Evidence map›Paper›PMID 37104367›Full record

ArticlePloS one2023

Serotonergic modulation of normal and abnormal brain dynamics: The genetic influence of the TPH2 G-703T genotype and DNA methylation on wavelet variance in children and adolescents with and without ADHD.

Atae Akhrif, Marcel Romanos, Katharina Peters, Ann-Kathrin Furtmann, Julian Caspers, Klaus-Peter Lesch, Eva M Meisenzahl-Lechner, Susanne Neufang

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
2.2field-weighted citation impact, top 13% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed, 10 citations in OpenAlex.

  1. Trial
  2. Article
  3. [The microbiota-gut-brain axis in childhood attention-deficit/hyperactivity disorder: mechanisms and therapeutic advances].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2025
    Review
  4. Review
  5. Serotonin dysfunction in ADHD.Journal of neurodevelopmental disorders · 2025
    Review
  6. Article
  7. Review
  8. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 2 countries.

Atae AkhrifDepartment of Psychiatry and Psychotherapy, Medical Faculty, Heinrich-Heine-University Duesseldorf, Duesseldorf, Germany.
Marcel RomanosDepartment of Child and Adolescent Psychiatry, Center of Mental Health, University Hospital Wuerzburg, Wuerzburg, Germany.
Katharina PetersDepartment of Child and Adolescent Psychiatry, Center of Mental Health, University Hospital Wuerzburg, Wuerzburg, Germany.
Ann-Kathrin FurtmannDepartment of Psychiatry and Psychotherapy, Medical Faculty, Heinrich-Heine-University Duesseldorf, Duesseldorf, Germany.
Julian CaspersDepartment of Diagnostic and Interventional Radiology, Medical Faculty, Heinrich-Heine-University Duesseldorf, Duesseldorf, Germany.
Klaus-Peter LeschDivision of Molecular Psychiatry, Center of Mental Health, University of Wuerzburg, Wuerzburg, Germany.
Eva M Meisenzahl-LechnerDepartment of Psychiatry and Psychotherapy, Medical Faculty, Heinrich-Heine-University Duesseldorf, Duesseldorf, Germany.
Susanne NeufangDepartment of Psychiatry and Psychotherapy, Medical Faculty, Heinrich-Heine-University Duesseldorf, Duesseldorf, Germany.ORCID 0000-0002-4927-2969
Heinrich Heine University Düsseldorf · DEMaastricht University · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

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.

Indexed as

Attention Deficit Disorder with HyperactivityBrainDNA MethylationFemaleGenotypeHumansPolymorphism, Single NucleotideTryptophan HydroxylaseTryptophan OxygenaseTPH2 protein, humanTryptophan HydroxylaseTryptophan Oxygenase

Identifiers

PMID37104367
PMCPMC10138254
OpenAlexW4367175218

What Socratic holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.