Response to methylphenidate is not influenced by DAT1 polymorphisms in a sample of Brazilian adult patients with ADHD
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 probab…
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MPH activates HTR1A and DRD2 (and potentially other G-coupled receptors) that might have a reinforcing feedback role on MPH modulation of the NT imbalance through further regulation of DAT1.
“On the other hand, MPH activates HTR1A and DRD2 (and potentially other G-coupled receptors) that might have a reinforcing feedback role on MPH modulation of the NT imbalance through further regulation of DAT1 [174].”
From Molecular Characterisation of the Mechanism of Action of Stimulant Drugs Lisdexamfetamine and Methylphenidate on ADHD Neurobiology: A Review (2022) · cites this paper as [174]
The role of MPH as an inhibitor of DAT1 and 5-HT1A leads to inhibition of circadian clock regulators CRY1 and CRY2.
“It is interesting to note that the role of MPH as an inhibitor of DAT1 [174] and 5-HT1A [141] leads to inhibition of circadian clock regulators CRY1 and CRY2.”
From Molecular Characterisation of the Mechanism of Action of Stimulant Drugs Lisdexamfetamine and Methylphenidate on ADHD Neurobiology: A Review (2022) · cites this paper as [174]
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The genetics of attention deficit/hyperactivity disorder in adults, a review
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“On the other hand, MPH activates HTR1A and DRD2 (and potentially other G-coupled receptors) that might have a reinforcing feedback role on MPH modulation of the NT imbalance through further regulation of DAT1 [174].”
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Self-citation
- Authors
- Contini, V., Victor, M. M., Marques, F. Z. C., Bertuzzi, G. P., Salgado, C. A. I., Silva, K. L., Sousa, N. O., Grevet, E. H., Belmonte-de-Abreu, P., & Bau, C. H. D.
- Affiliations
- Universidade Federal do Rio Grande do Sul (BR)
- Hospital de Clínicas de Porto Alegre (BR)
- The University of Sydney (AU)
- Corresponding author
- Bau, Claiton H. D.
- ORCID
- Venue
- Journal of Neural Transmission
- Published
- 2010-01-05
- Volume
- 117
- Issue
- 2
- Pages
- 269-276
- ISSN
- 0300-9564 (ISSN-L)
- 1435-1463
- OpenAlex
- W2032201343
- Cited by
- 27
- References
- 9
- Citations by year
- 2024: 1 · 2023: 1 · 2022: 4 · 2019: 1 · 2018: 2 · 2017: 2 · 2016: 2 · 2015: 1 · 2014: 3 · 2013: 2 · 2012: 3
- FWCI
- 2.19
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Journal of Neural Transmission (publishedVersion)
- PubMed (publishedVersion)
- FedUni ResearchOnline (Federation University Australia) (submittedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Keywords
- attention deficit hyperactivity disorder, methylphenidate response, dopamine transporter gene, DAT1 polymorphism, pharmacogenetics, haplotypes, adult ADHD, Brazilian patients
- MeSH terms
- Adult, Attention Deficit Disorder with Hyperactivity, Brazil, Female, Genotype, Haplotypes, Humans, Male, Methylphenidate, Polymorphism, Genetic, Psychiatric Status Rating Scales, Treatment Outcome, Dopamine Uptake Inhibitors, 3' Untranslated Regions, Dopamine Plasma Membrane Transport Proteins
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