In:
PLOS ONE, Public Library of Science (PLoS), Vol. 18, No. 4 ( 2023-4-27), p. e0282813-
Kurzfassung:
Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder that often persists into adulthood. Core symptoms of ADHD, such as impulsivity, are caused by an interaction of genetic and environmental factors. Epigenetic modifications of DNA, such as DNA methylation, are thought to mediate the interplay of these factors. Tryptophan hydroxylase 2 (TPH2) is the rate-limiting enzyme in brain serotonin synthesis. The TPH2 gene has frequently been investigated in relation to ADHD, e.g., showing that TPH2 G-703T (rs4570625) polymorphism influences response control and prefrontal signaling in ADHD patients. In this (epi)genetic imaging study we examined 144 children and adolescents (74 patients, 14 females) using fMRI at rest and during performing a waiting impulsivity (WI) paradigm. Both, TPH2 G-703T (rs4570625) genotype and DNA methylation in the 5’ untranslated region (5’UTR) of TPH2 were associated with wavelet variance in fronto-parietal regions and behavioral performance, taking TPH2 genotype into account. In detail, comparisons between genotypes of patients and controls revealed highest wavelet variance and longest reaction times in patients carrying the T allele [indicative for a gene-dosage effect, i.e., the WI phenotype is a direct result of the cumulative effect of ADHD and TPH2 variation]. Regressions revealed a significant effect on one specific DNA methylation site in ADHD patients but not controls, in terms of a significant prediction of wavelet variance in fronto-parietal regions as well as premature responses. By the example of the TPH2 G-703T (rs4570625) polymorphism, we provide insight into how interactive genetic and DNA methylation affect the ADHD and/or impulsive endophenotype.
Materialart:
Online-Ressource
ISSN:
1932-6203
DOI:
10.1371/journal.pone.0282813
DOI:
10.1371/journal.pone.0282813.g001
DOI:
10.1371/journal.pone.0282813.g002
DOI:
10.1371/journal.pone.0282813.g003
DOI:
10.1371/journal.pone.0282813.t001
DOI:
10.1371/journal.pone.0282813.t002
DOI:
10.1371/journal.pone.0282813.t003
DOI:
10.1371/journal.pone.0282813.t004
DOI:
10.1371/journal.pone.0282813.s001
DOI:
10.1371/journal.pone.0282813.s002
DOI:
10.1371/journal.pone.0282813.s003
DOI:
10.1371/journal.pone.0282813.s004
DOI:
10.1371/journal.pone.0282813.s005
DOI:
10.1371/journal.pone.0282813.s006
DOI:
10.1371/journal.pone.0282813.s007
DOI:
10.1371/journal.pone.0282813.s008
DOI:
10.1371/journal.pone.0282813.s009
DOI:
10.1371/journal.pone.0282813.s010
Sprache:
Englisch
Verlag:
Public Library of Science (PLoS)
Publikationsdatum:
2023
ZDB Id:
2267670-3