Pharmacogenetics of methylphenidate response in preschoolers with ADHD

James McGough, James McCracken, James Swanson, Mark Riddle, Scott Kollins, Laurence Greenhill, Howard Abikoff, Mark Davies, Shirley Chuang, Tim Wigal, Sharon Wigal, Kelly Posner, Anne Skrobala, Elizabeth Kastelic, Jaswinder Ghuman, Charles Cunningham, Sharon Shigawa, Robert Moyzis, Benedetto Vitiello

Research output: Contribution to journalArticlepeer-review

96 Scopus citations


OBJECTIVE: The authors explored genetic moderators of symptom reduction and side effects in methylphenidate-treated preschool-age children diagnosed with attention-deficit/hyperactivity disorder (ADHD). METHOD: DNA was isolated from 81 subjects in a double-blind, placebo-controlled, crossover methylphenidate titration. Parents and teachers completed ADHD symptom scales and side effect ratings for each of five randomly administered weekly conditions that included immediate-release methylphenidate 1.25, 2.5, 5.0, 7.5 mg and placebo given three times daily. Candidate genes hypothesized to influence stimulant effects or individual risks for ADHD were genotyped. RESULTS: Although the primary analysis did not indicate significant genetic effects, secondary analyses revealed associations between symptom response and variants at the dopamine receptor (DRD4) promoter (p = .05) and synaptosomal-associated protein 25 (SNAP25) allelesT1065G (p = .03) andT1069C (p = .05). SNAP25 variants were also associated with tics (p = .02), buccal-lingual movements (p = .01), and irritability (p =.04). DRD4 variants were also associated with picking (p = .03). Increasing dose predicted irritability (p = .05) and social withdrawal (p = .03) with DRD4 variants. There were no significant effects for the dopamine transporter (DAT1). CONCLUSIONS: Emerging evidence suggests the potential for understanding the individual variability of response to and side effects of ADHD medications from the study of genetics, although additional research is required before these findings are proven to have clinical utility. Copyright 2006

Original languageEnglish (US)
Pages (from-to)1314-1322
Number of pages9
JournalJournal of the American Academy of Child and Adolescent Psychiatry
Issue number11
StatePublished - Nov 2006


  • Attention-deficit/hyperactivity disorder
  • Dopamine receptor (DRD4)
  • Methylphenidate
  • Pharmacogenetics
  • Synaptosomal-associated protein-25

ASJC Scopus subject areas

  • Developmental and Educational Psychology
  • Psychiatry and Mental health


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