title: Pharmacogenetics of methylphenidate response in preschoolers with ADHD.
abstract: 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).
  
  
  METHODS
  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.
authors.affiliation: Drs. McGough and McCracken and Ms. Shigawa are with the UCLA Semel Institute for Neuroscience and Human Behavior, Los Angeles; Drs. Swanson, T. Wigal, and S. Wigal are with the University of California, Irvine; Drs. Greenhill and Posner, Mr. Davies (retired), Ms. Chuang, and Ms. Skrobala are with New York State Psychiatric Institute, Columbia University, New York; Drs. Riddle and Kastelic are with Johns Hopkins University, Baltimore; Dr. Kollins is with Duke University Medical Center, Durham, NC; Dr. Abikoff is with the New York University Child Study Center, New York; Dr. Ghuman is with the University of Arizona, Tucson; Dr. Cunningham is with the McMaster University, Hamilton, Ontario, Canada; Dr. Moyzis is with the University of California, Irvine; and Dr. Vitiello is with the National Institute of Mental Health, Bethesda, MD.. Electronic address: jmcgough@mednet.ucla.edu.
authors.forename: James
authors.initials: J
authors.lastname: McGOUGH
authors.affiliation: Drs. McGough and McCracken and Ms. Shigawa are with the UCLA Semel Institute for Neuroscience and Human Behavior, Los Angeles; Drs. Swanson, T. Wigal, and S. Wigal are with the University of California, Irvine; Drs. Greenhill and Posner, Mr. Davies (retired), Ms. Chuang, and Ms. Skrobala are with New York State Psychiatric Institute, Columbia University, New York; Drs. Riddle and Kastelic are with Johns Hopkins University, Baltimore; Dr. Kollins is with Duke University Medical Center, Durham, NC; Dr. Abikoff is with the New York University Child Study Center, New York; Dr. Ghuman is with the University of Arizona, Tucson; Dr. Cunningham is with the McMaster University, Hamilton, Ontario, Canada; Dr. Moyzis is with the University of California, Irvine; and Dr. Vitiello is with the National Institute of Mental Health, Bethesda, MD.
authors.forename: James
authors.initials: J
authors.lastname: McCRACKEN
authors.affiliation: Drs. McGough and McCracken and Ms. Shigawa are with the UCLA Semel Institute for Neuroscience and Human Behavior, Los Angeles; Drs. Swanson, T. Wigal, and S. Wigal are with the University of California, Irvine; Drs. Greenhill and Posner, Mr. Davies (retired), Ms. Chuang, and Ms. Skrobala are with New York State Psychiatric Institute, Columbia University, New York; Drs. Riddle and Kastelic are with Johns Hopkins University, Baltimore; Dr. Kollins is with Duke University Medical Center, Durham, NC; Dr. Abikoff is with the New York University Child Study Center, New York; Dr. Ghuman is with the University of Arizona, Tucson; Dr. Cunningham is with the McMaster University, Hamilton, Ontario, Canada; Dr. Moyzis is with the University of California, Irvine; and Dr. Vitiello is with the National Institute of Mental Health, Bethesda, MD.
authors.forename: James
authors.initials: J
authors.lastname: Swanson
authors.affiliation: Drs. McGough and McCracken and Ms. Shigawa are with the UCLA Semel Institute for Neuroscience and Human Behavior, Los Angeles; Drs. Swanson, T. Wigal, and S. Wigal are with the University of California, Irvine; Drs. Greenhill and Posner, Mr. Davies (retired), Ms. Chuang, and Ms. Skrobala are with New York State Psychiatric Institute, Columbia University, New York; Drs. Riddle and Kastelic are with Johns Hopkins University, Baltimore; Dr. Kollins is with Duke University Medical Center, Durham, NC; Dr. Abikoff is with the New York University Child Study Center, New York; Dr. Ghuman is with the University of Arizona, Tucson; Dr. Cunningham is with the McMaster University, Hamilton, Ontario, Canada; Dr. Moyzis is with the University of California, Irvine; and Dr. Vitiello is with the National Institute of Mental Health, Bethesda, MD.
