Research article summary (published 30 Jan 2007):

Association of the adrenergic alpha2A receptor gene with methylphenidate improvement of inattentive symptoms in children and adolescents with attention-deficit/hyperactivity disorder.

Full Abstract

CONTEXT: Preclinical studies have demonstrated the relevance of adrenergic alpha2A receptor on the attentional process and the mechanism of action of methylphenidate hydrochloride. Several molecular genetic investigations suggest a role for the adrenergic alpha2A receptor gene (ADRA2A) in attention-deficit/hyperactivity disorder (ADHD), especially in the inattentive dimension. However, the effect of ADRA2A in the response to methylphenidate in humans has not been previously investigated, to our knowledge. OBJECTIVE: To evaluate the association between the ADRA2A -1291 C>G polymorphism and the clinical response to methylphenidate treatment in children and adolescents with ADHD. DESIGN: A pharmacogenomic study was undertaken between November 1, 2002, and May 1, 2004, using a nonrandom assignment, quasi-experimental design. SETTING: An ADHD outpatient program at a university hospital in Brazil. Patients One hundred six patients consecutively diagnosed as having ADHD were genotyped for the ADRA2A -1291 C>G polymorphism and were included in the analyses. Intervention Short-acting methylphenidate administered in increasing dosages until no further clinical improvement was detected or until limited adverse effects occurred. MAIN OUTCOME MEASURES: The primary outcome measure was the parent-rated inattentive subscale of the Swanson, Nolan, and Pelham Scale version IV. Secondary outcome measures included the Barkley Side Effect Rating Scale and the parent-rated hyperactivity-impulsivity subscale of the Swanson, Nolan, and Pelham Scale version IV. Scales were applied by child psychiatrists blinded to genotype at baseline and at 1 and 3 months of treatment. RESULTS: A significant interaction effect between the presence of the G allele and treatment with methylphenidate over time on inattentive scores was detected during the 3 months of treatment (n = 106; F(2,198) = 4.30; P = .02). CONCLUSIONS: We documented the effect of the G allele at the ADRA2A -1291 C>G polymorphism on the improvement of inattentive symptoms with methylphenidate treatment in children and adolescents with ADHD. Our findings provide clinical evidence for the involvement of the noradrenergic system in the modulation of methylphenidate action.

Author information

Author/s: Polanczyk, Guilherme (G); Zeni, Cristian (C); Genro, Julia P (JP); Guimarães, Ana P (AP); Roman, Tatiana (T); Hutz, Mara H (MH); Rohde, Luis A (LA);

Affiliation: Attention-Deficit/Hyperactivity Disorder Outpatient Clinic, Child and Adolescent Psychiatric Division, Hospital de Clínicas de Porto Alegre, Federal University of Rio Grande do Sul, Brazil.

Journal and publication information

Publication Type: Clinical Trial; Comparative Study; Journal Article; Research Support, Non-U.S. Gov't

Journal: Archives of general psychiatry (Arch Gen Psychiatry), published in United States. (Language: eng)

Reference: 2007-Feb; vol 64 (issue 2) : pp 218-24

Dates: Created 2007/02/06; Completed 2007/04/16;

PMID: 17283289, status: MEDLINE (last retrieval date: 2/18/2009, IMS Date: )

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 shown below.

Adolescent Ambulatory Care Attention - drug effects Attention Deficit Disorder with Hyperactivity - drug therapy; epidemiology; genetics Brazil - epidemiology Central Nervous System Stimulants - adverse effects; pharmacology; therapeutic use Child Chromosomes, Human, Pair 10 - genetics Female

Genotype Humans Male Methylphenidate - adverse effects; pharmacology; therapeutic use Pedigree Pharmacogenetics Polymorphism, Single Nucleotide Receptors, Adrenergic, alpha-2 - genetics Treatment Outcome

Associated Chemicals: Central Nervous System Stimulants (0) ; Receptors, Adrenergic, alpha-2 (0) ; receptor, adrenergic, alpha-2A (0) ; Methylphenidate (113-45-1)

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