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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: Assessment of the effects of psychological interventions for borderline personality disorder (BPD) found moderate to large statistically significant effects indicating a beneficial effect of DBT over TAU for anger.
Abstract: Background Psychotherapy is regarded as the first-line treatment for people with borderline personality disorder. In recent years, several disorder-specific interventions have been developed. This is an update of a review published in the Cochrane Database of Systematic Reviews in 2006. Objectives To assess the effects of psychological interventions for borderline personality disorder (BPD). Search methods We searched the following databases: CENTRAL 2010(3), MEDLINE (1950 to October 2010), EMBASE (1980 to 2010, week 39), ASSIA (1987 to November 2010), BIOSIS (1985 to October 2010), CINAHL (1982 to October 2010), Dissertation Abstracts International (31 January 2011), National Criminal Justice Reference Service Abstracts (15 October 2010), PsycINFO (1872 to October Week 1 2010), Science Citation Index (1970 to 10 October 2010), Social Science Citation Index (1970 to 10 October 2010), Sociological Abstracts (1963 to October 2010), ZETOC (15 October 2010) and the metaRegister of Controlled Trials (15 October 2010). In addition, we searched Dissertation Abstracts International in January 2011 and ICTRP in August 2011. Selection criteria Randomised studies with samples of patients with BPD comparing a specific psychotherapeutic intervention against a control intervention without any specific mode of action or against a comparative specific psychotherapeutic intervention. Outcomes included overall BPD severity, BPD symptoms (DSM-IV criteria), psychopathology associated with but not specific to BPD, attrition and adverse effects. Data collection and analysis Two review authors independently selected studies, assessed the risk of bias in the studies and extracted data. Main results Twenty-eight studies involving a total of 1804 participants with BPD were included. Interventions were classified as comprehensive psychotherapies if they included individual psychotherapy as a substantial part of the treatment programme, or as non-comprehensive if they did not. Among comprehensive psychotherapies, dialectical behaviour therapy (DBT), mentalisation-based treatment in a partial hospitalisation setting (MBT-PH), outpatient MBT (MBT-out), transference-focused therapy (TFP), cognitive behavioural therapy (CBT), dynamic deconstructive psychotherapy (DDP), interpersonal psychotherapy (IPT) and interpersonal therapy for BPD (IPT-BPD) were tested against a control condition. Direct comparisons of comprehensive psychotherapies included DBT versus client-centered therapy (CCT); schema-focused therapy (SFT) versus TFP; SFT versus SFT plus telephone availability of therapist in case of crisis (SFT+TA); cognitive therapy (CT) versus CCT, and CT versus IPT. Non-comprehensive psychotherapeutic interventions comprised DBT-group skills training only (DBT-ST), emotion regulation group therapy (ERG), schema-focused group therapy (SFT-G), systems training for emotional predictability and problem solving for borderline personality disorder (STEPPS), STEPPS plus individual therapy (STEPPS+IT), manual-assisted cognitive treatment (MACT) and psychoeducation (PE). The only direct comparison of an non-comprehensive psychotherapeutic intervention against another was MACT versus MACT plus therapeutic assessment (MACT+). Inpatient treatment was examined in one study where DBT for PTSD (DBT-PTSD) was compared with a waiting list control. No trials were identified for cognitive analytical therapy (CAT). Data were sparse for individual interventions, and allowed for meta-analytic pooling only for DBT compared with treatment as usual (TAU) for four outcomes. There were moderate to large statistically significant effects indicating a beneficial effect of DBT over TAU for anger (n = 46, two RCTs; standardised mean difference (SMD) -0.83, 95% confidence interval (CI) -1.43 to -0.22; I2 = 0%), parasuicidality (n = 110, three RCTs; SMD -0.54, 95% CI -0.92 to -0.16; I2 = 0%) and mental health (n = 74, two RCTs; SMD 0.65, 95% CI 0.07 to 1.24 I2 = 30%). There was no indication of statistical superiority of DBT over TAU in terms of keeping participants in treatment (n = 252, five RCTs; risk ratio 1.25, 95% CI 0.54 to 2.92). All remaining findings were based on single study estimates of effect. Statistically significant between-group differences for comparisons of psychotherapies against controls were observed for BPD core pathology and associated psychopathology for the following interventions: DBT, DBT-PTSD, MBT-PH, MBT-out, TFP and IPT-BPD. IPT was only indicated as being effective in the treatment of associated depression. No statistically significant effects were found for CBT and DDP interventions on either outcome, with the effect sizes moderate for DDP and small for CBT. For comparisons between different comprehensive psychotherapies, statistically significant superiority was demonstrated for DBT over CCT (core and associated pathology) and SFT over TFP (BPD severity and treatment retention). There were also encouraging results for each of the non-comprehensive psychotherapeutic interventions investigated in terms of both core and associated pathology. No data were available for adverse effects of any psychotherapy. Authors' conclusions There are indications of beneficial effects for both comprehensive psychotherapies as well as non-comprehensive psychotherapeutic interventions for BPD core pathology and associated general psychopathology. DBT has been studied most intensely, followed by MBT, TFP, SFT and STEPPS. However, none of the treatments has a very robust evidence base, and there are some concerns regarding the quality of individual studies. Overall, the findings support a substantial role for psychotherapy in the treatment of people with BPD but clearly indicate a need for replicatory studies.

548 citations

Journal ArticleDOI
TL;DR: The mechanisms of OXT expression and release, expression and binding of the OXTR in brain and periphery, OX TR-coupled signaling cascades, and their involvement in behavioral outcomes are discussed to assemble a comprehensive picture of the central and peripheral OXT system.
Abstract: The many facets of the oxytocin (OXT) system of the brain and periphery elicited nearly 25,000 publications since 1930 (see FIGURE 1, as listed in PubMed), which revealed central roles for OXT and ...

510 citations


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

  • ...OXT reversed their disorder-induced high threat sensitivity, as reflected by a higher dynamics of eye fixation and increased amygdala reactivity (measured with fMRI) in response to angry faces (77)....

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Journal ArticleDOI
TL;DR: Results strengthen the assumption that dysfunctional dorsolateral prefrontal and limbic brain regions are a hallmark feature of BPD and therefore are consistent with the conceptualization of B PD as an emotion dysregulation disorder.

244 citations

Journal ArticleDOI
TL;DR: The synergistic or antagonistic interaction of psychotherapies and drugs for treating personality disorder should be studied in conjunction with their mechanisms of change throughout the development of each.

234 citations

Journal ArticleDOI
TL;DR: It appears that oxytocin motivates and enables humans to like and empathize with others in their groups, comply with group norms and cultural practices, and extend and reciprocate trust and cooperation, which may give rise to intergroup discrimination and sometimes defensive aggression against threatening out-groups.

204 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
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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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