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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: The evidence demonstrating abnormalities in social cognition in schizophrenia, major depressive disorder, and bipolar disorder, as well as the neurobiology of social cognition including the role of oxytocin are described.

45 citations


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

  • ...In addition, increased attention toward the eye region of facial stimuli (measured by eye gaze or reaction time) has been found after oxytocin administration (Bertsch et al., 2013; Brune et al., 2013; Domes et al., 2013; Tollenaar et al., 2013)....

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  • ...) to negative (decreased trust and cooperation) (Bartz et al., 2011a; Bertsch et al., 2013; Brune et al., 2013; Ebert et al., 2013; Simeon et al., 2011)....

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Journal ArticleDOI
TL;DR: In this paper, the effects of a single intranasal oxytocin administration (40 IU) on amygdala reactivity to happy, neutral and fearful faces in 41 recently trauma-exposed men and women showing moderate to high distress after initial post-trauma screening.
Abstract: UNLABELLED There is a need for effective, early post-trauma preventive interventions for post-traumatic stress disorder (PTSD). Attenuating amygdala hyperreactivity early post-trauma, a likely PTSD vulnerability factor, may decrease PTSD risk. Since oxytocin modulates amygdala reactivity to emotional stimuli, oxytocin administration early post-trauma may be a promising candidate for PTSD prevention. In a randomized double-blind placebo-controlled fMRI study, we investigated effects of a single intranasal oxytocin administration (40 IU) on amygdala reactivity to happy, neutral and fearful faces in 41 recently trauma-exposed men and women showing moderate to high distress after initial post-trauma screening. We explored treatment interactions with sex. Participants were scanned within 11 days post-trauma. Compared with placebo, oxytocin significantly increased right amygdala reactivity to fearful faces. There was a significant treatment by sex interaction on amygdala reactivity to neutral faces, with women showing increased left amygdala reactivity after oxytocin. These findings indicate that a single oxytocin administration may enhance fearful faces processing in recently trauma-exposed individuals and neutral faces processing in recently trauma-exposed women. These observations may be explained by oxytocin-induced increased salience processing. Clinical implications of these findings for PTSD prevention should be further investigated. TRIAL REGISTER Netherlands Trial Registry; Boosting Oxytocin after trauma: Neurobiology and the Development of Stress-related psychopathology (BONDS); NTR3190; http://www.trialregister.nl/trialreg/admin/rctview.asp?TC = 3190.

43 citations


Cites background or methods or result from "Oxytocin and Reduction of Social Th..."

  • ...Of note, in healthy women, OT administration has previously been demonstrated to enhance left (Domes et al., 2010) and right (Bertsch et al., 2013) amygdala reactivity to fearful (Domes et al., 2010) and angry (Bertsch et al., 2013) facial expressions....

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  • ..., 2010) and angry (Bertsch et al., 2013) facial expressions....

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  • ...However, the results are in contrast with findings in healthy men (Kirsch et al., 2005; Domes et al., 2007; Gamer et al., 2010), male GSAD patients (Labuschagne et al., 2010), and women with BPD (Bertsch et al., 2013) and contrary to our expectations for recently trauma-exposed individuals....

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  • ...right amygdala reactivity to angry (Bertsch et al., 2013), and left...

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  • ...Of note, in BPD patients, in contrast to findings of beneficial OT effects on stress and fear processing (Simeon et al., 2011; Bertsch et al., 2013), adverse effects from OT administration on social behavior were also observed (Bartz et al....

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01 Jan 2016
TL;DR: In this article, the authors investigated the behavioural and electrophysiological correlates underlying facial emotion processing in individuals with BPD and found that BPD patients were more likely than controls to classify predominantly happy faces as angry.
Abstract: BACKGROUND Borderline personality disorder (BPD) is characterized by a negative perception of others. Previous studies have revealed deficits and biases in facial emotion recognition. This study investigates the behavioural and electrophysiological correlates underlying facial emotion processing in individuals with BPD. METHODS The present study was conducted between July 2012 and May 2014. In an emotion classification task, unmedicated female patients with BPD as well as healthy women had to classify faces displaying blends of anger and happiness while the electroencephalogram was recorded. We analyzed visual event-related potentials (ERPs) reflecting early (P100), structural (N170) and categorical (P300) facial processing in addition to behavioural responses. RESULTS We included 36 women with BPD and 29 controls in our analysis. Patients with BPD were more likely than controls to classify predominantly happy faces as angry. Independent of facial emotion, women with BPD showed enhanced early occipital P100 amplitudes. Additionally, temporo-occipital N170 amplitudes were reduced at right hemispherical electrode sites. Centroparietal P300 amplitudes were reduced particularly for predominantly happy faces and increased for highly angry faces in women with BPD, whereas in healthy volunteers this component was modulated by both angry and happy facial affect. LIMITATIONS Our sample included only women, and no clinical control group was investigated. CONCLUSION Our findings suggest reduced thresholds for facial anger and deficits in the discrimination of facial happiness in individuals with BPD. This biased perception is associated with alterations in very early visual as well as deficient structural and categorical processing of faces. The current data could help to explain the negative perception of others that may be related to the patients' impairments in interpersonal functioning.

