Intranasal oxytocin enhances stress-protective effects of social support in women with negative childhood experiences during a virtual Trier Social Stress Test

Riem, Madelon M E; Kunst, Laura E.; Bekker, Marrie H. J.; Fallon, Monica; Kupper, Nina

doi:10.1016/j.psyneuen.2019.104482

Cited by 40 publications

(22 citation statements)

References 52 publications

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“…First, physical distancing and lack of direct social interactions due to social isolation have adverse effects on the activity of the OXT system: social isolation results in lower density of neuronal branching (Neumann and Grinevich, unpublished), and reduced neuropeptide synthesis, and prevents socially stimulated central OXT release [66,191,192]. Second, social support is an important factor for our mental and physical well-being and for the recovery from any disease [193,194], and these effects are at least partly mediated by the OXT system [195][196][197][198] (for review see [39]). Finally, due to the pro-social and anti-stress effects of the brain OXT system, IN application of the synthetic peptide or efficient activation of the endogenous OXT are potential options to prevent or reverse social isolation-induced impairment in mental well-being and the development of serious psychopathologies, associated with such a dramatic crisis affecting our social lives.…”

Section: The Oxt System In Times Of the Covid-19 Crisismentioning

confidence: 99%

Brain oxytocin: how puzzle stones from animal studies translate into psychiatry

2020

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The neuropeptide oxytocin has attracted great attention of the general public, basic neuroscience researchers, psychologists, and psychiatrists due to its profound pro-social, anxiolytic, and "anti-stress" behavioral and physiological effects, and its potential application for treatment of mental diseases associated with altered socio-emotional competence. During the last decade, substantial progress has been achieved in understanding the complex neurobiology of the oxytocin system, including oxytocinergic pathways, local release patterns, and oxytocin receptor distribution in the brain, as well as intraneuronal oxytocin receptor signaling. However, the picture of oxytocin actions remains far from being complete, and the central question remains: "How does a single neuropeptide exert such pleotropic actions?" Although this phenomenon, typical for many of about 100 identified neuropeptides, may emerge from the anatomical divergence of oxytocin neurons, their multiple central projections, distinct oxytocin-sensitive cell types in different brain regions, and multiple intraneuronal signaling pathways determining the specific cellular response, further basic studies are required. In conjunction, numerous reports on positive effects of intranasal application of oxytocin on human brain networks controlling socio-emotional behavior in health and disease require harmonic tandems of basic researchers and clinicians. During the COVID-19 crisis in 2020, oxytocin research seems central as question of social isolation-induced inactivation of the oxytocin system, and buffering effects of either activation of the endogenous system or intranasal application of synthetic oxytocin need to be thoroughly investigated.

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Section: The Oxt System In Times Of the Covid-19 Crisismentioning

confidence: 99%

Brain oxytocin: how puzzle stones from animal studies translate into psychiatry

2020

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“…Studies diverge between no impact of intranasal oxytocin on HR 60 – 63 and decreased HR in pregnant women during oxytocin infusions 64 . Studies on HRV have reported intranasal oxytocin-induced increases at rest in healthy subjects 59 , 60 , patients with obstructive sleep apnoea 65 , in pregnant women after oxytocin infusion 64 , decreases during exposure to stress 66 , 67 or no effects at rest in both healthy individuals 63 , 66 and in men with Fragile X syndrome 68 . We have failed to detect any significant effects of a single dose of intranasal (40 IU) or intravenous infusion (10 IU) of oxytocin on HR or HRV in healthy men over an extended period of observation post dosing (14–104 min) 63 .…”

Section: Introductionmentioning

confidence: 99%

Intranasal oxytocin increases heart-rate variability in men at clinical high risk for psychosis: a proof-of-concept study

et al. 2020

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Autonomic nervous system (ANS) dysfunction (i.e., increased sympathetic and/or decreased parasympathetic activity) has been proposed to contribute to psychosis vulnerability. Yet, we still lack directed therapeutic strategies that improve ANS regulation in psychosis or at-risk states. The oxytocin system constitutes a potential therapeutic target, given its role in ANS regulation. However, whether intranasal oxytocin ameliorates autonomic regulation during emerging psychosis is currently unknown. We pooled together two datasets, one of 30 men at clinical high risk for psychosis (CHR-P), and another of 17 healthy men, who had participated in two double-blinded, placebo-controlled, randomised, crossover MRI studies with similar protocols. All participants self-administered 40 IU of intranasal oxytocin or placebo using a nasal spray. We recorded pulse plethysmography during a period of 8 min at about 1 h post dosing and estimated heart rate (HR) and high-frequency HR variability (HF-HRV), an index of cardio-parasympathetic activity. CHR-P and healthy men did not differ at resting HR or HF-HRV under placebo. We found a significant condition × treatment effect for HF-HRV, showing that intranasal oxytocin, compared with placebo, increased HF-HRV in CHR-P but not in healthy men. The main effects of treatment and condition were not significant. In this proof-of-concept study, we show that intranasal oxytocin increases cardio-parasympathetic activity in CHR-P men, highlighting its therapeutic potential to improve autonomic regulation in this clinical group. Our findings support the need for further research on the preventive and therapeutic potential of intranasal oxytocin during emerging psychosis, where we lack effective treatments.

