Association of norepinephrine transporter methylation with in vivo NET expression and hyperactivity-impulsivity symptoms in ADHD measured with PET.

Molecular Psychiatry
Helen L SigurdardottirRupert Lanzenberger

Abstract

Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder with a robust genetic influence. The norepinephrine transporter (NET) is of particular interest as it is one of the main targets in treatment of the disorder. As ADHD is a complex and polygenetic condition, the possible regulation by epigenetic processes has received increased attention. We sought to determine possible differences in NET promoter DNA methylation between patients with ADHD and healthy controls. DNA methylation levels in the promoter region of the NET were determined in 23 adult patients with ADHD and 23 healthy controls. A subgroup of 18 patients with ADHD and 18 healthy controls underwent positron emission tomography (PET) with the radioligand (S,S)-[18F]FMeNER-D2 to quantify the NET in several brain areas in vivo. Analyses revealed significant differences in NET methylation levels at several cytosine-phosphate-guanine (CpG) sites between groups. A defined segment of the NET promoter ("region 1") was hypermethylated in patients in comparison with controls. In ADHD patients, a negative correlation between methylation of a CpG site in this region and NET distribution in the thalamus, locus coeruleus, and the raphe nuclei was d...Continue Reading

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Citations

May 31, 2020·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Ottavia DipasqualeMara Cercignani
Nov 3, 2020·Neuropharmacology·Annika L WeißMarieke Klein
Nov 4, 2020·Proceedings of the National Academy of Sciences of the United States of America·Andrea BariSusumu Tonegawa

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Methods Mentioned

BETA
PCR
pharmacotherapy

Software Mentioned

EpiTYPER Analyser
ITER
FORE
PMOD
SPSS Statistics
Typer
EpiTYPER

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