A Candidate Gene Analysis of Methylphenidate Response in Attention-Deficit/Hyperactivity Disorder

Autor/inn/en	McGough, James J.; McCracken, James T.; Loo, Sandra K.; Manganiello, Marc; Leung, Michael C.; Tietjens, Jeremy R.; Trinh, Thao; Baweja, Shilpa; Suddath, Robert; Smalley, Susan L.; Hellemann, Gerhard; Sugar, Catherine A.
Titel	A Candidate Gene Analysis of Methylphenidate Response in Attention-Deficit/Hyperactivity Disorder
Quelle	In: Journal of the American Academy of Child & Adolescent Psychiatry, 48 (2009) 12, S.1155-1164 (10 Seiten) PDF als Volltext Verfügbarkeit
Sprache	englisch
Dokumenttyp	gedruckt; online; Zeitschriftenaufsatz
ISSN	0890-8567
DOI	10.1097/CHI.0b013e3181bc72e3
Schlagwörter	Attention Deficit Hyperactivity Disorder; Mathematics Tests; Factor Analysis; Genetics; Laboratories; Children; Adolescents; Drug Therapy; Outcomes of Treatment; Influences; Science Education; Journal Articles; Evaluation Methods + Suchen Sie Ihr Suchwort? Faktorenanalyse; Humangenetik; Laboratory; Laboratorium; Child; Kind; Kinder; Adolescent; Adolescence; Adoleszenz; Jugend; Jugendalter; Jugendlicher; Influence; Einfluss; Einflussfaktor; Naturwissenschaftliche Bildung; Journal article; Zeitschriftenaufsatz
Abstract	Objective: This study examines the potential role of candidate genes in moderating treatment effects of methylphenidate (MPH) in attention-deficit/hyperactivity disorder (ADHD). Method: Eighty-two subjects with ADHD aged 6 to 17 years participated in a prospective, double-blind, placebo-controlled, multiple-dose, crossover titration trial of immediate release MPH three times daily. The subjects were assessed on a variety of parent and clinician ratings and a laboratory math test. Data reduction based on principal components analysis identified statistically derived efficacy and side effect outcomes. Results: Attention-deficit/hyperactivity disorder symptom response was predicted by polymorphisms at the serotonin transporter ("SLC6A4") intron 2 VNTR (p = 0.01), with a suggested trend for catechol-O-methyltransferase ("COMT") (p = 0.04). Gene x dose interactions were noted on math test outcomes for the dopamine D4 receptor ("DRD4") promoter (p = 0.008), "DRD4" exon 3 "VNTR" (p = 0.006), and "SLC6A4" promoter insertion/deletion polymorphism ("5HTTLPR") (p = 0.02). Irritability was predicted by COMT (p = 0.02). Vegetative symptoms were predicted by "5HTTLPR" (p = 0.003). No significant effects were noted for the dopamine transporter ("SLC6A3") or synaptosomal-associated protein 25 ("SNAP25"). Conclusions: This article confirms and expands previous studies suggesting that genes moderate ADHD treatment response. The ADHD outcomes are not unitary but reflect both behavioral and learning domains that are likely influenced by different genes. Future research should emphasize candidate gene and genome-wide association studies in larger samples, symptom reduction as well as side effects outcomes, and responses over full therapeutic dose ranges to assess differences in both gene and gene x dose interactive effects. (Contains 4 tables and 2 figures.) (As Provided).
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Erfasst von	ERIC (Education Resources Information Center), Washington, DC
Update	2017/4/10