
  133. Holmes J, Payton A, Barrett J, Hever T, Fitzpatrick H, Trumper A, Harrington R, McGuffin P, Owen M, Ollier W, Worthington J, Thapar A (2000) A family-based and case-control association study of the dopamine D4 receptor gene and dopamine transporter gene in attention deficit hyperactivity disorder. Mol Psychiatry 5:523–530PubMedCrossRefGoogle Scholar
  134. Hong J, Shu-Leong H, Tao X, Lap-Ping Y (1998) Distribution of catechol-O-methyltransferase expression in human central nervous system. NeuroReport 9:2861–2864PubMedGoogle Scholar
  135. Horger BA, Iyasere CA, Berhow MT, Messer CJ, Nestler EJ, Taylor JR (1999) Enhancement of locomotor activity and conditioned reward to cocaine by brain-derived neurotrophic factor. J Neurosci 19:4110–4122PubMedGoogle Scholar
  136. Housley DJ, Nikolas M, Venta PJ, Jernigan KA, Waldman ID, Nigg JT, Friderici KH (2009) SNP discovery and haplotype analysis in the segmentally duplicated DRD5 coding region. Ann Hum Genet (epub ahead of printGoogle Scholar
  137. Huang YS, Lin SK, Wu YY, Chao CC, Chen CK (2003) A family-based association study of attention-deficit hyperactivity disorder and dopamine D2 receptor TaqI A alleles Transmission disequilibrium testing of dopamine-related candidate gene polymorphisms in ADHD: confirmation of association of ADHD with DRD4 and DRD5. Chang Gung Med J 26:897–903PubMedGoogle Scholar
  138. Ichikawa M, Okamura-Oho Y, Okunishi R, Kanamori M, Suzuki H, Ritani A, Nitta H, Eguchi N, Urade Y, Hayashizaki Y (2005) Expression analysis of genes responsible for serotonin signaling in the brain. Neurobiol Dis 19:378–385PubMedCrossRefGoogle Scholar
  139. Ickowicz A, Feng Y, Wigg K, Quist J, Pathare T, Roberts W, Malone M, Schachar R, Tannock R, Kennedy JL, Barr CL (2007) The serotonin receptor HTR1B: gene polymorphisms in attention deficit hyperactivity disorder. Am J Med Genet B 144B:121–125CrossRefGoogle Scholar
  140. Internation HapMap Consortium (2003) The International HapMap Project. Nature 426:789–796CrossRefGoogle Scholar
  141. Ioannidis JP (2003) Genetic associations: false or true? Trends Mol Med 9:135–138PubMedCrossRefGoogle Scholar
  142. Ioannidis JP, Ntzani EE, Trikalinos TA, Contopoulos-Ioannidis DG (2001) Replication validity of genetic association studies. Nat Genet 29:306–309PubMedCrossRefGoogle Scholar
  143. Ioannidis JP, Trikalinos TA, Ntzani EE, Contopoulos-Ioannidis DG (2003) Genetic associations in large versus small studies: an empirical assessment. Lancet 361:567–571PubMedCrossRefGoogle Scholar
  144. Jacobsen LK, Staley JK, Zoghbi SS, Seibyl JP, Kosten TR, Innis RB, Gelernter J (2000) Prediction of dopamine transporter binding availability by genotype: a preliminary report. Am J Psychiatry 157:1700–1703PubMedCrossRefGoogle Scholar
  145. Jiang SD, Xin RN, Qian YP, Lin SC, Tang GM, Wang DY et al (1999) The relationship between attention-deficit hyperactivity disorder and dopamine transporter 1 gene. Chinese J Nerv Ment Dis 25:355–357Google Scholar
  146. Jiang S, Xin R, Lin S, Qian Y, Tang G, Wang D, Wu X (2001) Linkage studies between attention-deficit hyperactivity disorder and the monoamine oxidase genes. Am J Med Genet 105:783–788PubMedCrossRefGoogle Scholar
  147. Jiang H, Xie T, Ramsden DB, Ho SL (2003) Human catechol-O-methyltransferase down-regulation by estradiol. Neuropharmacology 45:1011–1018PubMedCrossRefGoogle Scholar
  148. Jiang SD, Wu XD, Zhang Y, Tang GM, Qian YP, Wang DX (2005) No association between attention-deficit hyperactivity disorder and catechol-O-methyltransferase gene in Chinese. Yi chuan Xue Bao 32:784–788PubMedGoogle Scholar
  149. Jin H, Oksenberg D, Ashkenazi A, Peroutka SJ, Duncan AM, Rozmahel R, Yang Y, Mengod G, Palacios JM, O’Dowd BF (1992) Characterization of the human 5-hydroxytryptamine1B receptor. J Biol Chem 267:5735–5738PubMedGoogle Scholar
  150. Kahn RS, Khoury J, Nichols WC, Lanphear BP (2003) Role of dopamine transporter genotype and maternal prenatal smoking in childhood hyperactive-impulsive, inattentive, and oppositional behaviors. J Pediatr 143:104–110PubMedCrossRefGoogle Scholar
  151. Kazeem GR, Farrall M (2005) Integrating case-control and TDT studies. Ann Hum Genet 69:329–335PubMedCrossRefGoogle Scholar
  152. Kebir O, Tabbane K, Sengupta S, Joober R (2009) Candidate genes and neuropsychological phenotypes in children with ADHD: review of association studies. J Psychiatry Neurosci 34:88–101PubMedGoogle Scholar
  153. Kent L, Middle F, Hawi Z, Fitzgerald M, Gill M, Feehan C, Craddock N (2001) Nicotinic acetylcholine receptor alpha4 subunit gene polymorphism and attention deficit hyperactivity disorder. Psychiatr Genet 11:37–40PubMedCrossRefGoogle Scholar
  154. 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. Mol Psychiatry 7:908–912PubMedCrossRefGoogle Scholar
  155. Kent L, Green E, Hawi Z, Kirley A, Dudbridge F, Lowe N, Raybould R, Langley K, Bray N, Fitzgerald M, Owen MJ, O’Donovan MC, Gill 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. Mol Psychiatry 10:939–943PubMedCrossRefGoogle Scholar
  156. Kereszturi E, Kiraly O, Csapo Z, Tarnok Z, Gadoros J, Sasvari-Szekely M, Nemoda Z (2007) Association between the 120-bp duplication of the dopamine D4 receptor gene and attention deficit hyperactivity disorder: genetic and molecular analyses. Am J Med Genet B 144B:231–236CrossRefGoogle Scholar
  157. Kieling C, Roman T, Doyle AE, Hutz MH, Rohde LA (2006) Association between DRD4 gene and performance of children with ADHD in a test of sustained attention. Biol Psychiatry 60:1163–1165PubMedCrossRefGoogle Scholar
  158. Kim SJ, Badner J, Cheon KA, Kim BN, Yoo HJ, Kim SJ, Cook E, Leventhal BL, Kim YS (2005a) Family-based association study of the serotonin transporter gene polymorphisms in Korean ADHD trios. Am J Med Genet B 139B:14–18CrossRefGoogle Scholar
  159. Kim YS, Leventhal BL, Kim SJ, Kim BN, Cheon KA, Yoo HJ, Badner J, Cook EH (2005b) Family-based association study of DAT1 and DRD4 polymorphism in Korean children with ADHD. Neurosci Lett 390:176–181PubMedCrossRefGoogle Scholar
  160. Kim CH, Hahn MK, Joung Y, Anderson SL, Steele AH, Mazei-Robinson MS, Gizer I, Teicher MH, Cohen BM, Robertson D, Waldman ID, Blakely RD, Kim KS (2006a) A polymorphism in the norepinephrine transporter gene alters promoter activity and is associated with attention-deficit hyperactivity disorder. Proc Natl Acad Sci USA 103:19164–19169PubMedCrossRefGoogle Scholar
  161. Kim JW, Kim BN, Cho SC (2006b) The dopamine transporter gene and the impulsivity phenotype in attention deficit hyperactivity disorder: a case-control association study in a Korean sample. J Psychiatr Res 40:730–737PubMedCrossRefGoogle Scholar
  162. Kim JW, Biederman J, Arbeitman L, Fagerness J, Doyle AE, Petty C, Perlis RH, Purcell S, Smoller JW, Faraone SV, Sklar P (2007) Investigation of variation in SNAP-25 and ADHD and relationship to co-morbid major depressive disorder. Am J Med Genet B 144B:781–790CrossRefGoogle Scholar
