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Progress and Promise of Attention-Deficit Hyperactivity Disorder Pharmacogenetics

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Abstract

One strategy for understanding variability in attention-deficit hyperactivity disorder (ADHD) medication response, and therefore redressing the current trial-and-error approach to ADHD medication management, is to identify genetic moderators of treatment. This article summarizes ADHD pharmacogenetic investigative efforts to date, which have primarily focused on short-term response to methylphenidate and largely been limited by modest sample sizes. The most well studied genes include the dopamine transporter and dopamine D4 receptor, with additional genes that have been significantly associated with stimulant medication response including the adrenergic α2A-receptor, catechol-O-methyltransferase, D5 receptor, noradrenaline (norepinephrine) transporter protein 1 and synaptosomal-associated protein 25 kDa.

Unfortunately, results of current ADHD pharmacogenetic studies have not been entirely consistent, possibly due to differences in study design, medication dosing regimens and outcome measures. Future directions for ADHD pharmacogenetics investigations may include examination of drug-metabolizing enzymes and a wider range of stimulant and non-stimulant medications. In addition, researchers are increasingly interested in going beyond the individual candidate gene approach to investigate gene-gene interactions or pathways, effect modification by additional environmental exposures and whole genome approaches. Advancements in ADHD pharmacogenetics will be facilitated by multi-site collaborations to obtain larger sample sizes using standardized protocols. Although ADHD pharmacogenetic efforts are still in a relatively early stage, their potential clinical applications may include the development of treatment efficacy and adverse effect prediction algorithms that incorporate the interplay of genetic and environmental factors, as well as the development of novel ADHD treatments.

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References

  1. Prince JB. Pharmacotherapy of attention-deficit hyper-activity disorder in children and adolescents: update on new stimulant preparations, atomoxetine, and novel treatments. Child Adolesc Psychiatr Clin N Am 2006 Jan; 15(1): 13–50

    Article  PubMed  Google Scholar 

  2. Faraone SV, Biederman J, Spencer TJ, et al. Comparing the efficacy of medications for ADHD using meta-analysis. Med Gen Med 2006; 8(4): 4

    Google Scholar 

  3. Charach A, Ickowicz A, Schachar R. Stimulant treatment over five years: adherence, effectiveness, and adverse effects. J Am Acad Child Adolesc Psychiatry 2004 May; 43(5): 559–67

    Article  PubMed  Google Scholar 

  4. National Institute of Mental Health. National Institute of Mental Health Multimodal Treatment Study of ADHD follow-up: 24-month outcomes of treatment strategies for attention-deficit/hyperactivity disorder. Pediatrics 2004 Apr; 113(4): 754–61

    Article  Google Scholar 

  5. Katusic SK, Barbaresi WJ, Colligan RC, et al. Psychostimulant treatment and risk for substance abuse among young adults with a history of attention-deficit/hyperactivity disorder: a population-based, birth cohort study. J Child Adolesc Psychopharmacol 2005 Oct; 15(5): 764–76

    Article  PubMed  Google Scholar 

  6. Barbaresi WJ, Katusic SK, Colligan RC, et al. Modifiers of long-term school outcomes for children with attention-deficit/hyperactivity disorder: does treatment with stimulant medication make a difference? Results from a population-based study. J Dev Behav Ped 2007 Aug; 28(4): 274–86

    Article  Google Scholar 

  7. Lowe N, Barry E, Gill M, et al. An overview of the pharmacogenetics and molecular genetics of ADHD. Curr Pharmacogen 2006; 4: 231–43

    Article  CAS  Google Scholar 

  8. Faraone SV, Biederman J. Neurobiology of attention-deficit hyperactivity disorder. Biol Psychiatry 1998 Nov 15; 44(10): 951–8

    Article  PubMed  CAS  Google Scholar 

  9. Faraone SV, Perlis RH, Doyle AE, et al. Molecular genetics of attention-deficit/hyperactivity disorder. Biol Psychiatry 2005 Jun 1; 57(11): 1313–23

