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Neuropsychopharmacology. 2015 May;40(6):1528-38. doi: 10.1038/npp.2015.2. Epub 2015 Jan 7.

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

Author information

1
Department of Psychiatry, University of Würzburg, Würzburg, Germany.
2
1] Department of Psychiatry, University of Münster, Münster, Germany [2] Department of Psychiatry, University of Marburg, Marburg, Germany.
3
Institute of Clinical Psychology and Psychotherapy, Technische Universität Dresden, Dresden, Germany.
4
Institute of Clinical Psychology and Psychotherapy, University of Cologne, Cologne, Germany.
5
1] Department of Psychiatry, University of Münster, Münster, Germany [2] Institute of Psychology, University of Münster, Münster, Germany.
6
Department of Psychiatry, University of Münster, Münster, Germany.
7
Department of Clinical Radiology, University of Münster, Münster, Germany.
8
Institute of Biogmagnetism and Biosignal Analysis, University of Münster, Münster, Germany.
9
Division of Medical Psychology, Department of Psychiatry, University of Bonn, Bonn, Germany.
10
Division of Molecular Psychiatry, Department of Psychiatry, University of Würzburg, Würzburg, Germany.
11
Institute of Biopsychology, Technische Universität Dresden, Dresden, Germany.
12
1] Department of Psychiatry, University of Münster, Münster, Germany [2] kbo-Inn-Salzach-Klinikum, Wasserburg am Inn, Germany.

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.

PMID:
25563749
PMCID:
PMC4397412
DOI:
10.1038/npp.2015.2
[Indexed for MEDLINE]
Free PMC Article

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