  163. Kim JW, Biederman J, McGrath CL, Doyle AE, Mick E, Fagerness J, Purcell S, Smoller JW, Sklar P, Faraone SV (2008) Further evidence of association between two NET single-nucleotide polymorphisms with ADHD. Mol Psychiatry 13:624–630 Epub 2007 Sep 18PubMedCrossRefGoogle Scholar
  164. Kirley A, Hawi Z, Daly G, McCarron M, Mullins C, Millar N, Waldman I, Fitzgerald M, Gill M (2002) Dopaminergic system genes in ADHD: toward a biological hypothesis. Neuropsychopharmacology 27:607–619PubMedGoogle Scholar
  165. Kopeckova M, Paclt I, Petrasek J, Pacltova D, Malikova M, Zagatova V (2008) Some ADHD polymorphisms (in genes DAT1, DRD2, DRD3, DBH, 5-HTT) in case-control study of 100 subjects 6–10 age. Neuroendocrinol Lett 29:246–251PubMedGoogle Scholar
  166. Kotler M, Manor I, Sever Y, Eisenberg J, Cohen H, Ebstein RP, Tyano S (2000) Failure to replicate an excess of the long dopamine D4 exon III repeat polymorphism in ADHD in a family-based study. Am J Med Genet 96:278–281PubMedCrossRefGoogle Scholar
  167. Kustanovich V, Merriman B, McGough J, McCracken JT, Smalley SL, Nelson SF (2003) Biased paternal transmission of SNAP-25 risk alleles in attention-deficit hyperactivity disorder. Mol Psychiatry 8:309–315PubMedCrossRefGoogle Scholar
  168. Kustanovich V, Ishii J, Crawford L, Yang M, McGough JJ, McCracken JT, Smalley SL, Nelson SF (2004) Transmission disequilibrium testing of dopamine-related candidate gene polymorphisms in ADHD: confirmation of association of ADHD with DRD4 and DRD5. Mol Psychiatry 9:711–717PubMedGoogle Scholar
  169. Laakso A, Pohjalainen T, Bergman J, Kajander J, Haaparanta M, Solin O, Syvalahti E, Hietala J (2005) The A1 allele of the human D2 dopamine receptor gene is associated with increased activity of striatal l-amino acid decarboxylase in healthy subjects. Pharmacogenet Genomics 15:387–391PubMedCrossRefGoogle Scholar
  170. LaHoste G, Swanson J, Wigal S, Glabe C, Wigal T, King N, Kennedy J (1996) Dopamine D4 receptor gene polymorphism is associated with attention deficit hyperactivity disorder. Mol Psychiatry 1:121–124PubMedGoogle Scholar
  171. Lan NC, Heinzmann C, Gal A, Klisak I, Orth U, Lai E, Grimsby J, Sparkes RS, Mohandas T, Shih JC (1989) Human monoamine oxidase A and B genes map to Xp 11.23 and are deleted in a patient with Norrie disease. Genomics 4:552–559PubMedCrossRefGoogle Scholar
  172. Lander ES, Schork NJ (1994) Genetic dissection of complex traits. Science 265:2037–2048PubMedCrossRefGoogle Scholar
  173. Langley K, Payton A, Hamshere ML, Pay HM, Lawson DC, Turic D, Ollier WER, Worthington J, Owen MJ, O’Donovan MC, Thapar A (2003) No evidence of association of two 5HT transporter gene polymorphisms and attention deficit hyperactivity disorder. Psychiatr Genet 13:107–110PubMedCrossRefGoogle Scholar
  174. Langley K, Marshall L, van den Bree M, Thomas H, Owen M, O’Donovan M, Thapar A (2004) Association of the dopamine D4 receptor gene 7-repeat allele with neuropsychological test performance of children with ADHD. Am J Psychiatry 161:133–138PubMedCrossRefGoogle Scholar
  175. Langley K, Turic D, Peirce TR, Mills S, Van Den Bree MB, Owen MJ, O’Donovan MC, Thapar A (2005) No support for association between the dopamine transporter (DAT1) gene and ADHD. Am J Med Genet B 139B:7–10CrossRefGoogle Scholar
  176. Langley K, Turic D, Rice F, Holmans P, van den Bree MB, Craddock N, Kent L, Owen MJ, O’Donovan MC, Thapar A (2008) Testing for gene × environment interaction effects in attention deficit hyperactivity disorder and associated antisocial behavior. Am J Med Genet B 147B:49–53CrossRefGoogle Scholar
  177. Lasky-Su J, Banaschewski T, Buitelaar J, Franke B, Brookes K, Sonuga-Barke E, Ebstein R, Eisenberg J, Gill M, Manor I, Miranda A, Mulas F, Oades RD, Roeyers H, Rothenberger A, Sergeant J, Steinhausen HC, Taylor E, Zhou K, Thompson M, Asherson P, Faraone SV (2007a) Partial replication of a DRD4 association in ADHD individuals using a statistically derived quantitative trait for ADHD in a family-based association test. Biol Psychiatry 62:985–990PubMedCrossRefGoogle Scholar
  178. Lasky-Su J, Biederman J, Laird N, Tsuang M, Doyle AE, Smoller JW, Lange C, Faraone SV (2007b) Evidence for an association of the dopamine D5 receptor gene on age at onset of attention deficit hyperactivity disorder. Ann Hum Genet 71:648–659PubMedCrossRefGoogle Scholar
  179. Lasky-Su J, Lange C, Biederman J, Tsuang M, Doyle AE, Smoller JW, Laird N, Faraone S (2008) Family-based association analysis of a statistically derived quantitative traits for ADHD reveal an association in DRD4 with inattentive symptoms in ADHD individuals. Am J Med Genet B 147B:100–106CrossRefGoogle Scholar
  180. Laucht M, Becker K, Schmidt MH (2006) Visual exploratory behaviour in infancy and novelty seeking in adolescence: two developmentally specific phenotypes of DRD4? J Child Psychol Psychiatry 47:1143–1151PubMedCrossRefGoogle Scholar
  181. Laucht M, Skowronek MH, Becker K, Schmidt MH, Esser G, Schulze TG, Rietschel M (2007) Interacting effects of the dopamine transporter gene and psychosocial adversity on attention-deficit/hyperactivity disorder symptoms among 15-year-olds from a high-risk community sample. Arch Gen Psychiatry 64:585–590PubMedCrossRefGoogle Scholar
  182. Laurin N, Misener VL, Crosbie J, Ickowicz A, Pathare T, Roberts W, Malone M, Tannock R, Schachar R, Kennedy JL, Barr CL (2005) Association of the calcyon gene (DRD1IP) with attention deficit/hyperactivity disorder. Mol Psychiatry 10:1117–1125PubMedCrossRefGoogle Scholar
  183. Lawson DC, Turic D, Langley K, Pay HM, Govan CF, Norton N, Hamshere ML, Owen MJ, O’Donovan MC, Thapar A (2003) Association analysis of monoamine oxidase A and attention deficit hyperactivity disorder. Am J Med Genet B 116B:84–89CrossRefGoogle Scholar
  184. Le Coniat M, Sokoloff P, Hillion J, Martres MP, Giros B, Pilon C, Schwartz JC, Berger R (1991) Chromosomal localization of the human D3 dopamine receptor gene. Hum Genet 87:618–620PubMedGoogle Scholar
  185. Lee J, Laurin N, Crosbie J, Ickowicz A, Pathare T, Malone M, Tannock R, Kennedy JL, Schachar R, Barr CL (2007) Association study of the brain-derived neurotropic factor (BDNF) gene in attention deficit hyperactivity disorder. Am J Med Genet B 144B:976–981CrossRefGoogle Scholar
  186. Lee J, Laurin N, Crosbie J, Ickowicz A, Pathare T, Malone M, Kennedy JL, Tannock R, Schachar R, Barr CL (2008) Association study of the nicotinic acetylcholine receptor alpha4 subunit gene, CHRNA4, in attention-deficit hyperactivity disorder. Genes Brain Behav 7:53–60PubMedCrossRefGoogle Scholar
  187. Lesch KP (2001) Variation of serotonergic gene expression: neurodevelopment and the complexity of response to psychopharmacologic drugs. Eur Neuropsychopharmacol 11:457–474PubMedCrossRefGoogle Scholar
