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Journal ArticleDOI

Oxytocin and Reduction of Social Threat Hypersensitivity in Women With Borderline Personality Disorder

TL;DR: Borderline patients exhibit a hypersensitivity to social threat in early, reflexive stages of information processing, and oxytocin may decrease social threat hypersensitivity and thus reduce anger and aggressive behavior in borderline personality disorder or other psychiatric disorders with enhanced threat-driven reactive aggression.
Abstract: Objective: Patients with borderline personality disorder are characterized by emotional hyperarousal with increased stress levels, anger proneness, and hostile, impulsive behaviors. They tend to ascribe anger to ambiguous facial expressions and exhibit enhanced and prolonged reactions in response to threatening social cues, associated with enhanced and prolonged amygdala responses. Because the intranasal administration of the neuropeptide oxytocin has been shown to improve facial recognition and to shift attention away from negative social information, the authors investigated whether borderline patients would benefit from oxytocin administration. Method: In a randomized placebocontrolled double-blind group design, 40 nonmedicated, adult female patients with a current DSM-IV diagnosis of borderline personality disorder (two patients were excluded based on hormonal analyses) and 41 healthy women, matched on age, education, and IQ, took part in an emotion classification task 45 minutes after intranasal administration of 26 IU of oxytocin or placebo. Dependent variables were latencies and number or initial reflexive eye movements measured by eye tracking, manual response latencies, and blood-oxygen-level-dependent responses of theamygdalato angryandfearfulcompared with happy facial expressions. Results: Borderline patients exhibited more and faster initial fixation changes to the eyes of angry faces combined with increased amygdala activation in response to angry faces compared with the control group. These abnormal behavioral and neural patterns were normalized after oxytocin administration. Conclusions: Borderline patients exhibit a hypersensitivity to social threat in early, reflexive stages of information processing. Oxytocin may decrease social threat hypersensitivity and thus reduce anger and aggressive behavior in borderline personality disorder or other psychiatric disorders with enhanced threat-driven reactive aggression. (Am J Psychiatry 2013; 170:1169–1177)

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Journal ArticleDOI
TL;DR: Convergent neural substrates and the underlying neuropsychological mechanisms for IN-OT effects on social and affective processes are found and the modulation of OT effects by valence have critical implications.
Abstract: The hypothalamic peptide oxytocin (OT) is crucial in social adaptation and used to treat emotional and social deficits. Here, we conducted a systematic, quantitative meta-analysis of functional-MRI studies intranasally administering OT (IN-OT) to uncover neural substrates underlying the IN-OT effects and to elucidate differential IN-OT effects between healthy and clinical populations. Meta-analyses were conducted on 66 IN-OT fMRI studies, stratified by psychopathology, valence and sex. IN-OT increased bilateral amygdala, caudate head, and superior temporal activity in healthy individuals and increased dorsal anterior cingulate activity in patients. Moreover, IN-OT decreased amygdala activity in both patients and healthy individuals but did so to a greater degree in patients than healthy individuals. The OT-increased amygdala activity was only found on the negative social and affective processes, whereas the OT-decreased amygdala activity was mainly contributed by contrasts on negative-valenced processes. IN-OT increased parahippocampal activity and decreased amygdala activity during negative socio-affective processing. During positive socio-affective processes, IN-OT increased caudate head activity. This study indicates convergent neural substrates and the underlying neuropsychological mechanisms for IN-OT effects on social and affective processes. The common and different effects of IN-OT on patients and healthy individuals and the modulation of OT effects by valence have critical implications.

75 citations


Cites background from "Oxytocin and Reduction of Social Th..."

  • ...…and affective processes (Gamer et al., 2010; Rilling et al., 2012,2014; Rupp et al., 2013), whereas the OT-decreased amygdala activity was mainly contributed by contrasts on negative-valenced processes (Petrovic et al., 2008; Labuschagne et al., 2010; Bertsch et al., 2013; Rupp et al., 2014)....

