Last week, we discussed the role of COMT in the treatment of ADHD. Today I would like to talk about another piece of the ADHD treatment puzzle: the ADRA2A receptor.
ADRA2A, short for alpha-2A-adrenergic receptor, is located abundantly in the prefrontal cortex of the brain. This receptor helps regulate norepinephrine (NE) which affects attention, focus, and impulse control. The ADRA2A receptor may play a role in both the development of ADHD and the effectiveness of ADHD medications. There are several genetic variations at ADRA2A: CC, CG, and GG.
Individuals carrying the GG variant, especially those 6-18 years old, have demonstrated the best response to methylphenidate. One study with 355 children and adolescents with ADHD showed that those with the GG allele were 69% more likely to have a response to methylphenidate compared to CC allele carriers. Alternatively, patients with the CC genetic variation at the ADRA2A receptor are predicted to have an unfavorable response to methylphenidate.
Therefore, we can predict patients with low COMT activity and the CC ADRA2A genetic variation will most likely have a poor response to methylphenidate, and those with high COMT activity and the GG variant at ADRA2A are predicted to have a favorable response to methylphenidate.
This is just another piece of the puzzle but may eliminate you or your child from wasting time and money on a medication that probably won’t be effective.
As always, consult your healthcare provider prior to making any medication changes.
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Sources:
Anderson, et al. (2015). Pharmacogenomics Applications to Patient Care (3rd ed., pp. 102-114). American College of Clinical Pharmacology.
"Management of ADHD with a Focus on PGx | Pharmacodynamic Genes", Genomind. February 3, 2021. https://genomindstag.wpengine.com/providers/management-of-adhd-with-a-focus-on-pharmacogenetics-pd-genes/
"Variant Annotations" PharmaGKB. (n.d.).https://www.pharmgkb.org/gene/PA35/variantAnnotation
Myer NM, Boland JR, Faraone SV. Pharmacogenetics predictors of methylphenidate efficacy in childhood ADHD. Mol Psychiatry. 2018 Sep;23(9):1929-1936. doi: 10.1038/mp.2017.234. Epub 2017 Dec 12. PMID: 29230023; PMCID: PMC7039663.
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