  188. Lesch KP, Bengel D, Heils A, Sabol SZ, Greenberg BD, Petri S, Benjamin J, Muller CR, Hamer DH, Murphy DL (1996) Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region. Science 274:1527–1531PubMedCrossRefGoogle Scholar
  189. Levin ED (2002) Nicotinic receptor subtypes and cognitive function. J Neurobiol 53:633–640PubMedCrossRefGoogle Scholar
  190. Levy F (1991) The dopamine theory of attention deficit hyperactivity disorder (ADHD). Aust NZ J Psychiatry 25:277–283CrossRefGoogle Scholar
  191. Li S, Cullen WK, Anwyl R, Rowan MJ (2003) Dopamine-dependent facilitation of LTP induction in hippocampal CA1 by exposure to spatial novelty. Nat Neurosci 6:526–531PubMedGoogle Scholar
  192. Li J, Wang Y, Zhou R, Zhang H, Yang L, Wang B, Khan S, Faraone SV (2005) Serotonin 5-HT1B receptor gene and attention deficit hyperactivity disorder in Chinese Han subjects. Am J Med Genet B 132B:59–63CrossRefGoogle Scholar
  193. Li D, Sham PC, Owen MJ, He L (2006a) Meta-analysis shows significant association between dopamine system genes and attention deficit hyperactivity disorder (ADHD). Hum Mol Genet 15:2276–2284PubMedCrossRefGoogle Scholar
  194. Li J, Wang Y, Zhou R, Wang B, Zhang H, Yang L, Faraone SV (2006b) No association of attention-deficit/hyperactivity disorder with genes of the serotonergic pathway in Han Chinese subjects. Neurosci Lett 403:172–175PubMedCrossRefGoogle Scholar
  195. Li J, Wang Y, Zhou R, Zhang H, Yang L, Wang B, Faraone SV (2006c) Association between tryptophan hydroxylase gene polymorphisms and attention deficit hyperactivity disorder in Chinese Han population. Am J Med Genet B 141B:126–129CrossRefGoogle Scholar
  196. Li J, Zhang X, Wang Y, Zhou R, Zhang H, Yang L, Wang B, Faraone SV (2006d) The serotonin 5-HT1D receptor gene and attention-deficit hyperactivity disorder in Chinese Han subjects. Am J Med Genet B 141B:874–876CrossRefGoogle Scholar
  197. Li J, Wang Y, Zhou R, Zhang H, Yang L, Wang B, Faraone SV (2007) Association between polymorphisms in serotonin transporter gene and attention deficit hyperactivity disorder in Chinese Han subjects. Am J Med Genet B 144B:14–19CrossRefGoogle Scholar
  198. Lim MH, Kim HW, Paik KC, Cho SC, Yoon DY, Lee HJ (2006) Association of the DAT1 polymorphism with attention deficit hyperactivity disorder (ADHD): a family-based approach. Am J Med Genet B 141B:309–311CrossRefGoogle Scholar
  199. Lohmueller KE, Pearce CL, Pike M, Lander ES, Hirschhorn JN (2003) Meta-analysis of genetic association studies supports a contribution of common variants to susceptibility to common disease. Nat Genet 33:177–182PubMedCrossRefGoogle Scholar
  200. Lotrich FE, Pollock BG (2004) Meta-analysis of serotonin transporter polymorphisms and affective disorders. Psychiatr Genet 14:121–129PubMedCrossRefGoogle Scholar
  201. Lotta T, Vidgren J, Tilgmann C, Ulmanen I, Melen K, Julkunen I, Taskinen J (1995) Kinetics of human soluble and membrane-bound catechol O-methyltransferase: a revised mechanism and description of the thermolabile variant of the enzyme. Biochemistry (Mosc) 34:4202–4210CrossRefGoogle Scholar
  202. Lowe N, Kirley A, Hawi Z, Sham P, Wickham H, Kratochvil CJ, Smith SD, Lee SY, Levy F, Kent L, Middle F, Rohde LA, Roman T, Tahir E, Yazgan Y, Asherson P, Mill J, Thapar A, Payton A, Todd RD, Stephens T, Ebstein RP, Manor I, Barr CL, Wigg KG, Sinke RJ, Buitelaar JK, Smalley SL, Nelson SF, Biederman J, Faraone SV, Gill M (2004a) Joint analysis of the DRD5 marker concludes association with attention-deficit/hyperactivity disorder confined to the predominantly inattentive and combined subtypes. Am J Hum Genet 74:348–356PubMedCrossRefGoogle Scholar
  203. Lowe N, Kirley A, Mullins C, Fitzgerald M, Gill M, Hawi Z (2004b) Multiple marker analysis at the promoter region of the DRD4 gene and ADHD: evidence of linkage and association with the SNP -616. Am J Med Genet B 131B:33–37CrossRefGoogle Scholar
  204. Lunetta KL, Faraone SV, Biederman J, Laird NM (2000) Family-based tests of association and linkage that use unaffected sibs, covariates, and interactions. Am J Hum Genet 66:605–614PubMedCrossRefGoogle Scholar
  205. Lung FW, Yang P, Cheng TS, Kao WT (2006) No allele variation of the MAOA gene promoter in male Chinese subjects with attention deficit hyperactivity disorder. Neuropsychobiology 54:147–151PubMedCrossRefGoogle Scholar
  206. MacKenzie A, Quinn J (1999) A serotonin transporter gene intron 2 polymorphic region, correlated with affective disorders, has allele-dependent differential enhancer-like properties in the mouse embryo. Proc Natl Acad Sci USA 96:15251–15255PubMedCrossRefGoogle Scholar
  207. Maglott DR, Feldblyum TV, Durkin AS, Nierman WC (1996) Radiation hybrid mapping of SNAP, PCSK2, and THBD (human chromosome 20p). Mamm Genome 7:400–401PubMedCrossRefGoogle Scholar
  208. Maher BS, Marazita ML, Ferrell RE, Vanyukov MM (2002) Dopamine system genes and attention deficit hyperactivity disorder: a meta-analysis. Psychiatr Genet 12:207–215PubMedCrossRefGoogle Scholar
  209. Maisonpierre PC, Le Beau MM, Espinosa R 3rd, Ip NY, Belluscio L, de la Monte SM, Squinto S, Furth ME, Yancopoulos GD (1991) Human and rat brain-derived neurotrophic factor and neurotrophin-3: gene structures, distributions, and chromosomal localizations. Genomics 10:558–568PubMedCrossRefGoogle Scholar
  210. Malleret G, Hen R, Guillou JL, Segu L, Buhot MC (1999) 5-HT1B receptor knock-out mice exhibit increased exploratory activity and enhanced spatial memory performance in the Morris water maze. J Neurosci 19:6157–6168PubMedGoogle Scholar
  211. Manor I, Kotler M, Sever Y, Eisenberg J, Cohen H, Ebstein RP, Tyano S (2000) Failure to replicate an association between the catechol-O-methyltransferase polymorphism and attention deficit hyperactivity disorder in a second, independently recruited Israeli cohort. Am J Med Genet 96:858–860PubMedCrossRefGoogle Scholar
  212. Manor I, Eisenberg J, Tyano S, Sever Y, Cohen H, Ebstein RP, Kotler M (2001) Family-based association study of the serotonin transporter promoter region polymorphism (5-HTTLPR) in attention deficit hyperactivity disorder. Am J Med Genet B 105B:91–95Google Scholar
  213. Manor I, Tyano S, Eisenberg J, Bachner-Melman R, Kotler M, Ebstein RP (2002a) The short DRD4 repeats confer risk to attention deficit hyperactivity disorder in a family-based design and impair performance on a continuous performance test (TOVA). Mol Psychiatry 7:790–794PubMedCrossRefGoogle Scholar
  214. Manor I, Tyano S, Mel E, Eisenberg J, Bachner-Melman R, Kotler M, Ebstein RP (2002b) Family-based and association studies of monoamine oxidase A and attention deficit hyperactivity disorder (ADHD): preferential transmission of the long promoter-region repeat and its association with impaired performance on a continuous performance test (TOVA). Mol Psychiatry 7:626–632PubMedCrossRefGoogle Scholar