    Article  PubMed  CAS  Google Scholar 

  10. Weber WW. Pharmacogenetics. New York: Oxford Press,1997

    Google Scholar 

  11. Phillips KA, Veenstra DL, Sadee W. Implications of the genetics revolution for health services research: pharma-cogenomics and improvements in drug therapy. Health Serv Res 2000 Dec; 35(5 Pt 3): 128–40

    PubMed  CAS  Google Scholar 

  12. Aitchison KJ, Gill M. Pharmacogenetics in the postgenomic era. In: Plomin R, Devries J, Craig I, et al., editors. Behavioral genetics in the postgenomic era. Washington, DC: American Psychological Association, 2003

    Google Scholar 

  13. Evans WE, Relling MV. Pharmacogenomics: translating functional genomics into rational therapeutics. Science 1999 Oct 15; 286(5439): 487–91

    Article  PubMed  CAS  Google Scholar 

  14. Staddon S, Arranz MJ, Mancama D, et al. Clinical applicationsof pharmacogenetics in psychiatry. Psycho- pharmacology 2002 Jun; 162(1): 18–23

    CAS  Google Scholar 

  15. Solanto MV. Neuropsychopharmacological mechanisms of stimulant drug action in attention-deficit hyperactivity disorder: a review and integration. Behav Brain Res 1998 Jul; 94(1): 127–52

    Article  PubMed  CAS  Google Scholar 

  16. Eisenberg J, Mei-Tal G, Steinberg A, et al. 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 1999 Oct 15; 88(5): 497–502

    Article  PubMed  CAS  Google Scholar 

  17. Qian Q, Wang Y, Zhou R, et al. 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 Neuro-psychiatr Genet 2003 Apr 1; 118(1): 103–9

    Article  Google Scholar 

  18. Roman T, Schmitz M, Polanczyk GV, et al. Is the alpha-2A adrenergic receptor gene (ADRA2A) associated with attention-deficit/hyperactivity disorder? Am J Med Genet B Neuropsychiatr Genet 2003 Jul 1; 120(1): 116–20

    Article  Google Scholar 

  19. Roman T, Polanczyk GV, Zeni C, et al. Further evidence of the involvement of alpha-2A-adrenergic receptor gene (ADRA2A) in inattentive dimensional scores of attention-deficit/hyperactivity disorder. Mol Psychiatry 2006 Jan; 11(1): 8–10

    Article  PubMed  CAS  Google Scholar 

  20. Schmitz M, Denardin D, Silva TL, et al. Association between alpha-2a-adrenergic receptor gene and ADHDinattentive type. Biol Psychiatry 2006 Nov 15; 60(10): 1028–33

    Article  PubMed  CAS  Google Scholar 

  21. Bobb AJ, Addington AM, Sidransky E, et al. Support for association between ADHD and two candidate genes: NET1 and DRD1. Am J Med Genet B Neuropsychiatr Genet 2005 Apr 5; 134(1): 67–72

    Google Scholar 

  22. Kim CH, Hahn MK, Joung Y, et al. A polymorphism in the norepinephrine transporter gene alters promoter activity and is associated with attention-deficit hyperactivity disorder. Proc Natl Acad Sci U S A 2006 Dec 12; 103(50): 19164–9

    Article  PubMed  CAS  Google Scholar 

  23. McGough JJ. Attention-deficit/hyperactivity disorder pharmacogenomics. Biol Psychiatry 2005 Jun 1; 57(11): 1367–73

    Article  PubMed  CAS  Google Scholar 

  24. Polanczyk G, Zeni C, Genro JP, et al. Association of the adrenergic alpha2A receptor gene with methylphenidate improvement of inattentive symptoms in children and adolescents with attention-deficit/hyperactivity disorder. Arch Gen Psychiatry 2007 Feb; 64(2): 218–24

    Article  PubMed  CAS  Google Scholar 

  25. da Silva TL, Pianca TG, Roman T, et al. Adrenergic alpha2A receptor gene and response to methylphenidate in attention-deficit/hyperactivity disorder-predominantly inattentive type. J Neural Transm 2008; 115(2): 341–5

