Evidence map›Paper›PMID 25563749›Full record

ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2015

Oxytocin receptor gene methylation: converging multilevel evidence for a role in social anxiety.

Christiane Ziegler, Udo Dannlowski, David Bräuer, Stephan Stevens, Inga Laeger, Hannah Wittmann, Harald Kugel, Christian Dobel, René Hurlemann, Andreas Reif and 9 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
87citing papers in PubMed, 4 pooled it
31.4field-weighted citation impact, top 1% 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

87 citing papers in PubMed, 4 syntheses or guidelines pooled it, 188 citations in OpenAlex.

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  11. Acute stress induces changes in epigenome-wide DNA methylation.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026
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27 more citing papers are in PubMed but not listed here.

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

19 authors at 6 institutions in 1 country.

Christiane ZieglerDepartment of Psychiatry, University of Würzburg, Würzburg, Germany.
Udo Dannlowski1] Department of Psychiatry, University of Münster, Münster, Germany [2] Department of Psychiatry, University of Marburg, Marburg, Germany.
David BräuerInstitute of Clinical Psychology and Psychotherapy, Technische Universität Dresden, Dresden, Germany.
Stephan StevensInstitute of Clinical Psychology and Psychotherapy, University of Cologne, Cologne, Germany.
Inga Laeger1] Department of Psychiatry, University of Münster, Münster, Germany [2] Institute of Psychology, University of Münster, Münster, Germany.
Hannah WittmannDepartment of Psychiatry, University of Münster, Münster, Germany.
Harald KugelDepartment of Clinical Radiology, University of Münster, Münster, Germany.
Christian DobelInstitute of Biogmagnetism and Biosignal Analysis, University of Münster, Münster, Germany.
René HurlemannDivision of Medical Psychology, Department of Psychiatry, University of Bonn, Bonn, Germany.
Andreas ReifDepartment of Psychiatry, University of Würzburg, Würzburg, Germany.
Klaus-Peter LeschDivision of Molecular Psychiatry, Department of Psychiatry, University of Würzburg, Würzburg, Germany.
Walter HeindelDepartment of Clinical Radiology, University of Münster, Münster, Germany.
Clemens KirschbaumInstitute of Biopsychology, Technische Universität Dresden, Dresden, Germany.
Volker AroltDepartment of Psychiatry, University of Münster, Münster, Germany.
Alexander L GerlachInstitute of Clinical Psychology and Psychotherapy, University of Cologne, Cologne, Germany.
Jürgen HoyerInstitute of Clinical Psychology and Psychotherapy, Technische Universität Dresden, Dresden, Germany.
Jürgen DeckertDepartment of Psychiatry, University of Würzburg, Würzburg, Germany.
Peter Zwanzger1] Department of Psychiatry, University of Münster, Münster, Germany [2] kbo-Inn-Salzach-Klinikum, Wasserburg am Inn, Germany.
Katharina DomschkeDepartment of Psychiatry, University of Würzburg, Würzburg, Germany.
University of Münster · DEUniversity of Würzburg · DETU Dresden · DEUniversity of Cologne · DEInn-Salzach-Klinikum · DEUniversity of Bonn · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Social anxiety disorder (SAD) is a commonly occurring and highly disabling disorder. The neuropeptide oxytocin and its receptor (OXTR) have been implicated in social cognition and behavior. This study-for the first time applying a multilevel epigenetic approach-investigates the role of OXTR gene methylation in categorical, dimensional, and intermediate neuroendocrinological/neural network phenotypes of social anxiety. A total of 110 unmedicated patients with SAD and matched 110 controls were analyzed for OXTR methylation by direct sequencing of sodium bisulfite-converted DNA extracted from whole blood. Furthermore, OXTR methylation was investigated regarding SAD-related traits (Social Phobia Scale (SPS) and Social Interaction Anxiety Scale (SIAS)), salivary cortisol response during the Trier social stress test (TSST), and amygdala responsiveness to social phobia related verbal stimuli using fMRI. Significantly decreased OXTR methylation particularly at CpG Chr3: 8 809 437 was associated with (1) the categorical phenotype of SAD (p<0.001, Cohen's d=0.535), (2) increased SPS and SIAS scores (p<0.001), (3) increased cortisol response to the TSST (p=0.02), and (4) increased amygdala responsiveness during social phobia-related word processing (right: p(corr)<0.001; left: p(corr)=0.005). Assuming that decreased OXTR methylation confers increased OXTR expression, the present finding may reflect a compensatory upregulation for pathologically reduced oxytocin levels or a causally relevant increased OXTR activation in SAD and related traits. OXTR methylation patterns might thus serve as peripheral surrogates of oxytocin tone and aid in establishing accessible biomarkers of SAD risk allowing for indicated preventive interventions and personalized treatment approaches targeting the oxytocin system.

Indexed as

DNA MethylationSocial BehaviorAdultAmygdalaAnxiety DisordersFemaleGenetic VariationHumansHydrocortisoneMagnetic Resonance ImagingMaleNeuropsychological TestsPsychiatric Status Rating ScalesReceptors, OxytocinSalivaHydrocortisoneOXTR protein, humanReceptors, Oxytocin

Identifiers

PMID25563749
PMCPMC4397412
OpenAlexW2104323563

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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 OpenQuestion graph.