  215. Manor I, Corbex M, Eisenberg J, Gritsenkso I, Bachner-Melman R, Tyano S, Ebstein RP (2004) Association of the dopamine D5 receptor with attention deficit hyperactivity disorder (ADHD) and scores on a continuous performance test (TOVA). Am J Med Genet B 127B:73–77CrossRefGoogle Scholar
  216. Manuck SB, Flory JD, Ferrell RE, Mann JJ, Muldoon MF (2000) A regulatory polymorphism of the monoamine oxidase-A gene may be associated with variability in aggression, impulsivity, and central nervous system serotonergic responsivity. Psychiatry Res 95:9–23PubMedCrossRefGoogle Scholar
  217. Martin P, Waters N, Schmidt CJ, Carlsson A, Carlsson ML (1998) Rodent data and general hypothesis: antipsychotic action exerted through 5-Ht2A receptor antagonism is dependent on increased serotonergic tone. J Neural Transm 105:365–396PubMedCrossRefGoogle Scholar
  218. Mattson MP (2008) Glutamate and neurotrophic factors in neuronal plasticity and disease. Ann N Y Acad Sci 1144:97–112PubMedGoogle Scholar
  219. McCracken JT, Smalley SL, McGough JJ, Crawford L, Del’Homme M, Cantor RM, Liu A, Nelson SF (2000) Evidence for linkage of a tandem duplication polymorphism upstream of the dopamine D4 receptor gene (DRD4) with attention deficit hyperactivity disorder (ADHD). Mol Psychiatry 5:531–536PubMedCrossRefGoogle Scholar
  220. McEvoy B, Hawi Z, Fitzgerald M, Gill M (2002) No evidence of linkage or association between the norepinephrine transporter (NET) gene polymorphisms and ADHD in the Irish population. Am J Med Genet 114:665–666PubMedCrossRefGoogle Scholar
  221. Meyer-Lindenberg A, Buckholtz JW, Kolachana B, RH A, Pezawas L, Blasi G, Wabnitz A, Honea R, Verchinski B, Callicott JH, Egan M, Mattay V, Weinberger DR (2006) Neural mechanisms of genetic risk for impulsivity and violence in humans. Proc Natl Acad Sci USA 103:6269–6274PubMedCrossRefGoogle Scholar
  222. Michelson D, Allen AJ, Busner J, Casat C, Dunn D, Kratochvil C, Newcorn J, Sallee FR, Sangal RB, Saylor K, West S, Kelsey D, Wernicke J, Trapp NJ, Harder D (2002) Once-daily atomoxetine treatment for children and adolescents with attention deficit hyperactivity disorder: a randomized, placebo-controlled study. Am J Psychiatry 159:1896–1901PubMedCrossRefGoogle Scholar
  223. Mill J, Curran S, Kent L, Richards S, Gould A, Virdee V, Huckett L, Sharp J, Batten C, Fernando S, Simanoff E, Thompson M, Zhao J, Sham P, Taylor E, Asherson P (2001) attention deficit hyperactivity disorder (ADHD) and the dopamine D4 receptor gene: evidence of association but no linkage in a UK sample. Mol Psychiatry 6:440–444PubMedCrossRefGoogle Scholar
  224. Mill J, Asherson P, Browes C, D’Souza U, Craig I (2002) Expression of the dopamine transporter gene is regulated by the 3′ UTR VNTR: Evidence from brain and lymphocytes using quantitative RT-PCR. Am J Med Genet 114:975–979PubMedCrossRefGoogle Scholar
  225. Mill J, Curran S, Richards S, Taylor E, Asherson P (2004a) Polymorphisms in the dopamine D5 receptor (DRD5) gene and ADHD. Am J Med Genet B 125B:38–42CrossRefGoogle Scholar
  226. Mill J, Richards S, Knight J, Curran S, Taylor E, Asherson P (2004b) Haplotype analysis of SNAP-25 suggests a role in the aetiology of ADHD. Mol Psychiatry 9:801–810PubMedCrossRefGoogle Scholar
  227. Mill J, Xu X, Ronald A, Curran S, Price T, Knight J, Craig I, Sham P, Plomin R, Asherson P (2005) Quantitative trait locus analysis of candidate gene alleles associated with attention deficit hyperactivity disorder (ADHD) in five genes: DRD4, DAT1, DRD5, SNAP-25, and 5HT1B. Am J Med Genet B 133B:68–73CrossRefGoogle Scholar
  228. Misener VL, Luca P, Azeke O, Crosbie J, Waldman I, Tannock R, Roberts W, Malone M, Schachar R, Ickowicz A, Kennedy JL, Barr CL (2004) Linkage of the dopamine receptor D1 gene to attention-deficit/hyperactivity disorder. Mol Psychiatry 9:500–509PubMedCrossRefGoogle Scholar
  229. Munafo MR, Clark T, Flint J (2005) Does measurement instrument moderate the association between the serotonin transporter gene and anxiety-related personality traits? A meta-analysis. Mol Psychiatry 10:415–419PubMedCrossRefGoogle Scholar
  230. Murphy DL, Andrews AM, Wichems CH, Li Q, Tohda M, Greenberg B (1998) Brain serotonin neurotransmission: an overview and update with an emphasis on serotonin subsystem heterogeneity, multiple receptors, interactions with other neurotransmitter systems, and consequent implications for understanding the actions of serotonergic drugs. J Clin Psychiatry 59(Suppl 15):4–12PubMedGoogle Scholar
  231. Neuman RJ, Lobos E, Reich W, Henderson CA, Sun LW, Todd RD (2007) Prenatal smoking exposure and dopaminergic genotypes interact to cause a severe ADHD subtype. Biol Psychiatry 61:1320–1328PubMedCrossRefGoogle Scholar
  232. Neville MJ, Johnstone EC, Walton RT (2004) Identification and characterization of ANKK1: a novel kinase gene closely linked to DRD2 on chromosome band 11q23.1. Hum Mutat 23:540–545PubMedCrossRefGoogle Scholar
  233. Nicodemus KK (2008) Catmap: case-control and TDT meta-analysis package. BMC Bioinf 9:130CrossRefGoogle Scholar
  234. Noain D, Avale ME, Wedemeyer C, Calvo D, Peper M, Rubinstein M (2006) Identification of brain neurons expressing the dopamine D4 receptor gene using BAC transgenic mice. Eur J NeuroSci 24:2429–2438PubMedCrossRefGoogle Scholar
  235. Noble EP, Blum K, Ritchie T, Montgomery A, Sheridan PJ (1991) Allelic association of the D2 dopamine receptor gene with receptor-binding characteristics in alcoholism. Arch Gen Psychiatry 48:648–654PubMedGoogle Scholar
  236. Norton N, Owen MJ (2005) HTR2A: association and expression studies in neuropsychiatric genetics. Ann Med 37:121–129PubMedCrossRefGoogle Scholar
  237. O’Neill MF, Heron-Maxwell CL, Shaw G (1999) 5-HT2 receptor antagonism reduces hyperactivity induced by amphetamine, cocaine, and MK-801 but not D1 agonist C-APB. Pharmacol Biochem Behav 63:237–243PubMedCrossRefGoogle Scholar
  238. Ogdie MN, Macphie IL, Minassian SL, Yang M, Fisher SE, Francks C, Cantor RM, McCracken JT, McGough JJ, Nelson SF, Monaco AP, Smalley SL (2003) A genomewide scan for attention-deficit/hyperactivity disorder in an extended sample: suggestive linkage on 17p11. Am J Hum Genet 72:1268–1279PubMedCrossRefGoogle Scholar
  239. Okuyama Y, Ishiguro H, Toru M, Arinami T (1999) A genetic polymorphism in the promoter region of DRD4 associated with expression and schizophrenia. Biochem Biophys Res Commun 258:292–295PubMedCrossRefGoogle Scholar
  240. Oldenhof J, Vickery R, Anafi M, Oak J, Ray A, Schoots O, Pawson T, von Zastrow M, Van Tol HH (1998) SH3 binding domains in the dopamine D4 receptor. Biochemistry (Mosc) 37:15726–15736CrossRefGoogle Scholar
  241. Oquendo MA, Hastings RS, Huang Y-Y, Simpson N, Ogden RT, Hu X-Z, Goldman D, Arango V, Van Heertum RL, Mann JJ, Parsey RV (2007) Brain Serotonin Transporter Binding in Depressed Patients With Bipolar Disorder Using Positron Emission Tomography. Arch Gen Psychiatry 64:201–208PubMedCrossRefGoogle Scholar
