Oxytocin response to an experimental psychosocial challenge in adults exposed to traumatic experiences during childhood or adolescence

Pierrehumbert, Blaise; Torrisi, Raffaella; Laufer, Dominique; Halfon, Olivier; Ansermet, François; Popović, Maja

doi:10.1016/j.neuroscience.2009.12.016

Cited by 116 publications

(85 citation statements)

References 79 publications

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“…These results are in keeping with reports of a negative relationship between endogenous oxytocin and salivary cortisol levels during the TSST (Pierrehumbert et al, 2010) and of intranasal oxytocin administration attenuating the stress-induced cortisol response to the TSST in healthy subjects receiving social support (Heinrichs et al, 2003).…”

Section: Discussionsupporting

confidence: 91%

Oxytocin Receptor Gene Methylation: Converging Multilevel Evidence for a Role in Social Anxiety

Ziegler

Dannlowski

Bräuer

et al. 2015

Neuropsychopharmacol

159

100

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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 approachinvestigates 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 (po0.001, Cohen's d ¼ 0.535), (2) increased SPS and SIAS scores (po0.001), (3) increased cortisol response to the TSST (p ¼ 0.02), and (4) increased amygdala responsiveness during social phobia-related word processing (right: p corr o0.001; left: p corr ¼ 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.

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Section: Discussionsupporting

confidence: 91%

Oxytocin Receptor Gene Methylation: Converging Multilevel Evidence for a Role in Social Anxiety

Ziegler

Dannlowski

Bräuer

et al. 2015

Neuropsychopharmacol

159

100

View full text Add to dashboard Cite

show abstract

“…This one study supports a beneficial effect of daily OXT administration in GAD patients over 3 weeks, especially in male subjects (80). In the context of human anxiety, the majority of studies have been performed in volunteers in variants of the Trier Social Stress Test, which, on the whole, revealed that acute intranasal OXT reduces anxiety symptoms (82)(83)(84)(85)(86). However, it is clear that further studies assessing the effect of chronic or repeated OXT administration, and in GAD patients, are warranted.…”

Section: Oxt and General Anxiety: Human Researchsupporting

confidence: 59%

Oxytocin in General Anxiety and Social Fear: A Translational Approach

Neumann

Slattery

2016

Biological Psychiatry

384

293

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The neuropeptide oxytocin (OXT) has been revealed as a profound anxiolytic and antistress factor of the brain, besides its many prosocial and reproductive effects. Therefore, there is substantial scientific and medical interest in its potential therapeutic use for the treatment of psychopathologies associated with anxiety, fear, and social dysfunctions, such as generalized anxiety disorder, posttraumatic stress disorder, and social anxiety disorder, as well as autism and schizophrenia, among others. Focusing on preclinical studies, we review the existing evidence for the regulatory capacity of OXT to fine-tune general and social anxiety-related behaviors, as well as cued and social fear conditioning from a translational perspective. The available evidence from animal and human studies substantiates the hypothesis of an imbalance of the endogenous brain OXT system in the etiology of anxiety disorders, particularly those with a social component such as social anxiety disorder. In addition, such an imbalance of the OXT system is also likely to be the consequence of chronic OXT treatment resulting in a dose-dependent reduction in OXT receptor availability and increased anxiety.

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“…In adult male rats exposed to a stressor on three successive days, peak plasma levels of post-stress OT were lower on day 2 and 3 than day 1 (Wotjak et al, 1998). In a human study, adults who endured sexual abuse early in life had somewhat lower levels of OT than those without this history of abuse following an acute experimental stressor (though cancer survivors exposed to this experimental stressor had higher levels of OT; Pierrehumbert et al, 2010). Thus, additional studies of OT and current stress in those with a history of adversity may help to account for past discrepant findings.…”

Section: Introductionmentioning

confidence: 92%

“…For instance, researchers have proposed that early adversity may impact oxytocin receptor (OTR) gene methylation (Bakermans-Kranenburg & van IJzendoorn, 2013), and animal studies have linked early adversity (in the form of less maternal care) to decreased OTR levels (Francis et al, 2000;Francis, Young, Meaney, & Insel, 2002;Pedersen & Boccia, 2002). In contrast, other human studies have found higher levels of plasma or salivary OT in adults who endured adversity early in life in the form of maltreatment or cancer (Bhandari et al, 2014;Pierrehumbert et al, 2010). Although methodological differences between studies (e.g.…”

Section: Introductionmentioning

confidence: 99%

“…Indeed, it has been suggested that an individual's history of stressful experiences may play a role in the OT stress response (Pierrehumbert et al, 2010). One possibility is that OT may be released in response to stress in individuals without a history of adversity, increasing endogenous OT levels and serving anxiolytic and stress-reducing functions.…”

Section: Introductionmentioning

confidence: 99%

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Attachment security and recent stressful life events predict oxytocin levels: a pilot study of pregnant women with high levels of cumulative psychosocial adversity

Samuel

Hayton

Gold

et al. 2015

Attachment & Human Development

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Lower OT levels were found among those who were insecurely attached, and among those who experienced SLE within the last year. In a multiple linear regression, both attachment security and SLE significantly contributed to a model of prenatal OT levels. These individual difference factors explained 38% of the variance in prenatal OT, which may in turn predict poorer maternal mental health and caregiving outcomes during the postpartum period.

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Oxytocin response to an experimental psychosocial challenge in adults exposed to traumatic experiences during childhood or adolescence

Cited by 116 publications

References 79 publications

Oxytocin Receptor Gene Methylation: Converging Multilevel Evidence for a Role in Social Anxiety

Oxytocin Receptor Gene Methylation: Converging Multilevel Evidence for a Role in Social Anxiety

Oxytocin in General Anxiety and Social Fear: A Translational Approach

Attachment security and recent stressful life events predict oxytocin levels: a pilot study of pregnant women with high levels of cumulative psychosocial adversity

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