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Journal ArticleDOI
TL;DR: Support is provided for a direct nose-to-brain effect, independent of blood absorption, of low-dose OT delivered from a Breath Powered device.
Abstract: Despite the promise of intranasal oxytocin (OT) for modulating social behavior, recent work has provided mixed results. This may relate to suboptimal drug deposition achieved with conventional nasal sprays, inter-individual differences in nasal physiology and a poor understanding of how intranasal OT is delivered to the brain in humans. Delivering OT using a novel 'Breath Powered' nasal device previously shown to enhance deposition in intranasal sites targeted for nose-to-brain transport, we evaluated dose-dependent effects on social cognition, compared response with intravenous (IV) administration of OT, and assessed nasal cavity dimensions using acoustic rhinometry. We adopted a randomized, double-blind, double-dummy, crossover design, with 16 healthy male adults completing four single-dose treatments (intranasal 8 IU (international units) or 24 IU OT, 1 IU OT IV and placebo). The primary outcome was social cognition measured by emotional ratings of facial images. Secondary outcomes included the pharmacokinetics of OT, vasopressin and cortisol in blood and the association between nasal cavity dimensions and emotional ratings. Despite the fact that all the treatments produced similar plasma OT increases compared with placebo, there was a main effect of treatment on anger ratings of emotionally ambiguous faces. Pairwise comparisons revealed decreased ratings after 8 IU OT in comparison to both placebo and 24 IU OT. In addition, there was an inverse relationship between nasal valve dimensions and anger ratings of ambiguous faces after 8-IU OT treatment. These findings provide support for a direct nose-to-brain effect, independent of blood absorption, of low-dose OT delivered from a Breath Powered device.

72 citations

Journal ArticleDOI
TL;DR: The reduction in OT levels in CD patients after social exclusion may contribute to their interpersonal dysfunction and their difficulty in coping adequately with aversive social cues.

69 citations

Journal ArticleDOI
TL;DR: Given the similar consequences of elevated central GABA and OXT activity on maternal anxiety and depression, balanced and partly reciprocal interactions between these two systems may be essential for their effects on maternal emotional and mood states, in addition to other aspects of postpartum behaviour and physiology.
Abstract: Peripartum hormones and sensory cues from young modify the maternal brain in ways that can render females either at risk for, or resilient to, elevated anxiety and depression. The neurochemical systems underlying these aspects of maternal emotional and mood states include the inhibitory neurotransmitter GABA and the neuropeptide oxytocin (OXT). Data from laboratory rodents indicate that increased activity at the GABA(A) receptor contributes to the postpartum suppression of anxiety-related behaviour that is mediated by physical contact with offspring, whereas dysregulation in GABAergic signalling results in deficits in maternal care, as well as anxiety- and depression-like behaviours during the postpartum period. Similarly, activation of the brain OXT system accompanied by increased OXT release within numerous brain sites in response to reproductive stimuli also reduces postpartum anxiety- and depression-like behaviours. Studies of peripartum women are consistent with these findings in rodents. Given the similar consequences of elevated central GABA and OXT activity on maternal anxiety and depression, balanced and partly reciprocal interactions between these two systems may be essential for their effects on maternal emotional and mood states, in addition to other aspects of postpartum behaviour and physiology.

69 citations

Journal ArticleDOI
TL;DR: The results suggest that OT may decrease the stress of negative social interactions among men, whereas these effects were not found in women interacting with human partners, and support continued investigation into the possible efficacy of OT as a treatment for anxiety disorders.
Abstract: Anxiety disorders are characterized by hyperactivity in both the amygdala and the anterior insula. Interventions that normalize activity in these areas may therefore be effective in treating anxiety disorders. Recently, there has been significant interest in the potential use of oxytocin (OT), as well as vasopressin (AVP) antagonists, as treatments for anxiety disorders. In this double-blind, placebo-controlled, pharmaco- fMRI study, 153 men and 151 women were randomized to treatment with either 24 IU intranasal OT, 20 IU intranasal AVP, or placebo and imaged with fMRI as they played the iterated Prisoner’s Dilemma game with same-sex human and computer partners. In men, OT attenuated the fMRI response to unreciprocated cooperation (CD), a negative social interaction, within the amygdala and anterior insula. This effect was specific to interactions with human partners. In contrast, among women, OT unexpectedly attenuated the amygdala and anterior insula response to unreciprocated cooperation from computer but not human partners. Among women, AVP did not significantly modulate the response to unreciprocated cooperation in either the amygdala or the anterior insula. However, among men, AVP attenuated the BOLD response to CD outcomes with human partners across a relatively large cluster including the amygdala and the anterior insula, which was contrary to expectations. Our results suggest that OT may decrease the stress of negative social interactions among men, whereas these effects were not found in women interacting with human partners. These findings support continued investigation into the possible efficacy of OT as a treatment for anxiety disorders.

67 citations


Cites background from "Oxytocin and Reduction of Social Th..."

  • ...…amygdala response to viewing emotional faces in healthy men (Domes et al. 2007; Kirsch et al. 2005), and also attenuates amygdala hyperactivity to fearful and angry faces in social anxiety disorder (Labuschagne et al. 2010) and borderline personality disorder (Bertsch et al. 2013), respectively....

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  • ...2010) and borderline personality disorder (Bertsch et al. 2013), respectively....