  242. Oswald P, Souery D, Mendlewicz J (2004) Molecular genetics of affective disorders. Prog Neuropsychopharmacol Biol Psychiatry 28:865–877PubMedCrossRefGoogle Scholar
  243. Ozaki N, Rosenthal NE, Pesonen U, Lappalainen J, Feldman-Naim S, Schwartz PJ, Turner EH, Goldman D (1996) Two naturally occurring amino acid substitutions of the 5-HT2A receptor: similar prevalence in patients with seasonal affective disorder and controls. Biol Psychiatry 40:1267–1272PubMedCrossRefGoogle Scholar
  244. Pacholczyk T, Blakely RD, Amara S (1991) Expression cloning of a cocaine- and antidepressant-sensitive noradrenaline transporter. Nature 350:350–354PubMedCrossRefGoogle Scholar
  245. Park L, Nigg JT, Waldman ID, Nummy KA, Huang-Pollock C, Rappley M, Friderici KH (2005) Association and linkage of alpha-2A adrenergic receptor gene polymorphisms with childhood ADHD. Mol Psychiatry 10:572–580PubMedCrossRefGoogle Scholar
  246. Payton A, Holmes J, Barrett JH, Hever T, Fitzpatrick H, Trumper AL, Harrington R, McGuffin P, O’Donovan M, Owen M, Ollier W, Worthington J, Thapar A (2001) Examining for association between candidate gene polymorphisms in the dopamine pathway and attention-deficit hyperactivity disorder: a family-based study. Am J Med Genet 105:464–470PubMedCrossRefGoogle Scholar
  247. Pennington BF, Ozonoff S (1996) Executive functions and developmental psychopathology. J Child Psychol Psychiatry 37:51–87PubMedCrossRefGoogle Scholar
  248. Petronis A, Van Tol HH, Lichter JB, Livak KJ, Kennedy JL (1993) The D4 dopamine receptor gene maps on 11p proximal to HRAS. Genomics 18:161–163PubMedCrossRefGoogle Scholar
  249. Pliszka SR, McCracken JT, Maas JW (1996) Catecholamines in attention-deficit hyperactivity disorder: current perspectives. J Am Acad Child Adolesc Psychiatry 35:264–272PubMedCrossRefGoogle Scholar
  250. Ponce G, Hoenicka J, Rodriguez-Jimenez R, Gozalo A, Jimenez M, Monasor R, Aragues M, Rubio G, Jimenez-Arriero MA, Ramos JA, Palomo T (2004) IDRD2 TaqIA polymorphism is associated with urinary homovanillic acid levels in a sample of Spanish male alcoholic patients. Neurotox Res 6:373–377PubMedCrossRefGoogle Scholar
  251. Qian Q, Wang Y, Zhou R, Li J, Wang B, Glatt S, Faraone SV (2003) Family-based and case-control association studies of catechol-O-methyltransferase in attention deficit hyperactivity disorder suggest genetic sexual dimorphism. Am J Med Genet B 118B:103–109CrossRefGoogle Scholar
  252. Qian Q, Wang Y, Zhou R, Yang L, Faraone SV (2004) Family-based and case-control association studies of DRD4 and DAT1 polymorphisms in Chinese attention deficit hyperactivity disorder patients suggest long repeats contribute to genetic risk for the disorder. Am J Med Genet B 128B:84–89CrossRefGoogle Scholar
  253. Quist JF, Barr CL, Schachar R, Roberts W, Malone M, Tannock R, Basile VS, Beitchman J, Kennedy JL (2000) Evidence for the serotonin HTR2A receptor gene as a susceptibility factor in attention deficit hyperactivity disorder (ADHD). Mol Psychiatry 5:537–541PubMedCrossRefGoogle Scholar
  254. Renner TJ, Walitza S, Dempfle A, Eckert L, Romanos M, Gerlach M, Schafer H, Warnke A, Lesch KP, Jacob C (2008) Allelic variants of SNAP25 in a family-based sample of ADHD. J Neural Transm 115:317–321PubMedCrossRefGoogle Scholar
  255. Ribases M, Ramos-Quiroga JA, Hervas A, Bosch R, Bielsa A, Gastaminza X, Artigas J, Rodriguez-Ben S, Estivill X, Casas M, Cormand B, Bayes M (2009) Exploration of 19 serotoninergic candidate genes in adults and children with attention-deficit/hyperactivity disorder identifies association for 5HT2A, DDC and MAOB. Mol Psychiatry 14:71–85PubMedCrossRefGoogle Scholar
  256. Risch NJ (2000) Searching for genetic determinants in the new millennium. Nature 405:847–856PubMedCrossRefGoogle Scholar
  257. Risch N, Merikangas K (1996) The future of genetic studies of complex human diseases. Science 273:1516–1517PubMedCrossRefGoogle Scholar
  258. Ritz M, Lamb R, Goldberg S, Kuhar M (1987) Cocaine receptors on dopamine transporters are related to self-administration of cocaine. Science 237:1219–1223PubMedCrossRefGoogle Scholar
  259. Rogeness GA, Hernandez JM, Macedo CA, Mitchell EL (1982) Biochemical differences in children with conduct disorder socialized and undersocialized. Am J Psychiatry 139:307–311PubMedGoogle Scholar
  260. Rogeness GA, Crawford L, McNamara A (1989) Plasma dopamine-beta-hydroxylase and preschool behavior in children with conduct disorder. Child Psychiatry Hum Dev 20:149–156PubMedCrossRefGoogle Scholar
  261. Roman T, Schmitz M, Polanczyk G, Eizirik M, Rohde LA, Hutz MH (2001) Attention-deficit hyperactivity disorder: a study of association with both the dopamine transporter gene and the dopamine D4 receptor gene. Am J Med Genet 105:471–478PubMedCrossRefGoogle Scholar
  262. Roman T, Schmitz M, Polanczyk GV, Eizirik M, Rohde LA, Hutz MH (2002) Further evidence for the association between attention-deficit/hyperactivity disorder and the dopamine-beta-hydroxylase gene. Am J Med Genet 114:154–158PubMedCrossRefGoogle Scholar
  263. Roman T, Schmitz M, Polanczyk GV, Eizirik M, Rohde LA, Hutz MH (2003) Is the alpha-2A adrenergic receptor gene (ADRA2A) associated with attention-deficit/hyperactivity disorder? Am J Med Genet B 120B:116–120CrossRefGoogle Scholar
  264. Rowe D, Stever C, Giedinghagen L, Gard J, Cleveland H, Terris S, Mohr J, Sherman S, Abramowitz A, Waldman I (1998) Dopamine DRD4 receptor polymorphism and attention deficit hyperactivity disorder. Mol Psychiatry 3:419–426PubMedCrossRefGoogle Scholar
  265. Rowe DC, Van den Oord EJ, Stever C, Giedinghagen LN, Gard JM, Cleveland HH, Gilson M, Terris ST, Mohr JH, Sherman S, Abramowitz A, Waldman ID (1999) Dopamine D2 receptor gene variants: association and linkage studies in impulsive-addictive-compulsive behaviour. Mol Psychiatry 4:580–586PubMedCrossRefGoogle Scholar
  266. Roy A, Linnoila M (1988) Suicidal behavior, impulsiveness and serotonin. Acta Psychiatr Scand 78:529–535PubMedCrossRefGoogle Scholar
  267. Rubinstein M, Phillips TJ, Bunzow JR, Falzone TL, Dziewczapolski G, Zhang G, Fang Y, Larson JL, McDougall JA, Chester JA, Saez C, Pugsley TA, Gershanik O, Low MJ, Grandy DK (1997) Mice lacking dopamine D4 receptors are supersensitive to ethanol, cocaine, and methamphetamine. Cell 90:991–1001PubMedCrossRefGoogle Scholar
  268. Sabol SZ, Hu S, Hamer D (1998) A functional polymorphism in the monoamine oxidase A gene promoter. Hum Genet 103:273–279PubMedCrossRefGoogle Scholar
  269. Saudou F, Amara DA, Dierich A, LeMeur M, Ramboz S, Segu L, Buhot MC, Hen R (1994) Enhanced aggressive behavior in mice lacking 5-HT1B receptor. Science 265:1875–1878PubMedCrossRefGoogle Scholar
