Dopamine transporter genotype and methylphenidate dose response in children with ADHD

Mark A. Stein, Irwin D. Waldman, Christopher S. Sarampote, Karen E. Seymour, Adelaide S. Robb, Charles Conlon, Soo Jeong Kim, Edwin H. Cook

Research output: Contribution to journalArticlepeer-review

Abstract

Stimulant medications, such as methylphenidate (MPH), are the most commonly used, effective treatment for ADHD. MPH acts primarily by inhibiting the dopamine transporter (DAT), a protein responsible for the reuptake of dopamine from the synapse into presynaptic terminals. We sought to evaluate the relationship between DAT1 3′-untranslated region (3′-UTR) variable number tandem repeats (VNTR) genotypes and dose response to MPH. Children with ADHD (n = 47), ages 5-16 years (mean = 9.02 years), underwent a 4-week, double-blinded, crossover trial with forced weekly dosage changes. Children were genotyped for the DAT1 VNTR and evaluated on placebo and three dosage levels of OROS® MPH. Parents and clinicians who were blind to genotype and medication status rated ADHD symptoms, impairment, and stimulant side effects each week. Children who were homozygous for the less common, 9-repeat DAT1 3′-UTR genotype displayed a distinct dose-response curve from that of the other genotype groups, with an absence of typical linear improvement when the dose was increased from 18 mg to 36 and 54 mg. Further research is needed to determine the mechanisms related to poor response in patients with the 9/9-repeat genotype, and to determine if this group responds differentially to alternative treatments.

Original languageEnglish (US)
Pages (from-to)1374-1382
Number of pages9
JournalNeuropsychopharmacology
Volume30
Issue number7
DOIs
StatePublished - Jul 2005
Externally publishedYes

Keywords

  • ADHD
  • Dopamine transporter
  • Methylphenidate
  • Pharmacogenetics

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health

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