Dopamine Transporter 3′-UTR VNTR Genotype and ADHD: a Pharmaco-Behavioural Genetic Study with Methylphenidate

• Published in: Neuropsychopharmacology (New York, N.Y.) Vol. 32; no. 6; pp. 1370 - 1376
• Main Authors: Joober, Ridha, Grizenko, Natalie, Sengupta, Sarojini, Amor, Leila Ben, Schmitz, Norbert, Schwartz, George, Karama, Sherif, Lageix, Philippe, Fathalli, Ferid, Torkaman-Zehi, Adam, Stepanian, Marina Ter
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.06.2007; Nature Publishing; Nature Publishing Group
• Subjects: 3' Untranslated Regions - genetics; Attention Deficit Disorder with Hyperactivity - drug therapy; Attention Deficit Disorder with Hyperactivity - genetics; Attention Deficit Disorder with Hyperactivity - psychology; Attention deficit hyperactivity disorder; Behavior; Behavioral Sciences; Biological and medical sciences; Biological Psychology; Central Nervous System Stimulants - administration & dosage; Central Nervous System Stimulants - therapeutic use; Child; Child & adolescent psychiatry; Cross-Over Studies; Dopamine; Dopamine Plasma Membrane Transport Proteins - genetics; Female; Genotype; Genotype & phenotype; Humans; Hypotheses; Male; Medical sciences; Medicine; Medicine & Public Health; Methylphenidate - administration & dosage; Methylphenidate - therapeutic use; Minisatellite Repeats - genetics; Neuropharmacology; Neurosciences; original-article; Pharmacology. Drug treatments; Pharmacotherapy; Polymorphism; Polymorphism, Genetic - genetics; Prospective Studies; Psychiatric Status Rating Scales; Psychiatry; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Research centers; Schools; Canada; Montreal Quebec Canada; methylphenidate; dopamine transporter; attention-deficit; hyperactivity disorder; pharmacogenetics; dopamine transporter SLC6A3; Pharmacogenetics; CNS stimulant; Hyperactivity; Psychotropic; Genotype; Attentional disorder; Piperidine derivatives; Genetics; Attention disorder with hyperactivity; Behavior; Methylphenidate
• ISSN: 0893-133X; 1740-634X
• DOI: 10.1038/sj.npp.1301240

We sought to test the hypothesis that the variable number of tandem repeat (VNTR) polymorphism in the 3′-untranslated region (3′-UTR) of the SLC6A3 gene modulates behavior in children with ADHD and/or behavioral response to methylphenidate (MPH). One hundred and fifty-nine children with AHDH (6–12 years) were assessed with regard to the Conners’ Global Index for parents (CGI-Parents) and teachers (CGI-Teachers) and the response of these behaviors to MPH (0.5 mg/kg/day) using a 2-week prospective within-subject (crossover) trial. Based on CGI-Parents, the profile of behavioral response to MPH as compared to placebo was not parallel in the three groups of children separated according to their genotype in the 3′-UTR VNTR polymorphism of SLC6A3, as indicated by a significant ( p =0.017) genotype by treatment two-way interaction. Individuals having the 9/10 and 10/10 genotypes displayed a significant positive response to MPH as opposed to those homozygous for the 9-repeat allele. No genotype or genotype by treatment interaction was observed for CGI-Teachers. These findings support a role for the DAT gene 3′-UTR VNTR polymorphism in modulating the response of some behavioral dimensions to MPH in children with ADHD. They also suggest the presence of genetic heterogeneity that could be indexed by the quality of behavioral response to MPH.