  270. Scanlon PD, Raymond FA, Weinshilboum RM (1979) Catechol-O-methyltransferase: thermolabile enzyme in erythrocytes of subjects homozygous for allele for low activity. Science 203:63–65PubMedCrossRefGoogle Scholar
  271. Schimmelmann BG, Friedel S, Dempfle A, Warnke A, Lesch KP, Walitza S, Renner TJ, Romanos M, Herpertz-Dahlmann B, Linder M, Schafer H, Seitz C, Palmason H, Freitag C, Meyer J, Konrad K, Hinney A, Hebebrand J (2007) No evidence for preferential transmission of common valine allele of the Val66Met polymorphism of the brain-derived neurotrophic factor gene (BDNF) in ADHD. J Neural Transm 114:523–526PubMedCrossRefGoogle Scholar
  272. Schinka JA, Busch RM, Robichaux-Keene N (2004) A meta-analysis of the association between the serotonin transporter gene polymorphism (5-HTTLPR) and trait anxiety. Mol Psychiatry 9:235–238CrossRefGoogle Scholar
  273. Schmidt L, Fox N, Perez-Edgar K, Hu S, Hamer D (2001) Association of DRD4 with attention problems in normal childhood development. Psychiatr Genet 11:25–29PubMedCrossRefGoogle Scholar
  274. Schmitz M, Denardin D, Silva TL, Pianca T, Roman T, Hutz MH, Faraone SV, Rohde LA (2006) Association between alpha-2A-adrenergic receptor gene and ADHD inattentive type. Biol Psychiatry 60:1028–1033PubMedCrossRefGoogle Scholar
  275. Schulz KP, Fan J, Tang CY, Newcorn JH, Buchsbaum MS, Cheung AM, Halperin JM (2004) Response inhibition in adolescents diagnosed with attention deficit hyperactivity disorder during childhood: an event-related FMRI study. Am J Psychiatry 161:1650–1657PubMedCrossRefGoogle Scholar
  276. Seaman MI, Fisher JB, Chang F, Kidd KK (1999) Tandem duplication polymorphism upstream of the dopamine D4 receptor gene (DRD4). Am J Med Genet 88:705–709PubMedCrossRefGoogle Scholar
  277. Seeger G, Schloss P, Schmidt MH (2001) Functional polymorphism within the promoter of the serotonin transporter gene is associated with severe hyperkinetic disorders. Mol Psychiatry 6:235–238PubMedCrossRefGoogle Scholar
  278. Sen S, Villafuerte S, Nesse R, Stoltenberg SF, Hopcian J, Gleiberman L, Weder A, Burmeister M (2004) Serotonin transporter and GABA(A) Alpha 6 receptor variants are associated with neuroticism. Biol Psychiatry 55:244–249PubMedCrossRefGoogle Scholar
  279. Sery O, Drtilkova I, Theiner P, Pitelova R, Staif R, Znojil V, Lochman J, Didden W (2006) Polymorphism of DRD2 gene and ADHD. Neuroendocrinol Lett 27:236–240PubMedGoogle Scholar
  280. Sheehan K, Lowe N, Kirley A, Mullins C, Fitzgerald M, Gill M, Hawi Z (2005) Tryptophan hydroxylase 2 (TPH2) gene variants associated with ADHD. Mol Psychiatry 10:944–949PubMedCrossRefGoogle Scholar
  281. Sheehan K, Hawi Z, Gill M, Kent L (2007) No association between TPH2 gene polymorphisms and ADHD in a UK sample. Neurosci Lett 412:105–107PubMedCrossRefGoogle Scholar
  282. Sherrington R, Mankoo B, Attwood J, Kalsi G, Curtis D, Buetow K, Povey S, Gurling H (1993) Cloning of the human dopamine D5 receptor gene and identification of a highly polymorphic microsatellite for the DRD5 locus that shows tight linkage to the chromosome 4p reference marker RAF1P1. Genomics 18:423–425PubMedCrossRefGoogle Scholar
  283. Simsek M, Al-Sharbati M, Al-Adawi S, Ganguly SS, Lawatia K (2005) Association of the risk allele of dopamine transporter gene (DAT1*10) in Omani male children with attention-deficit hyperactivity disorder. Clin Biochem 38:739–742PubMedCrossRefGoogle Scholar
  284. Smith KM, Daly M, Fischer M, Yiannoutsos CT, Bauer L, Barkley R, Navia BA (2003) Association of the dopamine beta hydroxylase gene with attention deficit hyperactivity disorder: genetic analysis of the Milwaukee longitudinal study. Am J Med Genet B 119B:77–85CrossRefGoogle Scholar
  285. Smoller JW, Biederman J, Arbeitman L, Doyle AE, Fagerness J, Perlis RH, Sklar P, Faraone SV (2006) Association between the 5HT1B receptor gene (HTR1B) and the inattentive subtype of ADHD. Biol Psychiatry 59:460–467PubMedCrossRefGoogle Scholar
  286. Solanto MV (1998) Neuropsychopharmacological mechanisms of stimulant drug action in attention-deficit hyperactivity disorder: a review and integration. Behav Brain Res 94:127–152PubMedCrossRefGoogle Scholar
  287. Sollner T, Whiteheart SW, Brunner M, Erdjument-Bromage H, Geromanos S, Tempst P, Rothman JE (1993) SNAP receptors implicated in vesicle targeting and fusion. Nature 362:318–324PubMedCrossRefGoogle Scholar
  288. Sparkes RS, Lan N, Klisak I, Mohandas T, Diep A, Kojis T, Heinzmann C, Shih JC (1991) Assignment of a serotonin 5HT-2 receptor gene (HTR2) to human chromosome 13q14-q21 and mouse chromosome 14. Genomics 9:461–465PubMedCrossRefGoogle Scholar
  289. Spencer T, Heiligenstein JH, Biederman J, Faries DE, Kratochvil CJ, Conners CK, Potter WZ (2002) Results from 2 proof-of-concept, placebo-controlled studies of atomoxetine in children with attention-deficit/hyperactivity disorder. J Clin Psychiatry 63:1140–1147PubMedGoogle Scholar
  290. Spivak B, Vered Y, Yoran-Hegesh R, Averbuch E, Mester R, Graf E, Weizman A (1999) Circulatory levels of catecholamines, serotonin and lipids in attention deficit hyperactivity disorder. Acta Psychiatr Scand 99:300–304PubMedCrossRefGoogle Scholar
  291. Stahl SM (2003) Neurotransmission of cognition, part 3. Mechanism of action of selective NRIs: both dopamine and norepinephrine increase in prefrontal cortex. J Clin Psychiatry 64:230–231PubMedGoogle Scholar
  292. Stein DJ, Hollander E, Liebowitz MR (1993) Neurobiology of impulsivity and the impulse control disorders. J Neuropsychiatry Clin Neurosci 5:9–17PubMedGoogle Scholar
  293. Steinlein OK, Mulley JC, Propping P, Wallace RH, Phillips HA, Sutherland GR, Scheffer IE, Berkovic SF (1995) A missense mutation in the neuronal nicotinic acetylcholine receptor alpha 4 subunit is associated with autosomal dominant nocturnal frontal lobe epilepsy. Nat Genet 11:201–203PubMedCrossRefGoogle Scholar
  294. Stevenson J, Langley K, Pay H, Payton A, Worthington J, Ollier W, Thapar A, Stevenson J, Langley K, Pay H, Payton A, Worthington J, Ollier W, Thapar A (2005) attention deficit hyperactivity disorder with reading disabilities: preliminary genetic findings on the involvement of the ADRA2A gene. J Child Psychol Psychiatry 46:1081–1088PubMedCrossRefGoogle Scholar
  295. Sunahara RK, Guan HC, O’Dowd BF, Seeman P, Laurier LG, Ng G, George SR, Torchia J, Van Tol HH, Niznik HB (1991) Cloning of the gene for a human dopamine D5 receptor with higher affinity for dopamine than D1. Nature 350:614–619PubMedCrossRefGoogle Scholar
  296. Sunohara GA, Roberts W, Malone M, Schachar RJ, Tannock R, Basile VS, Wigal T, Wigal SB, Schuck S, Moriarty J, Swanson JM, Kennedy JL, Barr CL (2000) Linkage of the dopamine D4 receptor gene and attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry 39:1537–1542PubMedCrossRefGoogle Scholar
