Pharmacogenetics of Methylphenidate Response in Preschoolers with ADHD

Autor/inn/en	McGough, James; McCracken, James; Swanson, James; Riddle, Mark; Kollins, Scott; Greenhill, Laurence; Abikoff, Howard; Davies, Mark; Chuang, Shirley; Wigal, Tim; Wigal, Sharon; Posner, Kelly; Skrobala, Anne; Kastelic, Elizabeth; Ghuman, Jaswinder; Cunningham, Charles; Shigawa, Sharon; Moyzis, Robert; Vitiello, Benedetto
Titel	Pharmacogenetics of Methylphenidate Response in Preschoolers with ADHD
Quelle	In: Journal of the American Academy of Child and Adolescent Psychiatry, 45 (2006) 11, S.1314-1322 (9 Seiten) PDF als Volltext Verfügbarkeit
Sprache	englisch
Dokumenttyp	gedruckt; online; Zeitschriftenaufsatz
ISSN	0890-8567
Schlagwörter	Hyperactivity; Genetics; Attention Deficit Disorders; Drug Therapy; Pharmacology; Preschool Children; Outcomes of Treatment; Symptoms (Individual Disorders); Correlation + Suchen Sie Ihr Suchwort? Hyperaktivität; Humangenetik; Attention deficit hyperactivity disorder; ADHS; Aufmerksamkeits-Defizit-Hyperaktivitäts-Störung; Aufmerksamkeitsstörung; Arzneikunde; Pre-school age; Preschool age; Child; Children; Pre-school education; Preschool education; Vorschulalter; Kind; Kinder; Vorschulkind; Vorschulkinder; Vorschulerziehung; Vorschule; Psychiatrische Symptomatik; Korrelation
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 = 0.05) and synaptosomal-associated protein 25 (SNAP25) alleles T1065G (p = 0.03) and T1069C (p = 0.05). SNAP25 variants were also associated with tics (p= 0.02), buccallingual movements (p = 0.01), and irritability (p = 0.04). DRD4 variants were also associated with picking (p = 0.03). Increasing dose predicted irritability (p = 0.05) and social withdrawal (p = 0.03) 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. (Contains 4 tables.) (Author).
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Erfasst von	ERIC (Education Resources Information Center), Washington, DC
Update	2017/4/10