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“…Evidence corroborating this interpretation comes from studies demonstrating that OXT reduces threat hypersensitivity in women with Borderline Personality Disorder ( 90 , 91 ) which is frequently associated with CM. Likewise, OXT enhanced the stress-buffering effects of social support in women with more severe CM exposure ( 51 ). The oxytocinergic system is highly sensitive to the adverse effects of CM, with most studies reporting decreased levels of peripheral and central OXT in a dose-dependent manner following CM exposure ( 44 – 46 ).…”

Section: Discussionmentioning

confidence: 99%

“…the Trier Social Stress Test (TSST) ( 48 ) compared to controls ( 49 ). Furthermore, human intranasal administration of OXT enhanced the stress-buffering effects of social support during the TSST ( 50 , 51 ) and we recently found that the peptide reduces amygdala reactivity to social chemosensory threat signals ( 27 ). Importantly, a plethora of studies observed that the effects of intranasal oxytocin vary as a function of social context and interindividual variables such as childhood experiences ( 52 , 53 ).…”

Section: Introductionmentioning

confidence: 98%

“…Importantly, a plethora of studies observed that the effects of intranasal oxytocin vary as a function of social context and interindividual variables such as childhood experiences ( 52 , 53 ). For instance, the stress-buffering effects of OXT after the TSST were only evident in women with higher levels of adverse childhood experiences ( 51 ), while the peptide had no significant effect on handgrip force in reaction to an infant crying in women with harsh parenting experiences ( 54 ). However, it remains to be investigated whether CM affects the effects of OXT in the context of social chemosensory threat cues.…”

Section: Introductionmentioning

confidence: 99%

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Childhood Maltreatment Alters the Neural Processing of Chemosensory Stress Signals

et al. 2020

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Accumulating evidence suggests that childhood maltreatment (CM) confers risk for psychopathology later in life by inducing hypervigilance to social threat cues such as fearful faces. However, it remains unclear whether the modulatory impact of CM extents to the olfactory domain of social communication in humans. To address this question, we examined whether CM modulates the neural processing of chemosensory threat signals in sweat and whether CM affects the stress-reducing effects of oxytocin (OXT) in this context. In a randomized, double-blind within-subject functional MRI study design, 58 healthy participants (30 females) received intranasal OXT (40 IU) or placebo (PLC) and completed a forced-choice emotion recognition task with faces of varying emotion intensities (neutral to fearful) while exposed to sweat stimuli and a non-social control odor. Axillary sweat samples were collected from 30 healthy male donors undergoing an acute psychosocial stressor (stress) and ergometer training (sport) as control in a prestudy. CM was assessed by the 25-item Childhood Trauma Questionnaire (CTQ). The final fMRI analysis included 50 healthy participants (26 females). Regression analysis showed a stress-specific association of CTQ scores with amygdala hyperreactivity, hippocampal deactivation, and increased functional connectivity between the amygdala and the hippocampus, medial orbitofrontal cortex, and the anterior cingulate cortex (ACC) under PLC. Furthermore, we observed a positive association of CTQ scores and the dampening effects of OXT on stress-related amygdala responses. Our findings suggest that CM may induce hypervigilance to chemosensory threat cues in a healthy sample due to inefficient frontolimbic inhibition of amygdala activation. Future studies should investigate whether increased recruitment of the intralimbic amygdala-hippocampus complex reflects a compensatory mechanism that prevents the development of psychopathology in those who have experienced CM. Furthermore, the results reveal that the stress-specific effects of OXT in the olfactory domain are more pronounced in participants with increasing levels of CM exposure.

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Intranasal oxytocin enhances stress-protective effects of social support in women with negative childhood experiences during a virtual Trier Social Stress Test

Cited by 40 publications

References 52 publications

Brain oxytocin: how puzzle stones from animal studies translate into psychiatry

Brain oxytocin: how puzzle stones from animal studies translate into psychiatry

Intranasal oxytocin increases heart-rate variability in men at clinical high risk for psychosis: a proof-of-concept study

Childhood Maltreatment Alters the Neural Processing of Chemosensory Stress Signals

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