  297. Swanson JM, Sunohara GA, Kennedy JL, Regino R, Fineberg E, Wigal T, Lerner M, Williams L, LaHoste GJ, Wigal S (1998) Association of the dopamine receptor D4 (DRD4) gene with a refined phenotype of attention deficit hyperactivity disorder (ADHD): a family-based approach. Mol Psychiatry 3:38–41PubMedCrossRefGoogle Scholar
  298. Swanson J, Oosterlaan J, Murias M, Schuck S, Flodman P, Spence MA, Wasdell M, Ding Y, Chi HC, Smith M, Mann M, Carlson C, Kennedy JL, Sergeant JA, Leung P, Zhang YP, Sadeh A, Chen C, Whalen CK, Babb KA, Moyzis R, Posner MI (2000a) Attention deficit/hyperactivity disorder children with a 7-repeat allele of the dopamine receptor D4 gene have extreme behavior but normal performance on critical neuropsychological tests of attention. Proc Natl Acad Sci USA 97:4754–4759PubMedCrossRefGoogle Scholar
  299. Swanson JM, Flodman P, Kennedy J, Spence MA, Moyzis R, Schuck S, Murias M, Moriarity J, Barr C, Smith M, Posner M (2000b) Dopamine genes and ADHD. Neurosci Biobehav Rev 24:21–25PubMedCrossRefGoogle Scholar
  300. Taerk E, Grizenko N, Ben Amor L, Lageix P, Mbekou V, Deguzman R, Torkaman-Zehi A, Ter Stepanian M, Baron C, Joober R (2004) Catechol-O-methyltransferase (COMT) Val108/158 Met polymorphism does not modulate executive function in children with ADHD. BMC Med Genet 5:30PubMedCrossRefGoogle Scholar
  301. Tahir E, Curran S, Yazgan Y, Ozbay F, Cirakoglu B, Asherson PJ (2000a) No association between low- and high-activity catecholamine-methyl-transferase (COMT) and attention deficit hyperactivity disorder (ADHD) in a sample of Turkish children. Am J Med Genet 96:285–288PubMedCrossRefGoogle Scholar
  302. Tahir E, Yazgan Y, Cirakoglu B, Ozbay F, Waldman I, Asherson PJ (2000b) Association and linkage of DRD4 and DRD5 with attention deficit hyperactivity disorder (ADHD) in a sample of Turkish children. Mol Psychiatry 5:396–404PubMedCrossRefGoogle Scholar
  303. Tang G, Ren D, Xin R, Qian Y, Wang D, Jiang S (2001) Lack of association between the tryptophan hydroxylase gene A218C polymorphism and attention-deficit hyperactivity disorder in Chinese Han population. Am J Med Genet 105:485–488PubMedCrossRefGoogle Scholar
  304. Thompson J, Thomas N, Singleton A, Piggott M, Lloyd S, Perry EK, Morris CM, Perry RH, Ferrier IN, Court JA (1997) D2 dopamine receptor gene (DRD2) Taq1 A polymorphism: reduced dopamine D2 receptor binding in the human striatum associated with the A1 allele. Pharmacogenetics 7:479–484PubMedCrossRefGoogle Scholar
  305. Todd RD, Jong YJ, Lobos EA, Reich W, Heath AC, Neuman RJ (2001a) No association of the dopamine transporter gene 3′ VNTR polymorphism with ADHD subtypes in a population sample of twins. Am J Med Genet 105:745–748PubMedCrossRefGoogle Scholar
  306. Todd RD, Neuman RJ, Lobos EA, Jong YJ, Reich W, Heath AC (2001b) Lack of association of dopamine D4 receptor gene polymorphisms with ADHD subtypes in a population sample of twins. Am J Med Genet 105:432–438PubMedCrossRefGoogle Scholar
  307. Todd RD, Lobos EA, Sun LW, Neuman RJ (2003) Mutational analysis of the nicotinic acetylcholine receptor alpha 4 subunit gene in attention deficit/hyperactivity disorder: evidence for association of an intronic polymorphism with attention problems. Mol Psychiatry 8:103–108PubMedCrossRefGoogle Scholar
  308. Tsai SJ (2003) Attention-deficit hyperactivity disorder and brain-derived neurotrophic factor: a speculative hypothesis. Med Hypotheses 60:849–851PubMedCrossRefGoogle Scholar
  309. Turic D, Williams H, Langley K, Owen M, Thapar A, O’Donovan MC (2005) A family based study of catechol-O-methyltransferase (COMT) and attention deficit hyperactivity disorder (ADHD). Am J Med Genet B 133B:64–67CrossRefGoogle Scholar
  310. Usiello A, Baik JH, Rouge-Pont F, Picetti R, Dierich A, LeMeur M, Piazza PV, Borrelli E (2000) Distinct functions of the two isoforms of dopamine D2 receptors. Nature 408:199–203PubMedCrossRefGoogle Scholar
  311. Vallone D, Picetti R, Borrelli E (2000) Structure and function of dopamine receptors. Neurosci Biobehav Rev 24:125–132PubMedCrossRefGoogle Scholar
  312. Van Tol HH, Wu CM, Guan HC, Ohara K, Bunzow JR, Civelli O, Kennedy J, Seeman P, Niznik HB, Jovanovic V (1992) Multiple dopamine D4 receptor variants in the human population. Nature 358:149–152PubMedCrossRefGoogle Scholar
  313. Vandenbergh DJ, Persico AM, Hawkins AL, Griffin CA, Li X, Jabs EW, Uhl GR (1992) Human dopamine transporter gene (DAT1) maps to chromosome 5p15.3 and displays a VNTR. Genomics 14:1104–1106PubMedCrossRefGoogle Scholar
  314. Volkow N, Ding Y, Fowler J, Wang G, Logan J, Gatley J et al (1995) Is methylphenidate like cocaine? Arch Gen Psychiatry 52:456–463PubMedGoogle Scholar
  315. Waldman ID (2005) Statistical approaches to complex phenotypes: evaluating neuropsychological endophenotypes for attention-deficit/hyperactivity disorder. Biol Psychiatry 57:1347–1356PubMedCrossRefGoogle Scholar
  316. Waldman I, Gizer I (2006) The genetics of attention deficit hyperactivity disorder. Clin Psychol Rev 26:396–432PubMedCrossRefGoogle Scholar
  317. Waldman I, Rhee S (2002) Behavioral and molecular genetic studies. In: Sandberg S (ed) Hyperactivity and Attention Disorders of childhood, 2nd edn. Wiley, New York, pp 290–335Google Scholar
  318. Waldman I, Rowe D, Abramowitz A, Kozel S, Mohr J, Sherman S, Cleveland H, Sanders M, Gard J, Stever C (1998) Association and linkage of the dopamine transporter gene and attention-deficit hyperactivity disorder in children: heterogeneity owing to diagnostic subtype and severity. Am J Hum Genet 63:1767–1776PubMedCrossRefGoogle Scholar
  319. Waldman ID, Nigg JT, Gizer IR, Park L, Rappley MD, Friderici K (2006) The adrenergic receptor alpha-2A gene (ADRA2A) and neuropsychological executive functions as putative endophenotypes for childhood ADHD. Cogn Affect Behav Neurosci 6:18–30PubMedCrossRefGoogle Scholar
  320. Walitza S, Renner TJ, 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 KP (2005) Transmission disequilibrium of polymorphic variants in the tryptophan hydroxylase-2 gene in attention-deficit/hyperactivity disorder. Mol Psychiatry 10:1126–1132PubMedCrossRefGoogle Scholar
  321. Walther DJ, Peter JU, Bashammakh S, Hortnagl H, Voits M, Fink H, Bader M (2003) Synthesis of serotonin by a second tryptophan hydroxylase isoform. Science 299:76PubMedCrossRefGoogle Scholar
  322. Wang B, Wang Y, Zhou R, Li J, Qian Q, Yang L, Guan L, Faraone SV (2006) Possible association of the alpha-2A adrenergic receptor gene (ADRA2A) with symptoms of attention-deficit/hyperactivity disorder. Am J Med Genet B 141:130–134CrossRefGoogle Scholar
  323. Wang Y, Wang Z, Yao K, Tanaka K, Yang Y, Shirakawa O, Maeda K (2008) Lack of association between the dopamine transporter gene 3′ VNTR polymorphism and attention deficit hyperactivity disorder in Chinese Han children: case-control and family-based studies. Kobe J Med Sci 53:327–333PubMedGoogle Scholar
