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Cited by 91Attention Deficit Hyperactivity DisorderPharmacogenetics and Drug MetabolismNeurotransmitter Receptor Influence on Behavior

Pharmacogenetics predictors of methylphenidate efficacy in childhood ADHD

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Myer, N M, Boland, J R, Faraone, S V·2018·Molecular Psychiatry
DOI 10.1038/mp.2017.234PMC PMC7039663
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Abstract

Stimulant medication has long been effective in treating attention-deficit/hyperactivity disorder (ADHD) and is currently the first-line pharmacological treatment for children. Both methylphenidate and amphetamine modulate extracellular catecholamine levels through interaction with dopaminergic, adrenergic and serotonergic system components; it is therefore likely that catecholaminergic molecular components influence the effects of ADHD treatment. Using meta-analysis, we sought to identify predictors of pharmacotherapy to further the clinical implementation of personalized medicine. We identified 36 studies (3647 children) linking the effectiveness of methylphenidate treatment with DNA variants. Pooled-data revealed a statistically significant association between single nucleotide polymorphisms (SNPs) rs1800544 ADRA2A (odds ratio: 1.69; confidence interval: 1.12-2.55), rs4680 COMT (odds ratio (OR): 1.40; confidence interval: 1.04-1.87), rs5569 SLC6A2 (odds ratio: 1.73; confidence interval: 1.26-2.37) and rs28386840 SLC6A2 (odds ratio: 2.93; confidence interval: 1.76-4.90), and, repeat variants variable number tandem repeat (VNTR) 4 DRD4 (odds ratio: 1.66; confidence interval: 1.16-2.37) and VNTR 10 SLC6A3 (odds ratio: 0.74; confidence interval: 0.60-0.90), whereas the following variants were not statistically significant: rs1947274 LPHN3 (odds ratio: 0.95; confidence interval: 0.71-1.26), rs5661665 LPHN3 (odds ratio: 1.07; confidence interval: 0.84-1.37) and VNTR 7 DRD4 (odds ratio: 0.68; confidence interval: 0.47-1.00). Funnel plot asymmetry among SLC6A3 studies was identified and attributed largely to small study effects. Egger's regression test and Duval and Tweedie's 'trim and fill' were used to examine and correct for publication bias. These findings have major implications for advancing our therapeutic approach to childhood ADHD treatment.

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Authors
Myer, N. M., Boland, J. R., & Faraone, S. V.
Affiliations
SUNY Upstate Medical University (US)
Corresponding author
Myer, N M
ORCID
Venue
Molecular Psychiatry
Publisher
Springer Science and Business Media LLC
Published
2017-12-12
Volume
23
Issue
9
Pages
1929-1936
ISSN
  • 1359-4184 (ISSN-L)
  • 1476-5578
DOI
10.1038/mp.2017.234
PMC
PMC7039663
OpenAlex
W2772773692
Cited by
91
References
14
Citations by year
2026: 11 · 2025: 7 · 2024: 9 · 2023: 10 · 2022: 15 · 2021: 14 · 2020: 9 · 2019: 9 · 2018: 7
FWCI
5.62
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Molecular Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Sunovion
  • National Institute of Mental Health (U01MH109536, R01MH101519)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Keywords
methylphenidate, attention deficit hyperactivity disorder, childhood ADHD, pharmacogenetics, treatment response prediction, single nucleotide polymorphisms, ADRA2A, catechol-O-methyltransferase, norepinephrine transporter, dopamine transporter, DRD4, LPHN3, catecholamine transporters, dopamine receptors, personalized medicine, stimulant medication response, publication bias
MeSH terms
Attention Deficit Disorder with Hyperactivity, Catechol O-Methyltransferase, Child, Female, Genotype, Humans, Male, Methylphenidate, Pharmacogenetics, Treatment Outcome, Receptors, Adrenergic, alpha-2, Minisatellite Repeats, Polymorphism, Single Nucleotide, Dopamine Plasma Membrane Transport Proteins, Norepinephrine Plasma Membrane Transport Proteins, Receptors, Dopamine D4, Biomarkers, Pharmacological

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