Journal of the Korean Academy of Child and Adolescent Psychiatry

Korean Academy of Child and Adolescent Psychiatry (대한소아청소년정신의학회)
권호 표지
DOI QR코드

DOI QR Code

Association of Norepinephrine Transporter Gene and Side Effects of Osmotic-Release Oral System Methylphenidate in Attention-Deficit Hyperactivity Disorder

주의력결핍 과잉행동장애에서 노르에피네프린 수송체 유전자와 오로스 메칠페니데이트 부작용의 연관성

  • Song, Jungeun (Department of Psychiatry, National Health Insurance Service Ilsan Hospital) ;
  • Hong, Hyun Ju (Department of Psychiatry, Hallym University College of Medicine) ;
  • Lee, Byung Ook (Department of Psychiatry, National Health Insurance Service Ilsan Hospital) ;
  • Yook, Ki-Hwan (Department of Psychiatry, CHA Bundang Medical Center, School of Medicine, CHA University)
  • 송정은 (국민건강보험 일산병원 정신건강의학과) ;
  • 홍현주 (한림대학교 의과대학 정신건강의학교실) ;
  • 이병욱 (국민건강보험 일산병원 정신건강의학과) ;
  • 육기환 (CHA의과학대학교 분당차병원 정신건강의학교실)
  • Received : 2013.10.02
  • Accepted : 2014.05.20
  • Published : 2014.06.30
Download PDF
⟨ Previous Next ⟩

Abstract

Objectives : The aim of our study was to investigate association of norepinephrine transporter gene (SLC6A2) polymorphism and side effects of osmotic-release oral system methylphenidate (OROS MPH) in children with attention-deficit hyperactivity disorder (ADHD). Methods : We recruited drug naive children with ADHD (N=97). We administered OROS MPH by tolerable dosage. At week 8 of treatment, parents completed the Barkley's side effect rating scale. We analyzed two SLC6A2 single nucleotide polymorphisms (SNPs), rs192303 and rs3785143, with blood of subjects. We compared the frequency and severity of each side effect among SLC6A2 genotypes of 2 SNPs. Results : In the analysis of frequency of each side effect, irritability differed according to rs192303 and rs3785143 genotype. In comparisons of severity, talking less and disinterest differed according to rs192303 genotype. In the case of rs3785143, severities of disinterest and irritability were involved with genotype. Conclusion : Side effects of OROS MPH showed an association with SLC6A2 genotype.