authors.forename: Mark
authors.initials: M
authors.lastname: Riddle
authors.affiliation: Drs. McGough and McCracken and Ms. Shigawa are with the UCLA Semel Institute for Neuroscience and Human Behavior, Los Angeles; Drs. Swanson, T. Wigal, and S. Wigal are with the University of California, Irvine; Drs. Greenhill and Posner, Mr. Davies (retired), Ms. Chuang, and Ms. Skrobala are with New York State Psychiatric Institute, Columbia University, New York; Drs. Riddle and Kastelic are with Johns Hopkins University, Baltimore; Dr. Kollins is with Duke University Medical Center, Durham, NC; Dr. Abikoff is with the New York University Child Study Center, New York; Dr. Ghuman is with the University of Arizona, Tucson; Dr. Cunningham is with the McMaster University, Hamilton, Ontario, Canada; Dr. Moyzis is with the University of California, Irvine; and Dr. Vitiello is with the National Institute of Mental Health, Bethesda, MD.
authors.forename: Scott
authors.initials: S
authors.lastname: Kollins
authors.affiliation: Drs. McGough and McCracken and Ms. Shigawa are with the UCLA Semel Institute for Neuroscience and Human Behavior, Los Angeles; Drs. Swanson, T. Wigal, and S. Wigal are with the University of California, Irvine; Drs. Greenhill and Posner, Mr. Davies (retired), Ms. Chuang, and Ms. Skrobala are with New York State Psychiatric Institute, Columbia University, New York; Drs. Riddle and Kastelic are with Johns Hopkins University, Baltimore; Dr. Kollins is with Duke University Medical Center, Durham, NC; Dr. Abikoff is with the New York University Child Study Center, New York; Dr. Ghuman is with the University of Arizona, Tucson; Dr. Cunningham is with the McMaster University, Hamilton, Ontario, Canada; Dr. Moyzis is with the University of California, Irvine; and Dr. Vitiello is with the National Institute of Mental Health, Bethesda, MD.
authors.forename: Laurence
authors.initials: L
authors.lastname: Greenhill
authors.affiliation: Drs. McGough and McCracken and Ms. Shigawa are with the UCLA Semel Institute for Neuroscience and Human Behavior, Los Angeles; Drs. Swanson, T. Wigal, and S. Wigal are with the University of California, Irvine; Drs. Greenhill and Posner, Mr. Davies (retired), Ms. Chuang, and Ms. Skrobala are with New York State Psychiatric Institute, Columbia University, New York; Drs. Riddle and Kastelic are with Johns Hopkins University, Baltimore; Dr. Kollins is with Duke University Medical Center, Durham, NC; Dr. Abikoff is with the New York University Child Study Center, New York; Dr. Ghuman is with the University of Arizona, Tucson; Dr. Cunningham is with the McMaster University, Hamilton, Ontario, Canada; Dr. Moyzis is with the University of California, Irvine; and Dr. Vitiello is with the National Institute of Mental Health, Bethesda, MD.
authors.forename: Howard
authors.initials: H
authors.lastname: Abikoff
authors.affiliation: Drs. McGough and McCracken and Ms. Shigawa are with the UCLA Semel Institute for Neuroscience and Human Behavior, Los Angeles; Drs. Swanson, T. Wigal, and S. Wigal are with the University of California, Irvine; Drs. Greenhill and Posner, Mr. Davies (retired), Ms. Chuang, and Ms. Skrobala are with New York State Psychiatric Institute, Columbia University, New York; Drs. Riddle and Kastelic are with Johns Hopkins University, Baltimore; Dr. Kollins is with Duke University Medical Center, Durham, NC; Dr. Abikoff is with the New York University Child Study Center, New York; Dr. Ghuman is with the University of Arizona, Tucson; Dr. Cunningham is with the McMaster University, Hamilton, Ontario, Canada; Dr. Moyzis is with the University of California, Irvine; and Dr. Vitiello is with the National Institute of Mental Health, Bethesda, MD.
