Pharmacogenetics of methylphenidate response in preschoolers with ADHD

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

Research output: Contribution to journalArticle

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). 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
Volume45
Issue number11
DOIs
StatePublished - Nov 2006

Fingerprint

Methylphenidate
Pharmacogenetics
Attention Deficit Disorder with Hyperactivity
Synaptosomal-Associated Protein 25
Placebos
Tics
Dopamine Plasma Membrane Transport Proteins
Cheek
Dopamine Receptors
Preschool Children
Tongue
Parents
DNA
Research
Genes

Keywords

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

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Developmental and Educational Psychology

Cite this

Pharmacogenetics of methylphenidate response in preschoolers with ADHD. / McGough, James; McCracken, James; Swanson, James; Riddle, Mark A; Kollins, Scott; Greenhill, Laurence; Abikoff, Howard; Davies, Mark; Chuang, Shirley; Wigal, Tim; Wigal, Sharon; Posner, Kelly; Skrobala, Anne; Kastelic, Elizabeth A; Ghuman, Jaswinder; Cunningham, Charles; Shigawa, Sharon; Moyzis, Robert; Vitiello, Benedetto.

In: Journal of the American Academy of Child and Adolescent Psychiatry, Vol. 45, No. 11, 11.2006, p. 1314-1322.

Research output: Contribution to journalArticle

McGough, J, McCracken, J, Swanson, J, Riddle, MA, Kollins, S, Greenhill, L, Abikoff, H, Davies, M, Chuang, S, Wigal, T, Wigal, S, Posner, K, Skrobala, A, Kastelic, EA, Ghuman, J, Cunningham, C, Shigawa, S, Moyzis, R & Vitiello, B 2006, 'Pharmacogenetics of methylphenidate response in preschoolers with ADHD', Journal of the American Academy of Child and Adolescent Psychiatry, vol. 45, no. 11, pp. 1314-1322. https://doi.org/10.1097/01.chi.0000235083.40285.08
McGough, James ; McCracken, James ; Swanson, James ; Riddle, Mark A ; Kollins, Scott ; Greenhill, Laurence ; Abikoff, Howard ; Davies, Mark ; Chuang, Shirley ; Wigal, Tim ; Wigal, Sharon ; Posner, Kelly ; Skrobala, Anne ; Kastelic, Elizabeth A ; Ghuman, Jaswinder ; Cunningham, Charles ; Shigawa, Sharon ; Moyzis, Robert ; Vitiello, Benedetto. / Pharmacogenetics of methylphenidate response in preschoolers with ADHD. In: Journal of the American Academy of Child and Adolescent Psychiatry. 2006 ; Vol. 45, No. 11. pp. 1314-1322.
@article{1fe60fb389d648bf93d3969774ad4992,
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). 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",
keywords = "Attention-deficit/hyperactivity disorder, Dopamine receptor (DRD4), Methylphenidate, Pharmacogenetics, Synaptosomal-associated protein-25",
author = "James McGough and James McCracken and James Swanson and Riddle, {Mark A} and Scott Kollins and Laurence Greenhill and Howard Abikoff and Mark Davies and Shirley Chuang and Tim Wigal and Sharon Wigal and Kelly Posner and Anne Skrobala and Kastelic, {Elizabeth A} and Jaswinder Ghuman and Charles Cunningham and Sharon Shigawa and Robert Moyzis and Benedetto Vitiello",
year = "2006",
month = "11",
doi = "10.1097/01.chi.0000235083.40285.08",
language = "English (US)",
volume = "45",
pages = "1314--1322",
journal = "Journal of the American Academy of Child and Adolescent Psychiatry",
issn = "0890-8567",
publisher = "Elsevier Limited",
number = "11",

}

TY - JOUR

T1 - Pharmacogenetics of methylphenidate response in preschoolers with ADHD

AU - McGough, James

AU - McCracken, James

AU - Swanson, James

AU - Riddle, Mark A

AU - Kollins, Scott

AU - Greenhill, Laurence

AU - Abikoff, Howard

AU - Davies, Mark

AU - Chuang, Shirley

AU - Wigal, Tim

AU - Wigal, Sharon

AU - Posner, Kelly

AU - Skrobala, Anne

AU - Kastelic, Elizabeth A

AU - Ghuman, Jaswinder

AU - Cunningham, Charles

AU - Shigawa, Sharon

AU - Moyzis, Robert

AU - Vitiello, Benedetto

PY - 2006/11

Y1 - 2006/11

N2 - 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

AB - 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

KW - Attention-deficit/hyperactivity disorder

KW - Dopamine receptor (DRD4)

KW - Methylphenidate

KW - Pharmacogenetics

KW - Synaptosomal-associated protein-25

UR - http://www.scopus.com/inward/record.url?scp=33750497630&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33750497630&partnerID=8YFLogxK

U2 - 10.1097/01.chi.0000235083.40285.08

DO - 10.1097/01.chi.0000235083.40285.08

M3 - Article

VL - 45

SP - 1314

EP - 1322

JO - Journal of the American Academy of Child and Adolescent Psychiatry

JF - Journal of the American Academy of Child and Adolescent Psychiatry

SN - 0890-8567

IS - 11

ER -