    Article  PubMed  CAS  Google Scholar 

  26. Kereszturi E, Tarnok Z, Bognar E, et al. Catechol-O-methyltransferase Val158Met polymorphism is associated with methylphenidate response in ADHD children. Am J Med Genet B Neuropsychiatr Genet 2008 Jan 23; 147B(8): 1431–5

    Article  PubMed  CAS  Google Scholar 

  27. Stein MA, Waldman ID, Sarampote CS, et al. Dopamine transporter genotype and methylphenidate dose responsein children with ADHD. Neuropsychopharmacology 2005 Jul; 30(7): 1374–82

    PubMed  CAS  Google Scholar 

  28. McGough J, McCracken J, Swanson J, et al. Pharmacogenetics of methylphenidate response in preschoolers with ADHD. J Am Acad Child Adolesc Psychiatry 2006 Nov; 45(11): 1314–22

    Article  PubMed  Google Scholar 

  29. Joober R, Grizenko N, Sengupta S, et al. Dopamine transporter 3′-UTR VNTR genotype and ADHD: a pharmaco-behavioural genetic study with methylphenidate. Neuropsychopharmacology 2007 Jun; 32(6): 1370–6

    Article  PubMed  CAS  Google Scholar 

  30. Winsberg BG, Comings DE. Association of the dopamine transporter gene (DAT1) with poor methylphenidate response. J Am Acad Child Adolesc Psychiatry 1999 Dec; 38(12): 1474–7

    Article  PubMed  CAS  Google Scholar 

  31. Roman T, Szobot C, Martins S, et al. Dopamine transporter gene and response to methylphenidate in attention-deficit/hyperactivity disorder. Pharmacogenetics 2002 Aug; 12(6): 497–9

    Article  PubMed  CAS  Google Scholar 

  32. Kirley A, Lowe N, Hawi Z, et al. Association of the 480 bp DAT1 allele with methylphenidate response in a sample of Irish children with ADHD. Am J Med Genet B Neuropsychiatr Genet 2003 Aug 15; 121(1): 50–4

    Article  Google Scholar 

  33. Cheon KA, Ryu YH, Kim JW, et al. The homozygosity for 10-repeat allele at dopamine transporter gene and dopamine transporter density in Korean children with attention deficit hyperactivity disorder: relating to treatment response to methylphenidate. Eur Neuropsycho-pharmacol 2005 Jan; 15(1): 95–101

    Article  CAS  Google Scholar 

  34. Langley K, Turic D, Peirce TR, et al. No support for association between the dopamine transporter (DAT1) gene and ADHD. Am J Med Genet B Neuropsychiatr Genet 2005 Nov 5; 139(1): 7–10

    Google Scholar 

  35. van der Meulen EM, Bakker SC, Pauls DL, et al. High sibling correlation on methylphenidate response but no association with DAT1-10R homozygosity in Dutch sib-pairs with ADHD. J Child Psychol Psychiatry 2005 Oct; 46(10): 1074–80

    Article  PubMed  Google Scholar 

  36. Bellgrove MA, Barry E, Johnson KA, et al. Spatial attentional bias as a marker of genetic risk, symptom severity, and stimulant response in ADHD. Neuropsycho-pharmacology 2008 Nov 28; 33: 2536–45

    Article  CAS  Google Scholar 

  37. Zeni CP, Guimaraes AP, Polanczyk GV, et al. No significant association between response to methylphenidate and genes of the dopaminergic and serotonergic systems in a sample of Brazilian children with attention-deficit/ hyperactivity disorder. Am J Med Genet B Neuropsychiatr Genet 2007 Apr 5; 144(3): 391–4

    Google Scholar 

  38. Purper-Ouakil D, Wohl M, Orejarena S, et al. Pharmaco-genetics of methylphenidate response in attention deficit/ hyperactivity disorder: association with the dopamine transporter gene (SLC6A3). Am J Med Genet B Neuropsychiatr Genet 2008 Jun 18; 147B(8): 1425–30