authors.forename: Mark
authors.initials: M
authors.lastname: Davies
authors.affiliation: Drs. McGough and McCracken and Ms. Shigawa are with the UCLA Semel Institute for Neuroscience and Human Behavior, Los Angeles; Drs. Swanson, T. Wigal, and S. Wigal are with the University of California, Irvine; Drs. Greenhill and Posner, Mr. Davies (retired), Ms. Chuang, and Ms. Skrobala are with New York State Psychiatric Institute, Columbia University, New York; Drs. Riddle and Kastelic are with Johns Hopkins University, Baltimore; Dr. Kollins is with Duke University Medical Center, Durham, NC; Dr. Abikoff is with the New York University Child Study Center, New York; Dr. Ghuman is with the University of Arizona, Tucson; Dr. Cunningham is with the McMaster University, Hamilton, Ontario, Canada; Dr. Moyzis is with the University of California, Irvine; and Dr. Vitiello is with the National Institute of Mental Health, Bethesda, MD.
authors.forename: Shirley
authors.initials: S
authors.lastname: Chuang
authors.affiliation: Drs. McGough and McCracken and Ms. Shigawa are with the UCLA Semel Institute for Neuroscience and Human Behavior, Los Angeles; Drs. Swanson, T. Wigal, and S. Wigal are with the University of California, Irvine; Drs. Greenhill and Posner, Mr. Davies (retired), Ms. Chuang, and Ms. Skrobala are with New York State Psychiatric Institute, Columbia University, New York; Drs. Riddle and Kastelic are with Johns Hopkins University, Baltimore; Dr. Kollins is with Duke University Medical Center, Durham, NC; Dr. Abikoff is with the New York University Child Study Center, New York; Dr. Ghuman is with the University of Arizona, Tucson; Dr. Cunningham is with the McMaster University, Hamilton, Ontario, Canada; Dr. Moyzis is with the University of California, Irvine; and Dr. Vitiello is with the National Institute of Mental Health, Bethesda, MD.
authors.forename: Tim
authors.initials: T
authors.lastname: Wigal
authors.affiliation: Drs. McGough and McCracken and Ms. Shigawa are with the UCLA Semel Institute for Neuroscience and Human Behavior, Los Angeles; Drs. Swanson, T. Wigal, and S. Wigal are with the University of California, Irvine; Drs. Greenhill and Posner, Mr. Davies (retired), Ms. Chuang, and Ms. Skrobala are with New York State Psychiatric Institute, Columbia University, New York; Drs. Riddle and Kastelic are with Johns Hopkins University, Baltimore; Dr. Kollins is with Duke University Medical Center, Durham, NC; Dr. Abikoff is with the New York University Child Study Center, New York; Dr. Ghuman is with the University of Arizona, Tucson; Dr. Cunningham is with the McMaster University, Hamilton, Ontario, Canada; Dr. Moyzis is with the University of California, Irvine; and Dr. Vitiello is with the National Institute of Mental Health, Bethesda, MD.
authors.forename: Sharon
authors.initials: S
authors.lastname: Wigal
authors.affiliation: Drs. McGough and McCracken and Ms. Shigawa are with the UCLA Semel Institute for Neuroscience and Human Behavior, Los Angeles; Drs. Swanson, T. Wigal, and S. Wigal are with the University of California, Irvine; Drs. Greenhill and Posner, Mr. Davies (retired), Ms. Chuang, and Ms. Skrobala are with New York State Psychiatric Institute, Columbia University, New York; Drs. Riddle and Kastelic are with Johns Hopkins University, Baltimore; Dr. Kollins is with Duke University Medical Center, Durham, NC; Dr. Abikoff is with the New York University Child Study Center, New York; Dr. Ghuman is with the University of Arizona, Tucson; Dr. Cunningham is with the McMaster University, Hamilton, Ontario, Canada; Dr. Moyzis is with the University of California, Irvine; and Dr. Vitiello is with the National Institute of Mental Health, Bethesda, MD.