43 citations

Journal ArticleDOI
TL;DR: BPD patients did not experience general deficits in facial emotion processing, but a specific hypersensitivity for and deficits in detailed evaluation of threat cues, which was particularly enhanced in aggressive patients, might benefit from relocating attention towards positive information andDetailed evaluation of social cues.
Abstract: Threat sensitivity is a prominent predictor of interpersonal dysfunctions in borderline personality disorder (BPD), leading to intense, aversive feelings of threat and eventually dysfunctional behaviors, such as aggression. In the present study, BPD patients and healthy volunteers classified angry, fearful, neutral, and happy faces presented for 150 ms or 5,000 ms to investigate initial saccades and facial scanning. Patients more often wrongly identified anger, responded slower to all faces, and made faster saccades towards the eyes of briefly presented neutral faces and slower saccades away from fearful eyes compared with healthy volunteers. Latency of initial saccades and fixation duration correlated negatively with the patients’ aggressiveness. Supporting previous results, BPD patients did not experience general deficits in facial emotion processing, but a specific hypersensitivity for and deficits in detailed evaluation of threat cues, which was particularly enhanced in aggressive patients. Interventi...

42 citations


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

  • ...Although the exact reasons for these divergent results remain unclear, some important differences in the experimental settings need to be considered: The previously reported results (Bertsch et al., 2013) were found in a pharmacological stimulation study in which participants classified briefly presented (150 ms) angry, fearful, and happy faces in the MRI scanner after a nasal administration of oxytocin or a placebo....

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  • ...With regard to the eye-tracking data, we expected an enhanced proportion as well as a shorter latency of initial saccades towards the eyes of threatening (angry and fearful) faces in patients with BPD compared with healthy volunteers in both presentation time conditions, replicating our former findings (Bertsch et al., 2013)....

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  • ...Similar to our former study (Bertsch et al., 2013), patients with BPD and healthy volunteers took part in an emotion classification task with angry, fearful, happy—and this time also neutral—faces initially fixated at the mouth or eye region....

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  • ...So far, reflexive saccades during facial emotion processing in patients with BPD have only been assessed in one study (Bertsch et al., 2013)....

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  • ...In some regards, the results of the present study differ from those of our previous eye-tracking study (Bertsch et al., 2013), in which we found more and faster initial saccades towards the eyes of angry and fearful faces as well as faster responses to angry faces in the total sample of patients with BPD compared with healthy volunteers....

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Journal ArticleDOI
TL;DR: The results indicate reduced lateral prefrontal-amygdala communication during emotional action control in anger-prone women with BPD, which provides a possible neural mechanism underlying difficulties with controlling emotional impulses in patients with B PD.
Abstract: BACKGROUND Difficulty in controlling emotional impulses is a crucial component of borderline personality disorder (BPD) that often leads to destructive, impulsive behaviours against others. In line with recent findings in aggressive individuals, deficits in prefrontal amygdala coupling during emotional action control may account for these symptoms. METHODS To study the neurobiological correlates of altered emotional action control in individuals with BPD, we asked medication-free, anger-prone, female patients with BPD and age- and intelligence-matched healthy women to take part in an approach-avoidance task while lying in an MRI scanner. The task required controlling fast behavioural tendencies to approach happy and avoid angry faces. Additionally, before the task we collected saliva testosterone and self-reported information on tendencies to act out anger and correlated this with behavioural and functional MRI (fMRI) data. RESULTS We included 30 patients and 28 controls in our analysis. Patients with BPD reported increased tendencies to act out anger and were faster in approaching than avoiding angry faces than with healthy women, suggesting deficits in emotional action control in women with BPD. On a neural level, controlling fast emotional action tendencies was associated with enhanced activation in the antero- and dorsolateral prefrontal cortex across groups. Healthy women showed a negative coupling between the left dorsolateral prefrontal cortex and right amygdala, whereas this was absent in patients with BPD. LIMITATIONS Specificity of results to BPD and sex differences remain unknown owing to the lack of clinical control groups and male participants. CONCLUSION The results indicate reduced lateral prefrontal-amygdala communication during emotional action control in anger-prone women with BPD. The findings provide a possible neural mechanism underlying difficulties with controlling emotional impulses in patients with BPD.

40 citations

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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