    Article  PubMed  CAS  Google Scholar 

  39. Tharoor H, Lobos EA, Todd RD, et al. Association of dopamine, serotonin, and nicotinic gene polymorphisms with methylphenidate response in ADHD. Am J Med Genet B Neuropsychiatr Genet 2008 Jun 5; 147B(4): 527–30

    Article  PubMed  Google Scholar 

  40. Tahir E, Yazgan Y, Cirakoglu B, et al. Association and linkage of DRD4 and DRD5 with attention deficit hyperactivity disorder (ADHD) in a sample of Turkish children. Mol Psychiatry 2000 Jul; 5(4): 396–404

    Article  PubMed  CAS  Google Scholar 

  41. Seeger G, Schloss P, Schmidt MH. Marker gene polymorphisms in hyperkinetic disorder: predictors of clinical response to treatment with methylphenidate? Neurosci Lett 2001 Nov 2; 313(1–2): 45–8

    Article  PubMed  CAS  Google Scholar 

  42. Hamarman S, Fossella J, Ulger C, et al. Dopamine receptor 4 (DRD4) 7-repeat allele predicts methylphenidate dose response in children with attention deficit hyperactivity disorder: a pharmacogenetic study. J Child Adolesc Psychopharmacol 2004; 14(4): 564–74

    Article  PubMed  Google Scholar 

  43. Cheon KA, Kim BN, Cho SC. Association of 4-repeat allele of the dopamine D4 receptor gene exon III polymorphism and response to methylphenidate treatment in Korean ADHD children. Neuropsychopharmacology 2007 Jun; 32(6): 1377–83

    Article  PubMed  CAS  Google Scholar 

  44. Yang L, Wang YF, Li J, et al. Association of norepine- phrine transporter gene with methylphenidate response. J Am Acad Child Adolesc Psychiatry 2004 Sep; 43(9): 1154–8

    Article  PubMed  Google Scholar 

  45. Mick E, Biederman J, Spencer T, et al. Absence of association with DAT1 polymorphism and response to methylphenidate in a sample of adults with ADHD. Am J Med Genet B Neuropsychiatr Genet 2006 Dec 5; 141(8): 890–4

    Google Scholar 

  46. Kooij JS, Boonstra AM, Vermeulen SH, et al. Response to methylphenidate in adults with ADHD is associated with a polymorphism in SLC6A3 (DAT1). Am J Med Genet B Neuropsychiatr Genet 2008 Mar 5; 147B(2): 201–8

    Article  PubMed  CAS  Google Scholar 

  47. Polanczyk G, Faraone SV, Bau CH, et al. The impact of individual and methodological factors in the variability of response to methylphenidate in ADHD pharmacogenetic studies from four different continents. Am J Med Genet B Neuropsychiatr Genet 2008 Dec 5; 147B(8): 1419–24

    Article  PubMed  CAS  Google Scholar 

  48. Jorgensen A, Alfirevic A. Pharmacogenetics and pharma-cogenomics: adverse drug reactions. Pharmacogenomics 2008 Oct; 9(10): 1397–401

    Article  PubMed  Google Scholar 

  49. Wadelius M, Pirmohamed M. Pharmacogenetics of warfarin: current status and future challenges. Pharmacogen J 2007 Apr; 7(2): 99–111

    Article  CAS  Google Scholar 

  50. Volkow ND, Fowler JS, Wang G, et al. Mechanism of action of methylphenidate: insights from PET imaging studies. J Atten Disord 2002; 6Suppl. 1: S31–43

    PubMed  Google Scholar 

  51. Melega WP, Williams AE, Schmitz DA, et al. Pharmaco-kinetic and pharmacodynamic analysis of the actions of D-amphetamine and D-methamphetamine on the dopamine terminal. J Pharmacol Exper Ther 1995 Jul; 274(1): 90–6

    CAS  Google Scholar 

  52. Cook Jr EH, Stein MA, Krasowski MD, et al. Association of attention-deficit disorder and the dopamine transporter gene. Am J Hum Genet 1995 Apr; 56(4): 993–8

    PubMed  CAS  Google Scholar 

  53. VanNess SH, Owens MJ, Kilts CD. The variable number of tandem repeats element in DAT1 regulates in vitro dopamine transporter density. BMC Genet 2005; 6: 55

