No drugs are currently approved for the treatment of borderline personality disorder (BPD). These studies (a randomised study and its open-label extension) aimed to evaluate the efficacy, safety and tolerability of brexpiprazole for the treatment of BPD.

The Phase 2, multicentre, randomised, double-blind, placebo-controlled, parallel-group study enrolled adult outpatients with BPD. After a 1-week placebo run-in, patients were randomised 1:1 to brexpiprazole 2–3 mg/day (flexible dose) or placebo for 11 weeks. The primary endpoint was change in Zanarini Rating Scale for BPD total score from randomisation (Week 1) to Week 10 (timing of randomisation and endpoint blinded to investigators and patients). The Phase 2/3, multicentre, open-label extension study enrolled patients who completed the randomised study; all patients received brexpiprazole 2–3 mg/day (flexible dose) for 12 weeks. Safety assessments included treatment-emergent adverse events (TEAEs).

Brexpiprazole was not statistically significantly different from placebo on the primary endpoint of the randomised study (N = 324 randomised; N = 110 analysed per treatment group; least squares mean difference −1.02; 95% confidence limits −2.75, 0.70; p = 0.24). Numerical efficacy advantages for brexpiprazole were observed at other time points. The most common TEAE in the randomised study was akathisia (brexpiprazole, 14.0%; placebo, 1.2%); data from the open-label study (N = 199 analysed) suggested that TEAEs were transient.

The primary endpoint of the randomised study was not met. Further research on brexpiprazole in BPD is warranted based on possible efficacy signals at other time points and its safety profile.

ClinicalTrials.gov identifiers: NCT04100096, NCT04186403. Funding: Otsuka, Lundbeck.

Borderline personality disorder (BPD) is a debilitating condition characterized by pervasive instability across multiple major domains of functioning. The majority of persons with BPD engage in self-injury and up to 10% die by suicide – rendering persons with this condition at exceptionally elevated risk of comorbidity and premature mortality. Better characterization of clinical risk factors among persons with BPD who die by suicide is urgently needed.

We examined patterns of medical and psychiatric diagnoses (1580 to 1700 Phecodes) among persons with BPD who died by suicide (n = 379) via a large suicide death data resource and biobank. In phenotype-based phenome-wide association tests, we compared these individuals to three other groups: (1) persons who died by suicide without a history of BPD (n = 9468), (2) persons still living with a history of BPD diagnosis (n = 280), and (3) persons who died by suicide with a different personality disorder (other PD n = 589).

Multivariable logistic regression models revealed that persons with BPD who died by suicide were more likely to present with co-occurring psychiatric diagnoses, and have a documented history of self-harm in the medical system prior to death, relative to suicides without BPD. Posttraumatic stress disorder was more elevated among those with BPD who died by suicide relative to the other PD group.

We found significant differences among persons with BPD who died by suicide and all other comparison groups. Such differences may be clinically informative for identifying high-risk subtypes and providing targeted intervention approaches.

Neuroimaging studies suggest alterations in prefrontal cortex (PFC) activity in healthy adults under stress. Adolescents with non-suicidal self-injury (NSSI) report difficulties in stress and emotion regulation, which may be dependent on their level of borderline personality disorder (BPD).

The aim was to examine alterations in the PFC in adolescents with NSSI during stress.

Adolescents (13–17 years) engaging in non-suicidal self-injury (n = 30) and matched healthy controls (n = 29) performed a task with low cognitive demand and the Trier Social Stress Test (TSST). Mean PFC oxygenation across the PFC was measured with an eight-channel near-infrared spectroscopy system. Alongside self-reports on affect, dissociation and stress, BPD pathology was assessed via clinical interviews.

Mixed linear-effect models revealed a significant effect of time on PFC oxygenation and a significant time×group interaction, indicating increased PFC activity in patients engaging in NSSI at the beginning of the TSST compared with healthy controls. Greater BPD symptoms overall were associated with an increase in PFC oxygenation during stress. In exploratory analyses, mixed models addressing changes in PFC connectivity over time as a function of BPD symptoms were significant only for the left PFC.

