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Pharmacogenomics J. 2017 Jan;17(1):98-104. doi: 10.1038/tpj.2015.89. Epub 2016 Jan 26.

Pharmacogenetics of methylphenidate response and tolerability in attention-deficit/hyperactivity disorder.

Author information

1
Psychiatric Genetics Unit, Vall d'Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain.
2
Department of Psychiatry, Hospital Universitari Vall d'Hebron, Barcelona, Spain.
3
Biomedical Network Research Centre on Mental Health (CIBERSAM), Barcelona, Spain.
4
Departament de Genètica, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain.
5
Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Barcelona, Spain.
6
Institut de Biomedicina de la Universitat de Barcelona (IBUB), Barcelona, Spain.
7
Department of Psychiatry and Legal Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain.

Abstract

Methylphenidate (MPH) is the most frequently used pharmacological treatment in children with attention-deficit/hyperactivity disorder. However, a considerable interindividual variability exists in clinical outcome, which may reflect underlying genetic influences. We analyzed 57 single-nucleotide polymorphisms in 9 dopamine-related candidate genes (TH, DBH, COMT, DAT1 and DRD1-5) as potential predictors of MPH efficacy and tolerability, and we considered prenatal and perinatal risk factors as environmental hazards that may influence treatment effects in a gene-by-environment analysis. Our results provide evidence for the contribution of DRD3 (P=0.041; odds ratio (OR)=4.00), DBH (P=0.032; OR=2.85), TH (P=5.5e-03; OR=4.34) and prenatal smoking (P=1.7e-03; OR=5.10) to the clinical efficacy of MPH, with a higher risk for treatment failure in genetically susceptible subjects whose mother smoked during pregnancy. Adverse events after MPH treatment were significantly associated with variation in DBH (P=6.4e-03; OR=0.28) and DRD2 (P=0.047; OR=3.76). This study suggests that the dopaminergic system together with prenatal smoking exposure may moderate MPH treatment effects.

PMID:
26810137
DOI:
10.1038/tpj.2015.89
[Indexed for MEDLINE]

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