    Article  PubMed  CAS  Google Scholar 

  54. Brookes K, Xu X, Chen W, et al. 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 2006 Oct; 11(10): 934–53

    Article  PubMed  CAS  Google Scholar 

  55. Asherson P, Brookes K, Franke B, et al. Confirmation that a specific haplotype of the dopamine transporter gene is associated with combined-type ADHD. Am J Psychiatry 2007 Apr; 164(4): 674–7

    Article  PubMed  Google Scholar 

  56. Brookes KJ, Mill J, Guindalini C, et al. 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 2006 Jan; 63(1): 74–81

    Article  PubMed  CAS  Google Scholar 

  57. Lott DC, Kim SJ, Cook Jr EH, et al. Dopamine transporter gene associated with diminished subjective response to amphetamine. Neuropsychopharmacology 2005 Mar; 30(3): 602–9

    Article  PubMed  CAS  Google Scholar 

  58. Heckers S, Konradi C. Synaptic function and biochemical neuroanatomy. In: Martin A, Scahill L, Charney DS, et al., editors. Pediatric psychopharmacology: principles and practice. New York: Oxford University Press, 2003: 20–32

    Google Scholar 

  59. Asghari V, Sanyal S, Buchwaldt S, et al. Modulation of intracellular cyclic AMP levels by different human dopamine D4 receptor variants. J Neurochem 1995 Sep; 65(3): 1157–65

    Article  PubMed  CAS  Google Scholar 

  60. Van Tol HH, Wu CM, Guan HC, et al. Multiple dopamine D4 receptor variants in the human population. Nature 1992 Jul 9; 358(6382): 149–52

    Article  PubMed  Google Scholar 

  61. Sallee FR, Newcorn J, Allen AJ, et al. Pharmacogenetics of atomoxetine: relevance of DRD4. Scientific proceedings of the 51st Annual Meeting of the American Academy of Child and Adolescent Psychiatry; 2004 Oct 21; Washington, DC: 28

  62. Nestler EJ, Hyman SE, Malenka RC. Molecular neuro-pharmacology: a foundation for clinical neuroscience. New York: The McGraw-Hill Companies, Inc., 2001

  63. Arnsten AF, Dudley AG. Methylphenidate improves prefrontal cortical cognitive function through alpha2 adrenoceptor and dopamine D1 receptor actions: relevance to therapeutic effects in attention deficit hyperactivity disorder. Behav Brain Funct 2005 Apr 22; 1(1): 2

    Article  PubMed  CAS  Google Scholar 

  64. Andrews GD, Lavin A. Methylphenidate increases cortical excitability via activation of alpha-2 noradrenergic receptors. Neuropsychopharmacology 2006 Mar; 31(3): 594–601

    Article  PubMed  CAS  Google Scholar 

  65. Lario S, Calls J, Cases A, et al. MspI identifies a biallelic polymorphism in the promoter region of the alpha 2A-adrenergic receptor gene. Clin Genet 1997 Feb; 51(2): 129–30

    Article  PubMed  CAS  Google Scholar 

  66. Deupree JD, Smith SD, Kratochvil CJ, et al. Possible involvement of alpha-2A adrenergic receptors in attention deficit hyperactivity disorder: radioligand binding and polymorphism studies. Am J Med Genet B Neuro-psychiatr Genet 2006 Dec 5; 141B(8): 877–84

    Article  CAS  Google Scholar 

  67. Lachman HM, Papolos DF, Saito T, et al. Human catechol-O-methyltransferase pharmacogenetics: description of a functional polymorphism and its potential application to neuropsychiatric disorders. Pharmacogenetics 1996 Jun; 6(3): 243–50

    Article  PubMed  CAS  Google Scholar 

  68. Cheuk DK, Wong V. Meta-analysis of association between a catechol-O-methyltransferase gene polymorphism and attention deficit hyperactivity disorder. Behav Genet 2006 Sep;36(5):651–9