Results indicate differences in the neural stress response in adolescents with NSSI in line with classic neuroimaging findings in adults with BPD. The link between PFC oxygenation and measures of BPD symptoms emphasises the need to further investigate adolescent risk-taking and self-harm across the spectrum of BPD, and maybe overall personality pathology, and could aid in the development of tailored therapeutic interventions.

To examine if the COVID-19 pandemic was associated with a differential effect longitudinally in relation to its psychological and functional impact on patients with bipolar disorder and Emotionally Unstable Personality Disorder (EUPD).

Semi-structured interviews were conducted with 29 individuals attending the Galway-Roscommon Mental Health Services with an ICD-10 diagnosis of either bipolar disorder (n = 18) or EUPD (n = 11). The impact of the COVID-19 pandemic was assessed in relation to anxiety and mood symptoms, social and occupational functioning, and quality of life utilising psychometric instruments and Likert scale data, with qualitative data assessing participants’ subjective experiences.

Individuals with EUPD exhibited significant anxiety and depressive symptoms and increased hopelessness compared to individuals with bipolar disorder. Repeated measures data demonstrated no significant change in symptomatology for either the EUPD or bipolar disorder group over time, but demonstrated an improvement in social (t = 4.40, p < 0.001) and occupational functioning (t = 3.65, p = 0.03), and in quality of life (t = 4.03, p < 0.001) for both participant groups. Themes attained from qualitative data included the positive impact of the discontinuation of COVID-19 mandated restrictions (n = 19), and difficulties experienced secondary to reductions in the provision of mental health services during the COVID-19 pandemic (n = 17).

Individuals with EUPD demonstrated increased symptomatology over a two-year period compared to those with bipolar disorder. The importance of face-to-face mental health supports for this cohort are indicated, particularly if future pandemics impact the delivery of mental health services.

The pain analgesia hypothesis suggests that reduced pain sensitivity (PS) is a specific risk factor for the engagement in non-suicidal self-injury (NSSI). Consistent with this, several studies found reduced PS in adults as well as adolescents with NSSI. Cross-sectional studies in adults with borderline personality disorder (BPD) suggest that PS may (partially) normalize after remission or reduction of BPD symptoms. The objective of the present study was to investigate the development of PS over 1 year in a sample of adolescents with NSSI and to investigate whether PS at baseline predicts longitudinal change in NSSI.

N = 66 adolescents who underwent specialized treatment for NSSI disorder participated in baseline and 1-year follow-up assessments, including heat pain stimulation for the measurement of pain threshold and tolerance. Associations between PS and NSSI as well as BPD and depressive symptoms were examined using negative binomial, logistic, and linear regression analyses.

We found that a decrease in pain threshold over time was associated with reduced NSSI (incident rate ratio = 2.04, p = 0.047) and that higher pain tolerance at baseline predicted lower probability for NSSI (odds ratio = 0.42, p = 0.016) 1 year later. However, the latter effect did not survive Holm correction (p = 0.059). No associations between PS and BPD or depressive symptoms were observed.

Our findings suggest that pain threshold might normalize with a decrease in NSSI frequency and could thus serve as a state marker for NSSI.

Borderline personality disorder (BPD) is a severe psychiatric disorder conceptualised as a disorder of emotion regulation. Emotion regulation has been linked to a frontolimbic network comprising the dorsolateral prefrontal cortex and the amygdala, which apparently synchronises its activity via oscillatory coupling in the theta frequency range.

To analyse whether there are distinct differences in theta oscillatory coupling in frontal brain regions between individuals with BPD and matched controls during emotion regulation by cognitive reappraisal.