Keywords

References

  1. Polanczyk G, de Lima MS, Horta BL, Biederman J, Rohde LA. The worldwide prevalence of ADHD: a systematic review and metaregression analysis. Am J Psychiatry 2007;164:942-948. https://doi.org/10.1176/appi.ajp.164.6.942
  2. Vaughan B, Kratochvil CJ. Pharmacotherapy of pediatric attentiondeficit/ hyperactivity disorder. Child Adolesc Psychiatr Clin N Am 2012;21:941-955. https://doi.org/10.1016/j.chc.2012.07.005
  3. Adler LD, Nierenberg AA. Review of medication adherence in children and adults with ADHD. Postgrad Med 2010;122:184-191. https://doi.org/10.3810/pgm.2010.01.2112
  4. Toomey SL, Sox CM, Rusinak D, Finkelstein JA. Why do children with ADHD discontinue their medication? Clin Pediatr (Phila) 2012;51:763-769. https://doi.org/10.1177/0009922812446744
  5. Efron D, Jarman FC, Barker MJ. Child and parent perceptions of stimulant medication treatment in attention deficit hyperactivity disorder. J Paediatr Child Health 1998;34:288-292. https://doi.org/10.1046/j.1440-1754.1998.00224.x
  6. A 14-month randomized clinical trial of treatment strategies for attention- deficit/hyperactivity disorder. The MTA Cooperative Group. Multimodal Treatment Study of Children with ADHD. Arch Gen Psychiatry 1999;56:1073-1086. https://doi.org/10.1001/archpsyc.56.12.1073
  7. Wilens TE, McBurnett K, Bukstein O, McGough J, Greenhill L, Lerner M, et al. Multisite controlled study of OROS methylphenidate in the treatment of adolescents with attention-deficit/hyperactivity disorder. Arch Pediatr Adolesc Med 2006;160:82-90. https://doi.org/10.1001/archpedi.160.1.82
  8. Wilens T, Pelham W, Stein M, Conners CK, Abikoff H, Atkins 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;42:424-433. https://doi.org/10.1097/01.CHI.0000046814.95464.7D
  9. Kim BS, Park EJ. An observational multi-center study for evaluation of efficacy, safety and parental satisfaction of methylphenidate- OROS in children with ADHD. J Korean Acad Child Adolesc Psychiatry 2005;16:279-285.
  10. Wilens TE. Effects of methylphenidate on the catecholaminergic system in attention-deficit/hyperactivity disorder. J Clin Psychopharmacol 2008;28(3 Suppl 2):S46-S53. https://doi.org/10.1097/JCP.0b013e318173312f
  11. Levy F, Wimalaweera S, Moul C, Brennan J, Dadds MR. Dopamine receptors and the pharmacogenetics of side-effects of stimulant treatment for attention-deficit/hyperactivity disorder. J Child Adolesc Psychopharmacol 2013;23:423-425. https://doi.org/10.1089/cap.2013.0006
  12. McGough J, McCracken J, Swanson J, Riddle M, Kollins S, Greenhill L, et al. Pharmacogenetics of methylphenidate response in preschoolers with ADHD. J Am Acad Child Adolesc Psychiatry 2006; 45:1314-1322. https://doi.org/10.1097/01.chi.0000235083.40285.08
  13. Stein MA, Waldman ID, Sarampote CS, Seymour KE, Robb AS, Conlon C, et al. Dopamine transporter genotype and methylphenidate dose response in children with ADHD. Neuropsychopharmacology 2005;30:1374-1382. https://doi.org/10.1038/sj.npp.1300718
  14. Zeni CP, Guimarães AP, Polanczyk GV, Genro JP, Roman T, Hutz MH, 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;144B: 391-394. https://doi.org/10.1002/ajmg.b.30474
  15. Gruber R, Joober R, Grizenko N, Leventhal BL, Cook EH Jr, Stein MA. Dopamine transporter genotype and stimulant side effect factors in youth diagnosed with attention-deficit/hyperactivity disorder. J Child Adolesc Psychopharmacol 2009;19:233-239. https://doi.org/10.1089/cap.2008.0133
  16. Berridge CW, Devilbiss DM, Andrzejewski ME, Arnsten AF, Kelley AE, Schmeichel B, et al. Methylphenidate preferentially increases catecholamine neurotransmission within the prefrontal cortex at low doses that enhance cognitive function. Biol Psychiatry 2006; 60:1111-1120. https://doi.org/10.1016/j.biopsych.2006.04.022
  17. Bobb AJ, Addington AM, Sidransky E, Gornick MC, Lerch JP, Greenstein DK, et al. Support for association between ADHD and two candidate genes: NET1 and DRD1. Am J Med Genet B Neuropsychiatr Genet 2005;134B:67-72. https://doi.org/10.1002/ajmg.b.30142
  18. Brookes K, Xu X, Chen W, Zhou K, Neale B, Lowe N, 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;11:934-953. https://doi.org/10.1038/sj.mp.4001869
  19. Joung Y, Kim CH, Moon J, Jang WS, Yang J, Shin D, et al. Association studies of -3081(A/T) polymorphism of norepinephrine transporter gene with attention deficit/hyperactivity disorder in Korean population. Am J Med Genet B Neuropsychiatr Genet 2010;153B: 691-694. https://doi.org/10.1002/ajmg.b.31012
  20. Kim CH, Waldman ID, Blakely RD, Kim KS. Functional gene variation in the human norepinephrine transporter: association with attention deficit hyperactivity disorder. Ann N Y Acad Sci 2008; 1129:256-260. https://doi.org/10.1196/annals.1417.023
  21. Xu X, Knight J, Brookes K, Mill J, Sham P, Craig I, et al. DNA pooling analysis of 21 norepinephrine transporter gene SNPs with attention deficit hyperactivity disorder: no evidence for association. Am J Med Genet B Neuropsychiatr Genet 2005;134B:115-118. https://doi.org/10.1002/ajmg.b.30160
  22. Mick E, Neale B, Middleton FA, McGough JJ, Faraone SV. Genome-wide association study of response to methylphenidate in 187 children with attention-deficit/hyperactivity disorder. Am J Med Genet B Neuropsychiatr Genet 2008;147B:1412-1418. https://doi.org/10.1002/ajmg.b.30865
  23. Yang L, Wang YF, Li J, Faraone SV. Association of norepinephrine transporter gene with methylphenidate response. J Am Acad Child Adolesc Psychiatry 2004;43:1154-1158. https://doi.org/10.1097/01.chi.0000131134.63368.46
  24. So YK, Noh JS, Kim YS, Ko SG, Koh YJ. The reliability and validity of Korean parent and teacher ADHD Rating Scale. J Korean Neuropsychiatr Assoc 2002;41:283-289.
  25. Kim YS, Cheon KA, Kim BN, Chang SA, Yoo HJ, Kim JW, et al. The reliability and validity of Kiddie-Schedule for Affective Disorders and Schizophrenia-Present and Lifetime Version- Korean version (K-SADS-PL-K). Yonsei Med J 2004;45:81-89. https://doi.org/10.3349/ymj.2004.45.1.81
  26. Barkley RA, McMurray MB, Edelbrock CS, Robbins K. Side effects of methylphenidate in children with attention deficit hyperactivity disorder: a systemic, placebo-controlled evaluation. Pediatrics 1990;86:184-192.
  27. Bruss M, Kunz J, Lingen B, Bonisch H. Chromosomal mapping of the human gene for the tricyclic antidepressant-sensitive noradrenaline transporter. Hum Genet 1993;91:278-280.
  28. Cho SC, Kim BN, Cummins TD, Kim JW, Bellgrove MA. Norepinephrine transporter -3081(A/T) and alpha-2A-adrenergic receptor MspI polymorphisms are associated with cardiovascular side effects of OROS-methylphenidate treatment. J Psychopharmacol 2012;26:380-389. https://doi.org/10.1177/0269881111405356
  29. Kim CH, Kim HS, Cubells JF, Kim KS. A previously undescribed intron and extensive 5’ upstream sequence, but not Phox2a-mediated transactivation, are necessary for high level cell type-specific expression of the human norepinephrine transporter gene. J Biol Chem 1999;274:6507-6518. https://doi.org/10.1074/jbc.274.10.6507
  30. Karabekiroglu K, Yazgan YM, Dedeoglu C. Can we predict shortterm side effects of methylphenidate immediate-release? Int J Psychiatry Clin Pract 2008;12:48-54. https://doi.org/10.1080/13651500701435954

Cited by

  1. Dimorphic association of dopaminergic transporter gene variants with treatment outcome: Pilot study in Indian ADHD probands vol.11, 2017, https://doi.org/10.1016/j.mgene.2016.11.007