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Response to methylphenidate is not influenced by DAT1 polymorphisms in a sample of Brazilian adult patients with ADHD

  • Biological Child and Adolescent Psychiatry - Original Article
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Abstract

Several lines of evidence suggest a relevant role for the dopamine transporter (DAT1) gene not only as a susceptibility factor for attention-deficit hyperactivity disorder (ADHD), but also as a predictor of individual methylphenidate (MPH) response. Pharmacogenetic studies of MPH response in ADHD have mainly focused on the 40-bp variable number of tandem repeats (VNTR) in the 3′ untranslated region (3′-UTR) of DAT1. Most studies were performed in samples of children and conflicting findings were obtained. Only two studies have assessed 3′-VNTR in samples of adults—one with positive and the other with negative findings. In the present study, we investigate three potentially relevant polymorphisms in DAT1 gene (−839 C > T; Int8 VNTR and 3′-VNTR), and their possible role in therapeutic response to MPH treatment in a sample of 171 Brazilian adults with ADHD. The diagnostic procedures followed the DSM-IV criteria and the outcome measures were the scales Swanson, Nolan, and Pelham Rating scale version IV and the Clinical Global Impression-Severity Scale, applied at the beginning and after the 30th day of treatment. Drug response was assessed by both categorical and dimensional approaches. There was no effect of any DAT1 polymorphisms or haplotypes on MPH response. This is the second report demonstrating absence of differences in MPH response according to DAT1 genotypes in adults with ADHD. Although DAT protein is crucial for the effect of MPH, genetic variations in DAT1 gene probably do not have a significant clinical role in this sample of adults with ADHD.

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Acknowledgment

Thanks are due to Rafael G. Karam, Felipe A. Picon, Paula O. G. da Silva, Gregory D. Zeni, and Eduardo Vitola for helping in sample collection of ADHD patients, and to Camila R. Consiglio and Felipe A. Sassi for being part of the laboratory analysis. CNPq—Instituto do Milênio, FIPE-HCPA, FAPERGS, DECIT/SCTIE/MS/PPSUS, and PRONEX funded this study.

Conflict of interest statement

The ADHD Program received educational and research support from the following pharmaceutical companies in the last 3 years: Abbott, Bristol-Myers Squibb, Eli-Lilly, Janssen-Cilag, and Novartis. Dr Belmonte-de-Abreu is in the speaker’s bureau or is a consultant for Janssen-Cilag and Bristol-Myers Squibb. Dr Grevet is in the speaker’s bureau or is a consultant for Novartis and Janssen-Cilag.

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Authors and Affiliations

  1. Departament of Genetics, Instituto de Biociências, Universidade Federal do Rio Grande do Sul, Caixa Postal:15053, Porto Alegre, RS, 91501-970, Brazil

    Verônica Contini, Guilherme P. Bertuzzi & Claiton H. D. Bau

  2. Adult ADHD Outpatient Clinic, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil

    Marcelo M. Victor, Carlos A. I. Salgado, Katiane L. Silva, Nyvia O. Sousa, Eugenio H. Grevet, Paulo Belmonte-de-Abreu & Claiton H. D. Bau

  3. Basic and Clinical Genomics Laboratory, School of Medical Sciences and Bosch Institute, The University of Sydney, Sydney, NSW, Australia

    Francine Z. C. Marques

  4. Departament of Psychiatry, Faculdade de Medicina, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil

    Paulo Belmonte-de-Abreu

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  1. Verônica Contini
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  2. Marcelo M. Victor
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  8. Eugenio H. Grevet
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  10. Claiton H. D. Bau
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Contini, V., Victor, M.M., Marques, F.Z.C. et al. Response to methylphenidate is not influenced by DAT1 polymorphisms in a sample of Brazilian adult patients with ADHD. J Neural Transm 117, 269–276 (2010). https://doi.org/10.1007/s00702-009-0362-2

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