Electroencephalogram (EEG) recordings were performed in 25 women diagnosed with BPD and 25 matched controls during a cognitive reappraisal task in which participants were instructed to downregulate negative emotions evoked by aversive visual stimuli. Between- and within-group time–frequency analyses were conducted to analyse regulation-associated theta activity (3.5–8.5 Hz).

Oscillatory theta activity differed between the participants with BPD and matched controls during cognitive reappraisal. Regulation-associated theta increases were lower in frontal regions in the BPD cohort compared with matched controls. Functional connectivity analysis for regulation-associated changes in the theta frequency band revealed a lower multivariate interaction measure (MIM) increase in frontal brain regions in persons with BPD compared with matched controls.

Our findings support the notion of alterations in a frontal theta network in BPD, which may be underlying core symptoms of the disorder such as deficits in emotion regulation. The results add to the growing body of evidence for altered oscillatory brain dynamics in psychiatric populations, which might be investigated as individualised treatment targets using non-invasive stimulation methods.

Psychological treatments for young people with sub-threshold or full-syndrome borderline personality disorder (BPD) are found to be effective. However, little is known about the age at which adolescents benefit from early intervention. This study investigated whether age affects the effectiveness of early intervention for BPD.

N = 626 participants (M age = 15 years, 82.7% female) were consecutively recruited from a specialized outpatient service for early intervention in BPD in adolescents aged 12- to 17-years old. DSM-IV BPD criteria were assessed at baseline, one-year (n = 339) and two-year (n = 279) follow-up.

Older adolescents presented with more BPD criteria (χ2 (1) = 58.23, p < 0.001) and showed a steeper decline of BPD criteria over the 2-year follow-up period compared with younger adolescents (χ2 (2) = 13.53, p = 0.001). In an attempt to disentangle effects of early intervention from the natural course of BPD, a parametrized regression model was used. An exponential decrease (b = 0.10, p < 0.001) in BPD criteria was found when starting therapy over the 2-year follow-up. This deviation from the natural course was impacted by age at therapy commencement (b = 0.06, p < 0.001), although significant across all ages: older adolescents showed a clear decrease in BPD criteria, and young adolescents a smaller decrease.

Early intervention appears effective across adolescence, but manifests differently: preventing the normative increase of BPD pathology expected in younger adolescents, and significantly decreasing BPD pathology in older adolescents. The question as to whether developmentally adapted therapeutic interventions could lead to an even increased benefit for younger adolescents, should be explored in future studies.

The modulation of brain circuits of emotion is a promising pathway to treat borderline personality disorder (BPD). Precise and scalable approaches have yet to be established. Two studies investigating the amygdala-related electrical fingerprint (Amyg-EFP) in BPD are presented: one study addressing the deep-brain correlates of Amyg-EFP, and a second study investigating neurofeedback (NF) as a means to improve brain self-regulation.

Study 1 combined electroencephalography (EEG) and simultaneous functional magnetic resonance imaging to investigate the replicability of Amyg-EFP-related brain activation found in the reference dataset (N = 24 healthy subjects, 8 female; re-analysis of published data) in the replication dataset (N = 16 female individuals with BPD). In the replication dataset, we additionally explored how the Amyg-EFP would map to neural circuits defined by the research domain criteria. Study 2 investigated a 10-session Amyg-EFP NF training in parallel to a 12-weeks residential dialectical behavior therapy (DBT) program. Fifteen patients with BPD completed the training, N = 15 matched patients served as DBT-only controls.

Study 1 replicated previous findings and showed significant amygdala blood oxygenation level dependent activation in a whole-brain regression analysis with the Amyg-EFP. Neurocircuitry activation (negative affect, salience, and cognitive control) was correlated with the Amyg-EFP signal. Study 2 showed Amyg-EFP modulation with NF training, but patients received reversed feedback for technical reasons, which limited interpretation of results.

Recorded via scalp EEG, the Amyg-EFP picks up brain activation of high relevance for emotion. Administering Amyg-EFP NF in addition to standardized BPD treatment was shown to be feasible. Clinical utility remains to be investigated.

