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

The Pharmacogenomics Journal
M PagerolsJosep Antoni Ramos-Quiroga

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.

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Citations

Dec 22, 2017·Acta Pharmacologica Sinica·Dong-Dong ZhangXue-Han Zhang
Dec 13, 2017·Molecular Psychiatry·N M MyerS V Faraone
Apr 6, 2019·Pharmacogenetics and Genomics·Tyler StevensTeri E Klein
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Nov 12, 2019·Frontiers in Psychiatry·Patrick Vizeli, Matthias E Liechti
Feb 2, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Feng ChenYan Wang
Jun 27, 2021·Pharmacology & Therapeutics·Konstantin MechlerAlexander Häge

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