title: Dopamine transporter genotype and stimulant dose-response in youth with attention-deficit/hyperactivity disorder.
abstract: OBJECTIVE
  This study seeks to determine if variation in the dopamine transporter gene (SLC6A3/DAT1) moderates the dose-response effects of long-acting dexmethylphenidate (D-MPH) and mixed amphetamine salts (MAS) in children with attention-deficit/hyperactivity disorder (ADHD).
  
  
  METHODS
  Fifty-six children and adolescents (mean age=11.7±2.2) participated in a double-blind, two period crossover, dose-response study with a randomized placebo week in each 4 week drug period. Each period consisted of sequential week-long exposures to three dose levels (10, 20, 25-30 mg, depending upon weight) of D-MPH or MAS.
  
  
  RESULTS
  Doses of 10-20 mg of either D-MPH or MAS had little to no effect on hyperactivity-impulsivity and total ADHD symptom scores in subjects with the 9/9 genotype; this was in contrast to the dose-response curves of subjects with either the 10/10 or 10/9 genotype.
  
  
  CONCLUSIONS
  ADHD youth with the 9/9 genotype may require higher stimulant doses to achieve adequate symptom control.
authors.affiliation: 1 Department of Psychiatry and Behavioral Medicine, Seattle Children's Hospital, and University of Washington , Seattle, Washington.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Stein
authors.forename: Irwin
authors.initials: I
authors.lastname: Waldman
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Newcorn
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Bishop
authors.forename: Rick
authors.initials: R
authors.lastname: Kittles
authors.forename: Edwin H
authors.initials: EH
authors.lastname: Cook
mesh_terms: D000293:Adolescent; D000662:Amphetamines / Q000008:administration & dosage / Q000627:therapeutic use*; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000627:therapeutic use; D002648:Child; D018592:Cross-Over Studies; D064699:Dexmethylphenidate Hydrochloride / Q000627:therapeutic use*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male
chemical_list: D000662:Amphetamines; D000697:Central Nervous System Stimulants; D050483:Dopamine Plasma Membrane Transport Proteins; D064699:Dexmethylphenidate Hydrochloride