Recent findings suggest that brief dialectical behavior therapy (DBT) for borderline personality disorder is effective for reducing self-harm, but it remains unknown which patients are likely to improve in brief v. 12 months of DBT. Research is needed to identify patient characteristics that moderate outcomes. Here, we characterized changes in cognition across brief DBT (DBT-6) v. a standard 12-month course (DBT-12) and examined whether cognition predicted self-harm outcomes in each arm.

In this secondary analysis of 240 participants in the FASTER study (NCT02387736), cognitive measures were administered at pre-treatment, after 6 months, and at 12 months. Self-harm was assessed from pre-treatment to 2-year follow-up. Multilevel models characterized changes in cognition across treatment. Generalized estimating equations examined whether pre-treatment cognitive performance predicted self-harm outcomes in each arm.

Cognitive performance improved in both arms after 6 months of treatment, with no between-arm differences at 12-months. Pre-treatment inhibitory control was associated with different self-harm outcomes in DBT-6 v. DBT-12. For participants with average inhibitory control, self-harm outcomes were significantly better when assigned to DBT-12, relative to DBT-6, at 9–18 months after initiating treatment. In contrast, participants with poor inhibitory control showed better self-harm outcomes when assigned to brief DBT-6 v. DBT-12, at 12–24 months after initiating treatment.

This work represents an initial step toward an improved understanding of patient profiles that are best suited to briefer v. standard 12 months of DBT, but observed effects should be replicated in a waitlist-controlled study to confirm that they were treatment-specific.

Tending to patients with a diagnosis of borderline personality disorder (BPD) is a challenging task for clinicians due to stigma and differences in opinion within the psychiatric community. Various symptoms of BPD including affective instability, mood reactivity, and extremes of idealization are associated with challenging emotions toward patients with BPD. This observational research study utilized an adaptation of the 37-question Attitude to Personality Disorder Questionnaire (APDQ) to assess the attitudes of clinicians toward patients with BPD.

This questionnaire was distributed to 139 clinicians including psychiatry attendings, psychiatry residents, registered nurses, nurse practitioners, social workers, recreation and art therapists, and psychologists who worked with patients diagnosed with BPD on an inpatient unit. Responses of participants were compared based on occupation, gender, and duration of years worked on an inpatient psychiatric unit.

Results show that individuals employed in occupations under the “other health professionals” category had more positive transference (which included feelings of respect toward BPD patients along with feelings of closeness and warmth) toward patients with BPD, and nurses had an increased total score for lack of valid difficulties compared with other health professionals. When grouping by gender and duration of year spent working on an inpatient unit, there were no significant differences in the response toward patients with BPD in affective situations.

Clinical implications are discussed, as well as the need for training to help improve staff attitudes toward this patient population.

There is insufficient evidence to support the pharmacological treatment of borderline personality disorder. However, previous out-patient cohorts have described high rates of polypharmacy in this group. So far, there have been no national studies that have considered polypharmacy in borderline personality disorder.

To describe psychotropic polypharmacy in people with borderline personality disorder in New Zealand.

New Zealand's national databases have been used to link psychotropic medication dispensing data and diagnostic data for borderline personality disorder. Annual dispensing data for 2014 and 2019 have been compared.

Fifty percent of people with borderline personality disorder who were dispensed medications had three or more psychotropic medications in 2014. This increased to 55.9% in 2019 (P < 0.001). Those on seven or more psychotropics increased from 8.4 to 10.7% (P < 0.023). Quetiapine was the most dispensed psychotropic medication, being given to 53.8% of people dispensed medication with borderline personality disorder in 2019. Lorazepam dispensing showed the largest increase, going from 15.5 to 26.7% between 2014 and 2019 (P < 0.001).

There is a large burden of psychotropic polypharmacy in people with borderline personality disorder. This is concerning because of the lack of evidence regarding the efficacy of these medications in this group.