    Article  PubMed  Google Scholar 

  69. Mattay VS, Goldberg TE, Fera F, et al. Catechol-O-methyltransferase val158-met genotype and individual variation in the brain response to amphetamine. Proc Natl Acad Sci U S A 2003 May 13; 100(10): 6186–91

    Article  PubMed  CAS  Google Scholar 

  70. Holmes A, Hollon TR, Gleason TC, et al. Behavioral characterization of dopamine D5 receptor null mutant mice. Behav Neurosci 2001 Oct; 115(5): 1129–44

    Article  PubMed  CAS  Google Scholar 

  71. Lowe N, Kirley A, Hawi Z, et al. 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 2004 Feb; 74(2): 348–56

    Article  PubMed  CAS  Google Scholar 

  72. Maher BS, Marazita ML, Ferrell RE, et al. Dopamine system genes and attention deficit hyperactivity disorder: a meta-analysis. Psychiatr Genet 2002 Dec; 12(4): 207–15

    Article  PubMed  Google Scholar 

  73. Li D, Sham PC, Owen MJ, et al. Meta-analysis shows significant association between dopamine system genes and attention deficit hyperactivity disorder (ADHD). Hum Mol Genet 2006 Jul 15; 15(14): 2276–84

    Article  PubMed  CAS  Google Scholar 

  74. Berridge CW, Devilbiss DM, Andrzejewski ME, et al. Methylphenidate preferentially increases catecholamine neurotransmission within the prefrontal cortex at low doses that enhance cognitive function. Biol Psychiatry 2006 Nov 15; 60(10): 1111–20

    Article  PubMed  CAS  Google Scholar 

  75. Michelson D, Faries D, Wernicke J, et al. Atomoxetine in the treatment of children and adolescents with attention-deficit/hyperactivity disorder: a randomized, placebo-controlled, dose-response study. Pediatrics 2001 Nov; 108(5): E83

    Article  PubMed  CAS  Google Scholar 

  76. Forero DA, Arboleda GH, Vasuez R, et al. Candidate genes involved in neural plasticity and the risk for attention-deficit hyperactivity disorder: a meta-analysis of 8 common variants. J Psychiatry Neurosci 2009; 34(5): 361–6

    PubMed  Google Scholar 

  77. Dlugos A, Freitag C, Hohoff C, et al. Norepinephrine transporter gene variation modulates acute response to D-amphetamine. Biol Psychiatry 2007 Jun 1; 61(11): 1296–305

    Article  PubMed  CAS  Google Scholar 

  78. Schiavo G, Stenbeck G, Rothman JE, et al. Binding of the synaptic vesicle v-SNARE, synaptotagmin, to the plasma membrane t-SNARE, SNAP-25, can explain docked vesicles at neurotoxin-treated synapses. Proc Natl Acad Sci U S A 1997 Feb 4; 94(3): 997–1001

    Article  PubMed  CAS  Google Scholar 

  79. Barr CL, Feng Y, Wigg K, et al. Identification of DNA variants in the SNAP-25 gene and linkage study of these polymorphisms and attention-deficit hyperactivity disorder. Mol Psychiatry 2000 Jul; 5(4): 405–9

    Article  PubMed  CAS  Google Scholar 

  80. Brophy K, Hawi Z, Kirley A, et al. Synaptosomal-associated protein 25 (SNAP-25) and attention deficit hyperactivity disorder (ADHD): evidence of linkage and association in the Irish population. Mol Psychiatry 2002; 7(8): 913–7

    Article  PubMed  CAS  Google Scholar 

  81. Kustanovich V, Merriman B, McGough J, et al. Biased paternal transmission of SNAP-25 risk alleles in attention-deficit hyperactivity disorder. Mol Psychiatry 2003 Mar; 8(3): 309–15

    Article  PubMed  CAS  Google Scholar 

  82. Mill J, Curran S, Kent L, et al. Association study of a SNAP-25 microsatellite and attention deficit hyperactivity disorder. Am J Med Genet 2002 Apr 8; 114(3): 269–71

    Article  PubMed  Google Scholar 

  83. Wilson MC. Coloboma mouse mutant as an animal model of hyperkinesis and attention deficit hyperactivity disorder. Neurosci Biobehav Rev 2000 Jan; 24(1): 51–7

