Dataset Information

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

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.

SUBMITTER: Ziegler C

PROVIDER: S-EPMC4397412 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Ziegler Christiane C Dannlowski Udo U Bräuer David D Stevens Stephan S Laeger Inga I Wittmann Hannah H Kugel Harald H Dobel Christian C Hurlemann René R Reif Andreas A Lesch Klaus-Peter KP Heindel Walter W Kirschbaum Clemens C Arolt Volker V Gerlach Alexander L AL Hoyer Jürgen J Deckert Jürgen J Zwanzger Peter P Domschke Katharina K

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 20150107 6

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 ana ...[more]

PMID: 25563749

Similar Datasets

Project description:BACKGROUND:The neuropeptide Oxytocin (OXT) plays a central role in birthing, mother-infant bonding and a broad range of related social behaviours in mammals. More recently, interest has extended to epigenetic programming of genes involved in oxytocinergic neurotransmission. This review brings together early findings in a rapidly developing field of research, examining relationships between DNA methylation (DNAm) of the Oxytocin Receptor Gene (OXTR) and social and emotional behaviour in human populations. METHOD:A systematic search across Web of Knowledge/Science, Scopus, Medline and EMBASE captured all published studies prior to June 2017 examining the association between OXTR DNAm and human social and emotional outcomes. Search terms included 'oxytocin gene' or 'oxytocin receptor gene' and 'epigenetics' or 'DNA methylation'. Any article with a focus on social and emotional functioning was then identified from this set by manual review. RESULTS:Nineteen studies met eligibility criteria. There was considerable heterogeneity of study populations, tissue samples, instrumentation, measurement, and OXTR site foci. Only three studies examined functional consequences of OXTR DNAm on gene expression and protein synthesis. Increases in OXTR DNAm were associated with callous-unemotional traits in youth, social cognitive deficits in Autistic Spectrum Disorder (ASD), rigid thinking in anorexia nervosa, affect regulation problems, and problems with facial and emotional recognition. In contrast, reductions in DNAm were associated with perinatal stress, postnatal depression, social anxiety and autism in children. CONCLUSIONS:Consistent with an emerging field of inquiry, there is not yet sufficient evidence to draw conclusions about the role of OXTR DNAm in human social and emotional behaviour. However, taken together, findings point to increased OXTR DNAm in general impairments in social, cognitive and emotional functioning, and decreased OXTR DNAm in specific patterns of impairment related to mood and anxiety disorders (but not in all). Future progress in this field would be enhanced by adequately powered designs, greater phenotypic precision, and methodological improvements including longitudinal studies with multiple time-points to facilitate causal inference.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets