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: Neural substrates of trustworthiness appraisal are associated with the lateral prefrontal cortex and insula, not amygdala, suggesting that untrustworthy stimuli do not elicit a subcortical threat response.
13 citations
TL;DR: Among women, physical IPV modulated skin conductance in those administered OT, and OT interacted with physical and psychological IPV to yield less positive subjective and behavioral responses, which support emerging literature on sex differences in response to OT.
Abstract: Emerging literature indicates individual and contextual differences impact response to oxytocin (OT). Intimate partner violence (IPV) is one chronic stressor that may moderate OT response. To test the hypothesis that IPV moderates the association between OT and reactivity to a dyadic conflict task, data from a larger randomized controlled study was collected from heterosexual couples (N = 60 individuals; 30 couples) at high risk for IPV due to substance misuse. Partners within each dyad completed a 10-minute dyadic conflict task in the laboratory, and then self-administered a single dose of OT (40 IU) or placebo. Forty-five minutes later, participants completed another 10-minute dyadic conflict task. Stress reactivity was measured before and after the second conflict task using neuroendocrine (i.e., salivary cortisol), physiological (i.e., skin conductance), and subjective responses. Couple conflict behaviors were observed during the conflict tasks and assessed using a validated coding system. Among women, physical IPV modulated skin conductance in those administered OT, and OT interacted with physical and psychological IPV to yield less positive subjective and behavioral responses. No main or moderating effects were found for men. Findings support emerging literature on sex differences in response to OT. Future research is needed to effectively translate OT into therapeutic intervention.
12 citations
TL;DR: A narrative review of medication management in borderline personality disorder (BPD), using a single vignette to explore the limitations of prescribing multiple medications and the factors contributing to polypharmacy, and describes how medication regimens can be reduced to a necessary minimum.
Abstract: LEARNING OBJECTIVES After participating in this activity, learners should be better able to:• Assess medication management in patients with borderline personality disorder (BPD)• Evaluate the role of deprescribing as an active intervention in patients with BPD treated with polypharmacy ABSTRACT: Psychopharmacology in borderline personality disorder (BPD) is complicated by comorbid disorders, substance use, sensitivity to side effects, risk of self-harm through medication misuse, and intense but transient symptoms. Patients' relationships with medications may range from tenuous to highly enmeshed, and may profoundly influence the response to treatment. For these reasons, awareness of current evidence and flexible approaches are particularly relevant to prescribing in BPD. In this narrative review, we illustrate the current status of medication management in BPD by focusing on polypharmacy. We use a single vignette to explore the limitations of prescribing multiple medications and the factors contributing to polypharmacy. With the same vignette, and using the framework of deprescribing, we describe how medication regimens can be reduced to a necessary minimum. Deprescribing, originally developed in geriatric medicine, is an active intervention that involves a risk-benefit analysis for each medication, keeping in mind the patient's medical and psychiatric status and his or her preferences and values. Deprescribing lends itself well to use in psychiatry and especially in BPD because of its emphasis on the patient's preferences and on repeated conversations to revisit and update decisions. In addition to elaborating on the deprescribing framework, we provide recommendations for conducting these critical discussions about medications in BPD, with particular attention to the patient's relationship to the medication. Finally, we summarize our recommendations and strategies for implementing flexible and responsive medication management for patients with BPD. We suggest areas of future research, including testing the efficacy of targeted intermittent medication treatments.
12 citations
01 Jan 2016
TL;DR: It is found that there is limited research investigating the effects of OT on behavior and brain responses in males and females in the same design, highlighting the need for comparative research, particularly if OT is to be used as a therapeutic agent in both sexes.
Abstract: The oxytocin (OT) system in the brain is an important modulator of social behavior in mammals, including humans. Here, we provide a comprehensive review in which we discuss the evidence showing sex differences, or lack thereof, in structure and function of the brain OT system parameters in rodents and humans. We find that (1) the reported sex differences in the brain OT system are not ubiquitous, but appear to be highly species-specific and (2) actions of the OT system on behavior and neuronal responses are often sex-specific, but do not necessarily correspond with sex differences in OT system parameters. Based on these findings, we propose that sex differences in the brain OT system depend on species-specific social organizations (i.e., mating, parental, and sociality systems) and discuss sex-specific actions of OT on behavior and neuronal responses in the context of differences in social organizations. Furthermore, OT may show promise in the treatment of social dysfunction in neuropsychiatric disorders, many of which show sex differences in prevalence and treatment responses. We therefore discuss recent advances and precautions of OT as a therapeutic agent in the treatment of social dysfunction in both men and women. Overall, we find that there is limited research investigating the effects of OT on behavior and brain responses in males and females in the same design, highlighting the need for comparative research, particularly if OT is to be used as a therapeutic agent in both sexes. Given the many studies indicating a role of the brain OT system in sex-specific regulation of social behavior, an important next step will be to investigate how these effects are mediated and how they relate to the presence or absence of sex differences in brain OT system parameters.
11 citations
04 Jan 2021
TL;DR: In this article, the authors investigated interpersonal threat hypersensitivity and its association with adverse childhood experiences (ACE) in patients with BPD employing eye-tracking technology and found that patients as compared to healthy volunteers reflexively directed their gaze more quickly towards the eyes of emotional and neutral faces and did not adapt their fixation patterns according to the facial expression presented.
Abstract: Previous eye-tracking studies provide preliminary evidence for a hypersensitivity to negative, potentially threatening interpersonal cues in borderline personality disorder (BPD). From an etiological point of view, such interpersonal threat hypersensitivity might be explained by a biological vulnerability along with a history of early life adversities. The objective of the current study was to investigate interpersonal threat hypersensitivity and its association with adverse childhood experiences (ACE) in patients with BPD employing eye-tracking technology. We examined a sample of 46 unmedicated, adult female patients with BPD and 25 healthy female volunteers, matched on age and intelligence, with a well-established emotion classification paradigm with angry, fearful, happy, and neutral facial expressions. ACE were assessed retrospectively with the Childhood Trauma Questionnaire. Patients as compared to healthy volunteers reflexively directed their gaze more quickly towards the eyes of emotional and neutral faces and did not adapt their fixation patterns according to the facial expression presented. Misclassifying emotional and neutral faces as angry correlated positively with the patients’ self-reported ACE. Building on and extending earlier findings, our results are likely to suggest a visual hypervigilance towards the eyes of emotional and neutral facial expressions and a childhood trauma-related anger bias in patients with BPD. Given the lack of a clinical control group, the question whether these findings are specific for BPD has to remain open. Thus, further research is needed to elucidate the specificity of altered visual attention allocation and the role of ACE in anger recognition in patients with BPD.
11 citations
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"Oxytocin and Reduction of Social Th..." refers methods in this paper
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"Oxytocin and Reduction of Social Th..." refers methods in this paper
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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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