authors.forename: Kelly
authors.initials: K
authors.lastname: Posner
authors.affiliation: Drs. McGough and McCracken and Ms. Shigawa are with the UCLA Semel Institute for Neuroscience and Human Behavior, Los Angeles; Drs. Swanson, T. Wigal, and S. Wigal are with the University of California, Irvine; Drs. Greenhill and Posner, Mr. Davies (retired), Ms. Chuang, and Ms. Skrobala are with New York State Psychiatric Institute, Columbia University, New York; Drs. Riddle and Kastelic are with Johns Hopkins University, Baltimore; Dr. Kollins is with Duke University Medical Center, Durham, NC; Dr. Abikoff is with the New York University Child Study Center, New York; Dr. Ghuman is with the University of Arizona, Tucson; Dr. Cunningham is with the McMaster University, Hamilton, Ontario, Canada; Dr. Moyzis is with the University of California, Irvine; and Dr. Vitiello is with the National Institute of Mental Health, Bethesda, MD.
authors.forename: Anne
authors.initials: A
authors.lastname: Skrobala
authors.affiliation: Drs. McGough and McCracken and Ms. Shigawa are with the UCLA Semel Institute for Neuroscience and Human Behavior, Los Angeles; Drs. Swanson, T. Wigal, and S. Wigal are with the University of California, Irvine; Drs. Greenhill and Posner, Mr. Davies (retired), Ms. Chuang, and Ms. Skrobala are with New York State Psychiatric Institute, Columbia University, New York; Drs. Riddle and Kastelic are with Johns Hopkins University, Baltimore; Dr. Kollins is with Duke University Medical Center, Durham, NC; Dr. Abikoff is with the New York University Child Study Center, New York; Dr. Ghuman is with the University of Arizona, Tucson; Dr. Cunningham is with the McMaster University, Hamilton, Ontario, Canada; Dr. Moyzis is with the University of California, Irvine; and Dr. Vitiello is with the National Institute of Mental Health, Bethesda, MD.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Kastelic
authors.affiliation: Drs. McGough and McCracken and Ms. Shigawa are with the UCLA Semel Institute for Neuroscience and Human Behavior, Los Angeles; Drs. Swanson, T. Wigal, and S. Wigal are with the University of California, Irvine; Drs. Greenhill and Posner, Mr. Davies (retired), Ms. Chuang, and Ms. Skrobala are with New York State Psychiatric Institute, Columbia University, New York; Drs. Riddle and Kastelic are with Johns Hopkins University, Baltimore; Dr. Kollins is with Duke University Medical Center, Durham, NC; Dr. Abikoff is with the New York University Child Study Center, New York; Dr. Ghuman is with the University of Arizona, Tucson; Dr. Cunningham is with the McMaster University, Hamilton, Ontario, Canada; Dr. Moyzis is with the University of California, Irvine; and Dr. Vitiello is with the National Institute of Mental Health, Bethesda, MD.
authors.forename: Jaswinder
authors.initials: J
authors.lastname: Ghuman
authors.affiliation: Drs. McGough and McCracken and Ms. Shigawa are with the UCLA Semel Institute for Neuroscience and Human Behavior, Los Angeles; Drs. Swanson, T. Wigal, and S. Wigal are with the University of California, Irvine; Drs. Greenhill and Posner, Mr. Davies (retired), Ms. Chuang, and Ms. Skrobala are with New York State Psychiatric Institute, Columbia University, New York; Drs. Riddle and Kastelic are with Johns Hopkins University, Baltimore; Dr. Kollins is with Duke University Medical Center, Durham, NC; Dr. Abikoff is with the New York University Child Study Center, New York; Dr. Ghuman is with the University of Arizona, Tucson; Dr. Cunningham is with the McMaster University, Hamilton, Ontario, Canada; Dr. Moyzis is with the University of California, Irvine; and Dr. Vitiello is with the National Institute of Mental Health, Bethesda, MD.