    Article  PubMed  CAS  Google Scholar 

  84. Polanczyk G, Zeni C, Genro JP, et al. Attention-deficit/ hyperactivity disorder: advancing on pharmacogenomics. Pharmacogenomics 2005 Apr; 6(3): 225–34

    Article  PubMed  CAS  Google Scholar 

  85. Sun Z, Murry DJ, Sanghani SP, et al. Methylphenidate is stereoselectively hydrolyzed by human carboxylesterase CES1 A1. J Pharmacol Exper Ther 2004 Aug; 310(2): 469–76

    Article  CAS  Google Scholar 

  86. Zhu HJ, Patrick KS, Yuan HJ, et al. Two CES1 gene mutations lead to dysfunctional carboxylesterase 1 activity in man: clinical significance and molecular basis. Am J Hum Genet 2008 Jun; 82(6): 1241–8

    Article  PubMed  CAS  Google Scholar 

  87. Dring LG, Smith RL, Williams RT. The metabolic fate of amphetamine in man and other species. Biochemical J 1970 Feb; 116(3): 425–35

    CAS  Google Scholar 

  88. Markowitz JS, Patrick KS. Pharmacokinetic and pharma-codynamic drug interactions in the treatment of attention-deficit hyperactivity disorder. Clin Pharmacokinet 2001; 40(10): 753–72

    Article  PubMed  CAS  Google Scholar 

  89. Meyer UA, Zanger UM. Molecular mechanisms of genetic polymorphisms of drug metabolism. Annu Rev Pharmacol Toxicol 1997; 37: 269–96

    Article  PubMed  CAS  Google Scholar 

  90. McGough JJ, Biederman J, Greenhill LL, et al. Pharma-cokinetics of SLI381 (ADDERALL XR) an extended release formulation of Adderall. J Am Acad Child Adolesc Psychiatry 2003; 42(6): 684–91

    Article  PubMed  Google Scholar 

  91. Wandel C, Witte JS, Hall JM, et al. CYP3A activity in African American and European American men: population differences and functional effect of the CYP3 A4* 1 B5′-promoter region polymorphism. Clin Pharmacol Ther 2000 Jul; 68(1): 82–91

    Article  PubMed  CAS  Google Scholar 

  92. Michelson D, Read HA, Ruff DD, et al. CYP2D6 and clinical response to atomoxetine in children and adolescents with ADHD. J Am Acad Child Adolesc Psychiatry 2007 Feb; 46(2): 242–51

    Article  PubMed  Google Scholar 

  93. Waldman ID, Gizer IR. The genetics of attention deficit hyperactivity disorder. Clin Psychol Rev 2006 Aug; 26(4): 396–432

    Article  PubMed  Google Scholar 

  94. Friedel S, Saar K, Sauer S, et al. Association and linkage of allelic variants of the dopamine transporter gene in ADHD. Mol Psychiatry 2007 Oct; 12(10): 923–33

    Article  PubMed  CAS  Google Scholar 

  95. Van der Meulen EM, Bakker SC, Pauls DL, et al. A genome-widequantitative trait locus analysis on methylphenidate response rate in Dutch sibpairs with attention-deficit/ hyperactivity disorder. 16th World Congress of the International Association for Child and Adolescent Psychiatry and Allied Professions; 2004 Aug 22–26; Berlin

  96. Mick E, Neale B, Middleton FA, et al. Genome-wide association study of response to methylphenidate in 187 children with attention-deficit/hyperactivity disorder. Am J Med Genet B Neuropsych Genet 2008 Sep; 147B: 7412–4

    Google Scholar 

  97. Pelham WE, Millich R. Individual differences in response to Ritalin in class work and social behavior. In: Greenhill L, Osman B, editors. Ritalin: theory and patient management. New York: Mary Ann Liebert, 1991

    Google Scholar 

  98. Brody AL, Mandelkern MA, Olmstead RE, et al. Gene variants of brain dopamine pathways and smoking-induced dopamine release in the ventral caudate/nucleus accumbens. Arch Gen Psychiatry 2006 Jul; 63(7): 808–16

