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: 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
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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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
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
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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TL;DR: Eye-tracking data revealed a pronounced influence of active avoidance of direct eye contact on atypical gaze in ASDs, and the combination of avoidance and reduced orientation into an individual index predicted emotional recognition performance.
Abstract: Atypical scan paths on emotional faces and reduced eye contact represent a prominent feature of autism symptomatology, yet the reason for these abnormalities remains a puzzle Do individuals with autism spectrum disorders (ASDs) fail to orient toward the eyes or do they actively avoid direct eye contact? Here, we used a new task to investigate reflexive eye movements on fearful, happy, and neutral faces Participants (ASDs: 12; controls: 11) initially fixated either on the eyes or on the mouth By analyzing the frequency of participants' eye movements away from the eyes and toward the eyes, respectively, we explored both avoidance and orientation reactions The ASD group showed a reduced preference for the eyes relative to the control group, primarily characterized by more frequent eye movements away from the eyes Eye-tracking data revealed a pronounced influence of active avoidance of direct eye contact on atypical gaze in ASDs The combination of avoidance and reduced orientation into an individual index predicted emotional recognition performance Crucially, this result provides evidence for a direct link between individual gaze patterns and associated social symptomatology These findings thereby give important insights into the social pathology of ASD, with implications for future research and interventions
163 citations
"Oxytocin and Reduction of Social Th..." refers background in this paper
...Initial eye movements provide a biologically relevant measure for the first reflexive orientation of visual attention to salient features of emotional stimuli (10) and are sensitive to differences in social competences (11, 12)....
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...In addition, when initially fixating on the eyes of threatening faces, borderline patients in the placebo condition also exhibited earlier fixation changes away from the eye region, again combined with increased amygdala activity, supporting the hypothesis that excessive emotional arousal mediates the avoidance of the eyes (11)....
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TL;DR: The findings indicate an aggressivistic evaluation bias and elevated levels of interpersonal problems in individuals with BPD as suggested in the cognitive theory.
158 citations
"Oxytocin and Reduction of Social Th..." refers background in this paper
...Regarding the perception of social threat, they tend to attribute resentment and aggression to others (5) and are more likely to ascribe anger to ambiguous facial expressions (6), favoring conflicts and reactive aggression....
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TL;DR: Different patterns of amygdala activity in combination with differing patterns of gaze behavior between groups triggered by direct eye contact and mouth fixation, suggest a dysfunctional profile of the amygdala in ASD involving an interplay of both eye-avoidance processing and reduced orientation.
Abstract: Reduced focus toward the eyes is a characteristic of atypical gaze on emotional faces in autism spectrum disorders (ASD). Along with the atypical gaze, aberrant amygdala activity during face processing compared with neurotypically developed (NT) participants has been repeatedly reported in ASD. It remains unclear whether the previously reported dysfunctional amygdalar response patterns in ASD support an active avoidance of direct eye contact or rather a lack of social attention. Using a recently introduced emotion classification task, we investigated eye movements and changes in blood oxygen level-dependent (BOLD) signal in the amygdala with a 3T MRI scanner in 16 autistic and 17 control adult human participants. By modulating the initial fixation position on faces, we investigated changes triggered by the eyes compared with the mouth. Between-group interaction effects revealed different patterns of gaze and amygdalar BOLD changes in ASD and NT: Individuals with ASD gazed more often away from than toward the eyes, compared with the NT group, which showed the reversed tendency. An interaction contrast of group and initial fixation position further yielded a significant cluster of amygdala activity. Extracted parameter estimates showed greater response to eyes fixation in ASD, whereas the NT group showed an increase for mouth fixation. The differing patterns of amygdala activity in combination with differing patterns of gaze behavior between groups triggered by direct eye contact and mouth fixation, suggest a dysfunctional profile of the amygdala in ASD involving an interplay of both eye-avoidance processing and reduced orientation.
146 citations
"Oxytocin and Reduction of Social Th..." refers background in this paper
...Initial eye movements provide a biologically relevant measure for the first reflexive orientation of visual attention to salient features of emotional stimuli (10) and are sensitive to differences in social competences (11, 12)....
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TL;DR: It is suggested that oxytocin may have a beneficial impact on emotional regulation in BPD, which merits further investigation and could have important treatment implications.
143 citations
"Oxytocin and Reduction of Social Th..." refers background in this paper
...In emotionally hyperaroused borderline patients, who exhibit exaggerated allocation of attention toward the most threatening features of social information, a downregulation of social salience by oxytocin may help to reduce stress reactivity (30), hostility, and reactive aggressive behaviors....
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...Consistent with this assumption, oxytocin was shown to reduce social stress (30) in borderline patients, although it did not increase trust and cooperation during a game paradigm (31)....
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TL;DR: The findings indicate dysregulations in the oxytocin system of patients diagnosed with BPD with more longitudinal research being necessary to disentangle the relationship between childhood adversities, oxytoc in system, and psychopathology.
142 citations
"Oxytocin and Reduction of Social Th..." refers background in this paper
...Thus, future studies should address differential oxytocinergic modulation of social cognition in subtypes of borderline patients and disentangle an apparently complex relationship of childhood adversity, attachment, and oxytocin in borderline personality disorder (41)....
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