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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TL;DR: This study provides first evidence that oxytocin plasma levels may predict the outcome of psychotherapy in chronic depression, and these findings need to be replicated in larger randomized, controlled trials.
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TL;DR: The results suggest that BPD subjects expect higher volatility than control subjects and lay the groundwork for a neurocomputational dissection of social and nonsocial belief updating in BPD, which holds promise for the development of novel clinical interventions that more directly target pathophysiology.
19 citations
Cites background from "Oxytocin and Reduction of Social Th..."
...Previous work in noninteractive paradigms, such as Reading the Mind in the Eyes and morphed face challenges, has identified a strong negative attribution bias [reviewed in (19,20)]....
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TL;DR: This review focuses on the potential use of intranasal oxytocin (OXT), which has key roles in the regulation of complex social cognition and behaviors, to target symptoms of interpersonal dysfunction in BPD.
Abstract: Borderline personality disorder (BPD) is a common mental disorder characterized by a pervasive pattern of emotional Borderline personality disorder (BPD) is a common mental disorder characterized by a pervasive pattern of emotional lability, impulsivity, interpersonal difficulties, identity disturbances, and disturbed cognition. Traditional pharmacotherapies are effective in treating some of these core symptoms but have only modest effects on the domain of interpersonal dysfunction of BPD. Thus there is a need to develop new, neurobiologically informed pharmacological treatments for BPD. This review focuses on the potential use of intranasal oxytocin (OXT), which has key roles in the regulation of complex social cognition and behaviors, to target symptoms of interpersonal dysfunction in BPD. Surprisingly, despite promising data on the prosocial effects of OXT, only 5 trials in BPD have been published to date. These trials show mixed results with on one hand, a decrease of emotional responses to stress and on the other hand, some "paradoxical" reactions with worsened interpersonal anxiety and decreased cooperative behavior. These mixed results are interpreted according to different theoretical models and also in light of some methodological limitations. Further studies are needed to understand the effect of OXT in patients with BPD and ongoing clinical trials will provide some answers to remaining questions on the use of OXT in BPD. Recommendations for future studies are also proposed in this review.
18 citations
TL;DR: Intranasally administered oxytocin was found to strengthen avoidance behavior to social threat cues and to normalize fast action tendencies in BPD, the second report of deficient fast, automatic avoidance responses in terms of approach behavior toward interpersonal threat cues in patients with BPD.
Abstract: Background: Interpersonal deficits are a core symptom of borderline personality disorder (BPD), which could be related to increased social threat sensitivity and a tendency to approach rather than avoid interpersonal threats. The neuropeptide oxytocin has been shown to reduce threat sensitivity in patients with BPD and to modify approach-avoidance behavior in healthy volunteers. Methods: In a randomized, double-blind placebo-controlled between-subject design, 53 unmedicated women with BPD and 61 healthy women participated in an approach-avoidance task 75 min after intranasal substance administration (24 IU of oxytocin or placebo). The task assesses automatic approach-avoidance tendencies in reaction to facial expressions of happiness and anger. Results: While healthy participants responded faster to happy than angry faces, the opposite response pattern, that is, faster reactions to angry than happy faces, was found in patients with BPD. In the oxytocin condition, the "congruency effect" (i.e., faster avoidance of facial anger and approach of facial happiness vice versa) was increased in both groups. Notably, patients with BPD exhibited a congruency effect toward angry faces in the oxytocin but not in the placebo condition. Conclusions: This is the second report of deficient fast, automatic avoidance responses in terms of approach behavior toward interpersonal threat cues in patients with BPD. Intranasally administered oxytocin was found to strengthen avoidance behavior to social threat cues and, thus, to normalize fast action tendencies in BPD. Together with the previously reported oxytocinergic reduction of social threat hypersensitivity, these results suggest beneficial effects of oxytocin on interpersonal dysfunctioning in BPD.
16 citations
Cites background from "Oxytocin and Reduction of Social Th..."
...Oxytocin effects on the amygdala were also observed in patients with BPD who showed not only less fast and less frequent saccades but also lower amygdala activity toward angry eyes compared to patients in the placebo group (7)....
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...Furthermore, faster initial saccades into the eyes—themost threatening part—of angry faces in patients with BPD suggest approach rather than avoidance behavior to interpersonal threat cues (7)....
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...Second, the above-mentioned tendency for faster and more saccades toward the eyes of angry faces was not found in patients with BPD following intranasal oxytocin administration, suggesting a decrease of social threat hypersensitivity (7)....
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...For example, patients with BPD show faster initial saccades into the eyes of angry faces, (7) are more likely to recognize even subtle signals of anger in facial stimuli (5), and misconstrue happy, fearful, or neutral faces more often as angry (6)....
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References
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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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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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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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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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