Research article summary (published 30 May 2009):

Dopamine transporter genotype and stimulant side effect factors in youth diagnosed with attention-deficit/hyperactivity disorder.

Full Abstract

The dopamine transporter locus (DAT1) has been studied as a risk factor for attention-deficit/hyperactivity disorder (ADHD) and in pharmacogenetic studies of stimulant response. Several prospective studies have reported an association between the homozygous 9 repeat allele of the DAT1 3' untranslated region (UTR) variable number tandem repeat (VNTR) (DAT1 3') and decreased efficacy of methylphenidate (MPH). We hypothesized that children with the 9/9 genotype would display higher rates of specific stimulant side effects. Data on adverse events and DAT1 3' genotypes were combined from two, double-blind, placebo-controlled, crossover studies of MPH conducted in child psychiatric outpatient clinics in Montreal and Washington, D.C. There were 177 participants, 5-16 years old (mean age = 8.99, standard deviation [SD] = 2), with ADHD. Parents completed the Stimulant Side Effect Scale (SERS) after a week of placebo and a week of MPH treatment. Principal components analysis of the SERS resulted in three factors: Emotionality, Somatic Complaints, and Over-focused. Children with the 9/9 genotype displayed higher scores on the Emotionality factor during placebo than children with the 9/10 and the 10/10 genotype, and their Emotionality scores increased further during MPH treatment (F[2,151] = 3.24, p < 0.05). Children with the 10/10 genotype displayed a significant increase in Somatic Complaint factor scores during MPH treatment relative to the other genotype groups (F[2,150] = 3.4, p < 0.05). These data provide suggestive evidence that DAT1 variants are differentially associated with specific stimulant side effects. Children with the 9/10 genotype displayed less severe stimulant side-effect ratings than either of the homozygous groups, who each displayed increased susceptibility to different types of adverse events. Preliminary evidence suggests that pharmacogenetic analysis using DAT1 variants shows promise for identifying individuals at increased or decreased risk for poor tolerability.

Author information

Author/s: Gruber, Reut (R); Joober, Ridha (R); Grizenko, Natalie (N); Leventhal, Bennett L (BL); Cook, Edwin H (EH); Stein, Mark A (MA);

Affiliation: Douglas Mental Health University Institute, Department of Psychiatry, McGill University, Montreal, Canada.

Grants: K24MHO1823 (Agency:PHS HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't

Journal: Journal of child and adolescent psychopharmacology (J Child Adolesc Psychopharmacol), published in United States. (Language: eng)

Reference: 2009-Jun; vol 19 (issue 3) : pp 233-9

Dates: Created 2009/06/12; Completed 2009/08/18;

PMID: 19519258, status: MEDLINE (last retrieved date: 8/21/2009)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MeSH Headings (categories) shown below.

Adolescent Attention Deficit Disorder with Hyperactivity - drug therapy; genetics Central Nervous System Stimulants - therapeutic use Child Child, Preschool Dopamine Plasma Membrane Transport Proteins - genetics Double-Blind Method Female Genotype

Genotype Humans Male Methylphenidate - adverse effects; therapeutic use Pharmacogenetics Principal Component Analysis Randomized Controlled Trials as Topic Risk Factors Severity of Illness Index

Note: Bold headings indicate primary MeSH headings or qualifiers.

Associated Chemicals: Central Nervous System Stimulants (0) ; Dopamine Plasma Membrane Transport Proteins (0) ; SLC6A3 protein, human (0) ; Methylphenidate (113-45-1)

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