    Article  PubMed  CAS  Google Scholar 

  99. Li S, Kim KY, Kim JH, et al. Chronic nicotine and smoking treatment increases dopamine transporter mRNA expression in the rat midbrain. Neurosci Lett 2004 Jun 3; 363(1): 29–32

    Article  PubMed  CAS  Google Scholar 

  100. Gerasimov MR, Franceschi M, Volkow ND, et al. Synergistic interactions between nicotine and cocaine or methylphenidate depend on the dose of dopamine transporter inhibitor. Synapse 2000 Dec 15; 38(4): 432–7

    Article  PubMed  CAS  Google Scholar 

  101. Weinshilboum RM, Wang L. Pharmacogenetics and pharmacogenomics: development, science, and translation. Annu Rev Genom Human Genet 2006; 7: 223–45

    Article  CAS  Google Scholar 

  102. ADHD Molecular Genetics Network Annual International Meeting; 2006 Oct 8–10; Brussels

  103. ADHD Molecular Genetics Network Annual International Meeting; 2008 Dec 5–7; Sanibel Island (FL)

  104. Pliszka SR, Crismon ML, Hughes CW, et al. The Texas Children’s Medication Algorithm Project: revision of the algorithm for pharmacotherapy of attention-deficit/ hyperactivity disorder. J Am Acad Child Adolesc Psychiatry 2006 Jun; 45(6): 642–57

    Article  PubMed  Google Scholar 

  105. McGough JJ, Biederman J, Wigal SB, et al. Long-term tolerability and effectiveness of once-daily mixed amphetamine salts (Adderall XR) in children with ADHD. J Am Acad Child Adolesc Psychiatry 2005 Jun; 44(6): 530–8

    Article  PubMed  Google Scholar 

  106. Wilens T, Pelham W, Stein M, et al. ADHD treatment with once-daily OROS methylphenidate: interim 12-month results from a long-term open-label study. J Am Acad Child Adolesc Psychiatry 2003 Apr; 42(4): 424–33

    Article  PubMed  Google Scholar 

  107. Wigal T, Greenhill L, Chuang S, et al. Safety and tolerability of methylphenidate in preschool children with ADHD. J Am Acad Child Adolesc Psychiatry 2006 Nov; 45(11): 1294–303

    Article  PubMed  Google Scholar 

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Acknowledgements

Dr Stein has received research support from McNeil, Novartis, Eli Lilly & Co., Cortex Pharmaceuticals, Organon and Pfizer Pharmaceuticals, and serves as a consultant for Novartis Pharmaceuticals and Shire Pharmaceuticals. Dr McGough has served as a consultant to or received research support from Eli Lilly & Co., Janssen Pharmaceuticals and Shire Pharmaceuticals. Dr Froehlich has no conflicts of interest that are directly relevant to the contents of this review. No funding organizations had any role in the preparation, review or approval of this manuscript.

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Authors and Affiliations

  1. Division of Developmental and Behavioral Pediatrics, Department of Pediatrics, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, USA

    Tanya E. Froehlich

  2. Division of Child and Adolescent Psychiatry, University of California, Los Angeles Semel Institute for Neuroscience and Human Behavior, Los Angeles, California, USA

    James J. McGough

  3. UCLA Child and Adolescent Psychopharmacology Program and ADHD Clinic, Los Angeles, California, USA

    James J. McGough

  4. Department of Psychiatry, University of Illinois at Chicago, Chicago, Illinois, USA

    Mark A. Stein

  5. Hyperactivity, Attention, and Learning Problems (HALP) Clinic and ADHD Research Center, University of Illinois at Chicago, Chicago, Illinois, USA

    Mark A. Stein

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Correspondence to Mark A. Stein.

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Froehlich, T.E., McGough, J.J. & Stein, M.A. Progress and Promise of Attention-Deficit Hyperactivity Disorder Pharmacogenetics. CNS Drugs 24, 99–117 (2010). https://doi.org/10.2165/11530290-000000000-00000

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