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References
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Journal ArticleDOI
TL;DR: An anatomical parcellation of the spatially normalized single-subject high-resolution T1 volume provided by the Montreal Neurological Institute was performed and it is believed that this tool is an improvement for the macroscopical labeling of activated area compared to labeling assessed using the Talairach atlas brain.

13,678 citations


"Oxytocin and Reduction of Social Th..." refers methods in this paper

  • ...Since we hypothesized modulatory effects of oxytocin in the amygdala, we applied a small-volume correction for multiple comparisons in predefined bilateral anatomical amygdala regions of interest (35)....

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Journal ArticleDOI
TL;DR: Oxytocin seems to enhance the buffering effect of social support on stress responsiveness, concur with data from animal research suggesting an important role of oxytocin as an underlying biological mechanism for stress-protective effects of positive social interactions.

1,760 citations


"Oxytocin and Reduction of Social Th..." refers background in this paper

  • ...In healthy individuals, the intranasal administration of oxytocin reduces anxiety and stress in social situations (15), enhances the recognition of facial expressions (16–19), and shifts attention from negative to positive information (20–22), although individual differences and situational factors seem to play an important role (23)....

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Book
01 Jan 1997
TL;DR: This greatly enlarged new edition of Atlas of the Human Brain provides the most detailed and accurate delineations of brain structure available and includes features which assist in the new fields of neuroscience - functional imaging, resting state imaging and tractography.
Abstract: Material and methods topographic and topometric atlas myeloarchitectonic atlas hierarchical tree.

1,515 citations


"Oxytocin and Reduction of Social Th..." refers methods in this paper

  • ...Anatomical labels for subregions within the amygdala were specified by comparing the location of activation clusters with high-resolution diagrams of the human amygdala as depicted in an anatomical atlas (36)....

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Journal ArticleDOI
TL;DR: It is shown that human amygdala function is strongly modulated by oxytocin, and this results indicate a neural mechanism for the effects of Oxytocin in social cognition in the human brain and provide a methodology and rationale for exploring therapeutic strategies in disorders in which abnormal amygdala function has been implicated, such as social phobia or autism.
Abstract: In non-human mammals, the neuropeptide oxytocin is a key mediator of complex emotional and social behaviors, including attachment, social recognition, and aggression. Oxytocin reduces anxiety and impacts on fear conditioning and extinction. Recently, oxytocin administration in humans was shown to increase trust, suggesting involvement of the amygdala, a central component of the neurocircuitry of fear and social cognition that has been linked to trust and highly expresses oxytocin receptors in many mammals. However, no human data on the effects of this peptide on brain function were available. Here, we show that human amygdala function is strongly modulated by oxytocin. We used functional magnetic resonance imaging to image amygdala activation by fear-inducing visual stimuli in 15 healthy males after double-blind crossover intranasal application of placebo or oxytocin. Compared with placebo, oxytocin potently reduced activation of the amygdala and reduced coupling of the amygdala to brainstem regions implicated in autonomic and behavioral manifestations of fear. Our results indicate a neural mechanism for the effects of oxytocin in social cognition in the human brain and provide a methodology and rationale for exploring therapeutic strategies in disorders in which abnormal amygdala function has been implicated, such as social phobia or autism.

1,477 citations


"Oxytocin and Reduction of Social Th..." refers background in this paper

  • ...anterior) amygdala to negative emotional stimuli (13, 25, 26), whichmay reflect a neural mechanism of its anxiolytic properties (24, 26)....

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Journal ArticleDOI
TL;DR: OXT and AVP are emerging as targets for novel treatment approaches — particularly in synergistic combination with psychotherapy — for mental disorders characterized by social dysfunction, such as autism, social anxiety disorder, borderline personality disorder and schizophrenia.
Abstract: The neuropeptides oxytocin (OXT) and arginine vasopressin (AVP) are evolutionarily highly conserved mediators in the regulation of complex social cognition and behaviour. Recent studies have investigated the effects of OXT and AVP on human social interaction, the genetic mechanisms of inter-individual variation in social neuropeptide signalling and the actions of OXT and AVP in the human brain as revealed by neuroimaging. These data have advanced our understanding of the mechanisms by which these neuropeptides contribute to human social behaviour. OXT and AVP are emerging as targets for novel treatment approaches — particularly in synergistic combination with psychotherapy — for mental disorders characterized by social dysfunction, such as autism, social anxiety disorder, borderline personality disorder and schizophrenia.

1,436 citations


"Oxytocin and Reduction of Social Th..." refers background in this paper

  • ...It has therefore been suggested that borderline patients who are hypersensitive to negative, threatening social information may benefit from intranasal oxytocin administration (29)....

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