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: It is proposed that this literature can be informed by an interactionist approach in which the effects of oxytocin are constrained by features of situations and/or individuals.
1,311 citations
"Oxytocin and Reduction of Social Th..." refers background or result in this paper
...This contrasts sharply with the previous study of healthy men (13), calling for a direct comparison of male and female participants in future studies, while strengthening the hypothesized gender- and trait-dependent oxytocinergic modulation of social behavior (23)....
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...Taken together, oxytocin may be a powerful modulator of the salience of social information (23) optimizing reflexive processing of social cues, as reflected in amygdala activation and initial eye movements....
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...Our results, therefore, do not support a general oxytocinergic enhancement (13) but rather indicate a trait-dependent modulation of social salience, which may help to optimize an individual’s social behavior (23)....
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...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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TL;DR: Three peptides were administered intranasally and found that they achieved direct access to the cerebrospinal fluid (CSF) within 30 minutes, bypassing the bloodstream.
Abstract: Neuropeptides act as neuronal messengers in the brain, influencing many neurobehavioral functions1. Their experimental and therapeutic use in humans has been hampered because, when administered systemically, these compounds do not readily pass the blood–brain barrier, and they evoke potent hormone-like side effects when circulating in the blood2,3. We administered three peptides, melanocortin(4–10) (MSH/ACTH(4–10)), vasopressin and insulin, intranasally and found that they achieved direct access to the cerebrospinal fluid (CSF) within 30 minutes, bypassing the bloodstream.
1,259 citations
"Oxytocin and Reduction of Social Th..." refers background in this paper
...Because central nervous oxytocin levels reach a plateau approximately 40 minutes after substance administration (34), participants received oxytocin or placebo 45 minutes before fMRI scanning (scan duration, ,45 minutes)....
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TL;DR: Oxytocin improves the ability to infer the mental state of others from social cues of the eye region, and might play a role in the pathogenesis of autism spectrum disorder, which is characterized by severe social impairment.
1,209 citations
TL;DR: It is possible to assess personality disorders with reasonably good reliability in different nations, languages, and cultures using a semistructured clinical interview that experienced clinicians find relevant, meaningful, and user-friendly.
Abstract: Background: One of the aims of the World Health Organization/Alcohol, Drug Abuse, and Mental Health Administration joint program on psychiatric diagnosis and classification is the development and standardization of diagnostic assessment instruments for use in clinical research worldwide. The International Personality Disorder Examination (IPDE) is a semistructured clinical interview compatible with the International Classification of Diseases, Tenth Revision , and the DMS-III-R classification systems. This is the first report of the results of a field trial to investigate the feasibility of using the IPDE to assess personality disorders worldwide. Methods: The IPDE was administered by 58 psychiatrists and clinical psychologists to 716 patients enrolled in clinical facilities at 14 participating centers in 11 countries in North America, Europe, Africa, and Asia. To determine interrater reliability, 141 of the IPDEs (20%) were independently rated by a silent observer. To determine temporal stability, 243 patients (34%) were reexamined after an average interval of 6 months. Results: The IPDE proved acceptable to clinicians and demonstrated an interrater reliability and temporal stability roughly similar to instruments used to diagnose the psychoses, mood, anxiety, and substance use disorders. Conclusion: It is possible to assess personality disorders with reasonably good reliability in different nations, languages, and cultures using a semistructured clinical interview that experienced clinicians find relevant, meaningful, and user-friendly.
936 citations
TL;DR: In vivo, local blue-light-induced endogenous OT release robustly decreased freezing responses in fear-conditioned rats and demonstrates that OT release from local axonal endings can specifically control region-associated behaviors.
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"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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...Neuroimaging and animal studies indicate that oxytocinergicmodulation of social behavior is related to its effects on the amygdala (24)....
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