  324. Warren JT Jr, Peacock ML, Fink JK (1992) An RsaI polymorphism in the human serotonin receptor gene (HTR1A): detection by DGGE and RFLP analysis. Hum Mol Genet 1:778PubMedCrossRefGoogle Scholar
  325. Weinshilboum R, Dunnette J (1981) Thermal stability and the biochemical genetics of erythrocyte catechol-O-methyl-transferase and plasma dopamine-beta-hydroxylase. Clin Genet 19:426–437PubMedCrossRefGoogle Scholar
  326. Weiss S, Nosten-Bertrand M, McIntosh JM, Giros B, Martres MP (2007a) Nicotine improves cognitive deficits of dopamine transporter knockout mice without long-term tolerance. Neuropsychopharmacology 32:2465–2478PubMedCrossRefGoogle Scholar
  327. Weiss S, Tzavara ET, Davis RJ, Nomikos GG, Michael McIntosh J, Giros B, Martres MP (2007b) Functional alterations of nicotinic neurotransmission in dopamine transporter knock-out mice. Neuropharmacology 52:1496–1508PubMedCrossRefGoogle Scholar
  328. Wigg K, Zai G, Schachar R, Tannock R, Roberts W, Malone M, Kennedy JL, Barr CL (2002) attention deficit hyperactivity disorder and the gene for dopamine Beta-hydroxylase. Am J Psychiatry 159:1046–1048PubMedCrossRefGoogle Scholar
  329. Wigg KG, Takhar A, Ickowicz A, Tannock R, Kennedy JL, Pathare T, Malone M, Schachar R, Barr CL (2006) Gene for the serotonin transporter and ADHD. No association with two functional polymorphisms. Am J Med Genet B 141B:566–570CrossRefGoogle Scholar
  330. Wilens TE, Verlinden MH, Adler LA, Wozniak PJ, West SA (2006) ABT-089, a neuronal nicotinic receptor partial agonist, for the treatment of attention-deficit/hyperactivity disorder in adults: results of a pilot study. Biol Psychiatry 59:1065–1070PubMedCrossRefGoogle Scholar
  331. Willcutt EG, Doyle AE, Nigg JT, Faraone SV, Pennington BF (2005) Validity of the executive function theory of attention-deficit/hyperactivity disorder: a meta-analytic review. Biol Psychiatry 57:1336–1346PubMedCrossRefGoogle Scholar
  332. Xu C, Schachar R, Tannock R, Roberts W, Malone M, Kennedy JL, Barr CL (2001) Linkage study of the alpha2A adrenergic receptor in attention-deficit hyperactivity disorder families. Am J Med Genet 105:159–162PubMedCrossRefGoogle Scholar
  333. Xu X, Knight J, Brookes K, Mill J, Sham P, Craig I, Taylor E, Asherson P (2005a) DNA pooling analysis of 21 norepinephrine transporter gene SNPs with attention deficit hyperactivity disorder: no evidence for association. Am J Med Genet B 134:115–118CrossRefGoogle Scholar
  334. Xu X, Mill J, Chen CK, Brookes K, Taylor E, Asherson P (2005b) Family-based association study of serotonin transporter gene polymorphisms in attention deficit hyperactivity disorder No evidence for association in UK and Taiwanese samples. Am J Med Genet B 139B:11–13CrossRefGoogle Scholar
  335. Xu X, Rakovski C, Xiping X, Laird N (2006) An efficient family-based association test using multiple markers. Genet Epidemiol 30:620–626PubMedCrossRefGoogle Scholar
  336. Xu X, Brookes K, Chen CK, Huang YS, Wu YY, Asherson P (2007a) Association study between the monoamine oxidase A gene and attention deficit hyperactivity disorder in Taiwanese samples. BMC Psychiatry 7:10PubMedCrossRefGoogle Scholar
  337. Xu X, Mill J, Zhou K, Brookes K, Chen CK, Asherson P (2007b) Family-based association study between brain-derived neurotrophic factor gene polymorphisms and attention deficit hyperactivity disorder in UK and Taiwanese samples. Am J Med Genet B 144B:83–86CrossRefGoogle Scholar
  338. Xu X, Duman EA, Anney R, Brookes K, Franke B, Zhou K, Buschgens C, Chen W, Christiansen H, Eisenberg J, Gabriels I, Manor I, Marco R, Muller UC, Mulligan A, Rommelse N, Thompson M, Uebel H, Banaschewski T, Buitelaar J, Ebstein R, Gill M, Miranda A, Mulas F, Oades RD, Roeyers H, Rothenberger A, Sergeant J, Sonuga-Barke E, Steinhausen HC, Taylor E, Faraone SV, Asherson P (2008) No association between two polymorphisms of the serotonin transporter gene and combined type attention deficit hyperactivity disorder. Am J Med Genet B 147B:1306–1309CrossRefGoogle Scholar
  339. Yang JW, Jang WS, Hong SD, Ji YI, Kim DH, Park J, Kim SW, Joung YS (2008) A case-control association study of the polymorphism at the promoter region of the DRD4 gene in Korean boys with attention deficit-hyperactivity disorder: evidence of association with the -521 C/T SNP. Prog Neuropsychopharmacol Biol Psychiatry 32:243–248PubMedCrossRefGoogle Scholar
  340. Yang-Feng TL, Kobilka BKC MG, Lefkowitz RJ, Francke U (1987) Chromosomal assignment of genes for an alpha-adrenergic receptor (ADRAR) and for another member of this receptor family coupled to guanine nucleotide regulatory proteins (RG21). Cytogenet Cell Genet 46:722–723Google Scholar
  341. Zabetian CP, Anderson GM, Buxbaum SG, Elston RC, Ichinose H, Nagatsu T, Kim KS, Kim CH, Malison RT, Gelernter J, Cubells JF (2001) A quantitative-trait analysis of human plasma-dopamine beta-hydroxylase activity: evidence for a major functional polymorphism at the DBH locus. Am J Hum Genet 68:515–522PubMedCrossRefGoogle Scholar
  342. Zabetian CP, Buxbaum SG, Elston RC, Kohnke MD, Anderson GM, Gelernter J, Cubells JF (2003) The structure of linkage disequilibrium at the DBH locus strongly influences the magnitude of association between diallelic markers and plasma dopamine beta-hydroxylase activity. Am J Hum Genet 72:1389–1400PubMedCrossRefGoogle Scholar
  343. Zametkin A, Rapoport JL, Murphy DL, Linnoila M, Ismond D (1985) Treatment of hyperactive children with monoamine oxidase inhibitors. I. Clinical efficacy. Arch Gen Psychiatry 42:962–966PubMedGoogle Scholar
  344. Zhang XN, Ruan LM, Le YP, Zhang Y (2003) Association analysis between attention-deficit hyperactivity disorder and Val158Met polymorphism of catechol-O-methyltransferase gene. Zhonghua yi xue yi chuan xue za zhi 20:322–324PubMedGoogle Scholar
  345. Zhao AL, Su LY, Zhang YH, Tang BS, Luo XR, Huang CX, Su QR (2005) Association analysis of serotonin transporter promoter gene polymorphism with ADHD and related symptomatology. Int J Neurosci 115:1183–1191PubMedCrossRefGoogle Scholar
  346. Zoroglu SS, Erdal ME, Alasehirli B, Erdal N, Tutkun H, Savas HA, Herken H (2002) Significance of serotonin transporter gene 5-HTTLPR and variable number of tandem repeat polymorphism in attention deficit hyperactivity disorder. Neuropsychobiology 45:176–181PubMedCrossRefGoogle Scholar
  347. Zoroglu SS, Erdal ME, Erdal N, Ozen S, Alasehirli B, Sivasli E (2003) No evidence for an association between the T102C and 1438 G/A polymorphisms of the serotonin receptor gene in attention deficit/hyperactivity disorder in a Tukish population. Neuropsychobiology 47:17–20PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Ian R. Gizer
    • 1
  • Courtney Ficks
    • 2
  • Irwin D. Waldman
    • 2
  1. 1.Department of GeneticsUniversity of North Carolina at Chapel HillChapel HillUSA
  2. 2.Department of PsychologyEmory UniversityAtlantaUSA

Personalised recommendations