title: Neurocognitive effects of methylphenidate on ADHD children with different DAT genotypes: a longitudinal open label trial.
abstract: The variable number of tandem repeat polymorphism in the 3'-untranslated region of the dopamine transporter gene (DAT) may influence the variability of the therapeutic response to methylphenidate (MPH) in Attention Deficit/Hyperactivity Disorder (ADHD). For this reason we evaluated the neuropsychological functioning after a prolonged period of MPH treatment and after a specific time from MPH suspension. Relationship between DAT VNTR genotypes and neurocognitive response to MPH was analyzed in a sample of 108 drug-naive ADHD patients. The performance of children with ADHD on measures of working memory, inhibition and planning was assessed at 4, 8 and 24 weeks and at 8 weeks after MPH withdrawal. Patients with 9/9 genotype evidenced an improvement in response inhibition and working memory only at 4 weeks of treatment, in planning at 24 weeks of therapy and after 8 weeks of MPH suspension. Patients with 9/10 showed an improvement in response inhibition at 4, 8 and 24 weeks of treatment, in planning at 24 weeks and after 8 weeks of MPH suspension. Patients with 10/10 evidenced an improvement in response inhibition and working memory at 4, 8 and 24 weeks of treatment and in planning at 4, 8 and 24 weeks of treatment and after 8 weeks of suspension. These results indicate that the 9/9 ADHD genotype has a different response at 24 weeks treatment with MPH. 10/10 DAT allele seems to be associated with an increased expression level of the dopamine transporter and seems to mediate the MPH treatment response in ADHD patients.
authors.affiliation: Division of Child Neuropsychiatry, Department of Neuroscience, University of Rome Tor Vergata, Via Alberico 2 n.35, 00193 Rome, Italy. pasini@uniroma2.it
authors.forename: A
authors.initials: A
authors.lastname: Pasini
authors.forename: L
authors.initials: L
authors.lastname: Sinibaldi
authors.forename: C
authors.initials: C
authors.lastname: Paloscia
authors.forename: S
authors.initials: S
authors.lastname: Douzgou
authors.forename: M B
authors.initials: MB
authors.lastname: Pitzianti
authors.forename: E
authors.initials: E
authors.lastname: Romeo
authors.forename: P
authors.initials: P
authors.lastname: Curatolo
authors.forename: A
authors.initials: A
authors.lastname: Pizzuti
mesh_terms: D000293:Adolescent; D001289:Attention Deficit Disorder with Hyperactivity / Q000150:complications / Q000235:genetics*; D000697:Central Nervous System Stimulants / Q000627:therapeutic use*; D002648:Child; D003072:Cognition Disorders / Q000188:drug therapy* / Q000209:etiology / Q000235:genetics; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D007266:Inhibition, Psychological; D008137:Longitudinal Studies; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects; D008774:Methylphenidate / Q000627:therapeutic use*; D018598:Minisatellite Repeats / Q000235:genetics; D009483:Neuropsychological Tests; D010597:Pharmacogenetics; D011340:Problem Solving / Q000187:drug effects; D011569:Psychiatric Status Rating Scales; D013997:Time Factors
chemical_list: D000697:Central Nervous System Stimulants; D050483:Dopamine Plasma Membrane Transport Proteins; D008774:Methylphenidate