TY - JOUR
T1 - Pharmacogenetics of methylphenidate response in preschoolers with ADHD
AU - McGough, James
AU - McCracken, James
AU - Swanson, James
AU - Riddle, Mark
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
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
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U2 - 10.1097/01.chi.0000235083.40285.08
DO - 10.1097/01.chi.0000235083.40285.08
M3 - Article
C2 - 17023870
AN - SCOPUS:33750497630
SN - 0890-8567
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
IS - 11
ER -