authors.forename: Charles
authors.initials: C
authors.lastname: Cunningham
authors.affiliation: Drs. McGough and McCracken and Ms. Shigawa are with the UCLA Semel Institute for Neuroscience and Human Behavior, Los Angeles; Drs. Swanson, T. Wigal, and S. Wigal are with the University of California, Irvine; Drs. Greenhill and Posner, Mr. Davies (retired), Ms. Chuang, and Ms. Skrobala are with New York State Psychiatric Institute, Columbia University, New York; Drs. Riddle and Kastelic are with Johns Hopkins University, Baltimore; Dr. Kollins is with Duke University Medical Center, Durham, NC; Dr. Abikoff is with the New York University Child Study Center, New York; Dr. Ghuman is with the University of Arizona, Tucson; Dr. Cunningham is with the McMaster University, Hamilton, Ontario, Canada; Dr. Moyzis is with the University of California, Irvine; and Dr. Vitiello is with the National Institute of Mental Health, Bethesda, MD.
authors.forename: Sharon
authors.initials: S
authors.lastname: Shigawa
authors.affiliation: Drs. McGough and McCracken and Ms. Shigawa are with the UCLA Semel Institute for Neuroscience and Human Behavior, Los Angeles; Drs. Swanson, T. Wigal, and S. Wigal are with the University of California, Irvine; Drs. Greenhill and Posner, Mr. Davies (retired), Ms. Chuang, and Ms. Skrobala are with New York State Psychiatric Institute, Columbia University, New York; Drs. Riddle and Kastelic are with Johns Hopkins University, Baltimore; Dr. Kollins is with Duke University Medical Center, Durham, NC; Dr. Abikoff is with the New York University Child Study Center, New York; Dr. Ghuman is with the University of Arizona, Tucson; Dr. Cunningham is with the McMaster University, Hamilton, Ontario, Canada; Dr. Moyzis is with the University of California, Irvine; and Dr. Vitiello is with the National Institute of Mental Health, Bethesda, MD.
authors.forename: Robert
authors.initials: R
authors.lastname: Moyzis
authors.affiliation: Drs. McGough and McCracken and Ms. Shigawa are with the UCLA Semel Institute for Neuroscience and Human Behavior, Los Angeles; Drs. Swanson, T. Wigal, and S. Wigal are with the University of California, Irvine; Drs. Greenhill and Posner, Mr. Davies (retired), Ms. Chuang, and Ms. Skrobala are with New York State Psychiatric Institute, Columbia University, New York; Drs. Riddle and Kastelic are with Johns Hopkins University, Baltimore; Dr. Kollins is with Duke University Medical Center, Durham, NC; Dr. Abikoff is with the New York University Child Study Center, New York; Dr. Ghuman is with the University of Arizona, Tucson; Dr. Cunningham is with the McMaster University, Hamilton, Ontario, Canada; Dr. Moyzis is with the University of California, Irvine; and Dr. Vitiello is with the National Institute of Mental Health, Bethesda, MD.
authors.forename: Benedetto
authors.initials: B
authors.lastname: Vitiello
mesh_terms: D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy* / Q000235:genetics*; D000697:Central Nervous System Stimulants / Q000009:adverse effects / Q000627:therapeutic use*; D002675:Child, Preschool; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007508:Irritable Mood / Q000187:drug effects; D008297:Male; D008774:Methylphenidate / Q000009:adverse effects / Q000627:therapeutic use*; D010597:Pharmacogenetics; D016133:Polymerase Chain Reaction; D050638:Receptors, Dopamine D4 / Q000235:genetics; D012934:Social Isolation; D050825:Synaptosomal-Associated Protein 25 / Q000235:genetics; D020323:Tics / Q000139:chemically induced
chemical_list: D000697:Central Nervous System Stimulants; D050825:Synaptosomal-Associated Protein 25; D050638:Receptors, Dopamine D4; D008774:Methylphenidate