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Association of response to methylphenidate in adults with ADHD with a polymorphism in SLC6A3 (DAT1)

Published online by Cambridge University Press:  16 April 2020

J.S. Kooij
Affiliation:
Programme Adult ADHD, PsyQ, The Hague, The Netherlands
A.M. Boonstra
Affiliation:
Department of Psychology, Erasmus University, Rotterdam, The Netherlands
S.H. Vermeulen
Affiliation:
Department of Antropogenetica, University Medical Center St. Radboud, Nijmegen, The Netherlands
J.A. Heister
Affiliation:
Department of Antropogenetica, University Medical Center St. Radboud, Nijmegen, The Netherlands
H. Burger
Affiliation:
Department of Epidemiology and Department of Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
J.K. Buitelaar
Affiliation:
Department of Psychiatry, Radboud University, Nijmegen, The Netherlands
B. Franke
Affiliation:
Department of Antropogenetica, University Medical Center St. Radboud, Nijmegen, The Netherlands

Abstract

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Background

During this presentation, the first pharmacogenetic study on response to methylphenidate (MPH) in adults with ADHD will be reported.

Methods

We performed a stratified analysis of the association between response to MPH, assessed under double-blind conditions, in 42 adults with ADHD, and polymorphisms in the genes encoding the dopamine transporter, SLC6A3 (DAT1), the norepinephrine transporter, SLC6A2 (NET), and the dopamine receptor D4, DRD4.

Results

Polymorphisms in the DRD4 and the SLC6A2 (NET) genes were not significantly associated with the response to MPH treatment; however, the VNTR polymorphism in the 3'untranslated region of SLC6A3 (DAT1) was significantly associated with an increased likelihood of a response to MPH treatment (odds ratio 5.4; 95% CI 1.4-21.9) in heterozygous 10-repeat allele carriers in comparison with the 10/10 homozygotes: 52.2% of the participants heterozygous for the 10-repeat allele improved significantly on MPH treatment whereas only 22.2% of the 10/10 homozygous individuals did.

Conclusions

This study confirms that the SLC6A3 (DAT1) genotype may have an influential role in determining the response to MPH in the treatment of ADHD. The SLC6A3 (DAT1) gene might be a factor worth evaluating further in the future regarding choice of treatment and possibly dose adjustment.

Type
S41. Symposium: Genes, Endophenotypes and Treatment of Adult ADHD
Copyright
Copyright © European Psychiatric Association 2007
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