A pilot randomized controlled trial of ketamine in Borderline Personality Disorder.

This study is the first randomized controlled trial to test the effects of ketamine in Borderline Personality Disorder (BPD). BPD remains undertreated in the community and no medication has FDA approval for this indication. People with BPD experience chronic mood disturbances with depressed mood, suicidal ideation, and severe social difficulties. In this double-blind, randomized controlled pilot study, we tested the effects of one infusion of ketamine (0.5 mg/kg, n = 10) or the psychoactive comparator drug midazolam (0.04 mg/kg, n = 12) in adults with BPD. Infusions were well tolerated in both groups. Dissociative symptoms during infusion were more intense with ketamine than midazolam (t(12.3) = 3.61, p = 0.01), but they resolved by 40 min after infusion in both groups. Post-infusion adverse events were at the expected low levels in both groups. For our primary outcome measure of suicidal ideation and our secondary outcome measure of depression, we found numerical reduction but not significant group or group x timepoint difference (p > 0.05). For our secondary outcome measures of anxiety and BPD symptoms, we did not observe group or group x timepoint differences. There was a group x timepoint effect for socio-occupational functioning (F(1,20.12) = 5.16, p = 0.03, at Day 14, ketamine group showed more improvement than midazolam group). An exploratory analysis revealed that improvement in socio-occupational functioning was correlated with improvement in depression in the ketamine group (r(8) = 0.65, p = 0.04) but not midazolam group (r(9) = 0.41, p = 0.216). This pilot study provides the first randomized controlled evidence of the effects of antidepressant-dosed ketamine in people with BPD. Our results provide reason for optimism that antidepressant-dosed ketamine will be well-tolerated in larger studies and may provide clinical benefit for mood symptoms and related impairments in people with BPD.

Mentalization and embodied selfhood in Borderline Personality Disorder.

Aberrations of self-experience are considered a core feature of Borderline Personality Disorder (BPD). While prominent etiologic accounts of BPD, such as the mentalization based approach, appeal to the developmental constitution of self in early infant-caregiver environments, they often rely on a conception of self that is not explicitly articulated. Moreover, self-experience in BPD is often theorized at the level of narrative identity, thus minimizing the role of embodied experience. In this article, we present the hypothesis that disordered self and interpersonal functioning in BPD result, in part, from impairments in "embodied mentalization," that manifest foundationally as alterations in minimal embodied selfhood, i.e. the first-person experience of being an individuated embodied subject. This account of BPD, which engages early intersubjective experiences has the potential to integrate phenomenological, developmental, and symptomatic findings in BPD, and is consistent with contemporary theories of brain function.

Practical Tips for Implementing a Student-Led Reflective Writing Workshop Series.

Reflective practice may ameliorate the burnout, empathy loss, and depression that medical students experience during clerkships. We describe a student-led reflective writing workshop in a safe and structured small group setting. We provide twelve tips for implementing such a workshop, informed by the existing literature on reflective writing and near-peer teaching, which include developing writing prompts, guiding student facilitators, and obtaining feedback. Common topics include patient suffering, workplace dynamics, and the joys of practicing medicine. Participants develop camaraderie with peers as well as tools they can carry forward as they continue to process the challenging experiences intrinsic to clinical medicine.

Induced illusory body ownership in borderline personality disorder.

One aspect of selfhood that may have relevance for borderline personality disorder (BPD) is variation in sense of body ownership. We employed the rubber hand illusion to manipulate sense of body ownership in BPD. We extended previous research on illusory body ownership in BPD by testing: (i) two illusion conditions: asynchronous and synchronous stimulation, (ii) relationship between illusion experience and BPD symptoms, and (iii) relationship between illusion experience and maladaptive personality traits. We measured illusion strength (questionnaire responses), proprioceptive drift (perceived shift in physical hand position), BPD symptoms (Revised Diagnostic Interview for Borderlines score), and maladaptive personality traits (Personality Inventory for DSM-5) in 24 BPD and 21 control participants. For subjective illusion strength, we found main effects of group (BPD > healthy control, F(1, 43) = 11.94, P = 0.001) and condition (synchronous > asynchronous, F(1, 43) = 22.80, P < 0.001). There was a group × condition interaction for proprioceptive drift (F(1, 43) = 6.48, P = 0.015) such that people with BPD maintained illusion susceptibility in the asynchronous condition. Borderline symptom severity correlated with illusion strength within the BPD group, and this effect was specific to affective (r = 0.45, P < 0.01) and cognitive symptoms (r = 0.46, P < 0.01). Across all participants, trait psychoticism correlated with illusion strength (r = 0.44, P < 0.01). People with BPD are more susceptible to illusory body ownership than controls. This is consistent with the clinical literature describing aberrant physical and emotional experiences of self in BPD. A predictive coding framework holds promise to develop testable mechanistic hypotheses for disrupted bodily self in BPD.

Individuals with Borderline Personality Disorder show larger preferred social distance in live dyadic interactions.

Personal space regulation is a key component of effective social engagement. Personal space varies among individuals and with some mental health conditions. Simulated personal space intrusions in Borderline Personality Disorder (BPD) reveal larger preferred interpersonal distance in that setting. These findings led us to conduct the first test of live interpersonal distance preferences in symptoms in BPD. With direct observation of subjects' personal space behavior in the stop-distance paradigm, we found a 2-fold larger preferred interpersonal distance in BPD than control (n = 30, n = 23). We discuss this result in context of known biology and etiology of BPD. Future work is needed to identify neural circuits underlying personal space regulation in BPD, individual differences in preferred interpersonal distance in relation to specific symptoms and relationship to recovery status.

Metastatic Colorectal Cancer: A Systematic Review of the Value of Current Therapies.

To evaluate, from a US payer perspective, the cost-effectiveness of treatment strategies for metastatic colorectal cancer (mCRC), we performed a systematic review of published cost-effectiveness analyses. We identified 14 papers that fulfilled our search criteria and revealed varying levels of value among current treatment strategies. Older agents such as 5-fluorouracil, irinotecan, and oxaliplatin provide high-value treatments. More modern agents targeting the EGFR or VEGF pathways, such as bevacizumab, cetuximab, and panitumumab, do not appear to be cost-effective treatments at their current costs. The analytical methods used within the papers varied widely, and this variation likely plays a significant role in the heterogeneity in incremental cost-effectiveness ratios. The cost-effectiveness of current treatment strategies for mCRC is highly variable. Drugs recently approved by the US Food and Drug Administration for mCRC are not cost-effective, and this is primarily driven by high drug costs.

Is prevention a realistic goal for schizophrenia?

Over the past 2 decades, increased efforts have focused on identifying those at genetic or clinical risk for psychosis and promoting interventions that may alter the onset or trajectory of schizophrenia. We review studies published between 2010-2013 that: (1) investigate at-risk states for psychosis in larger epidemiological studies; (2) identify causes of certain clinical presentations of the schizophrenia phenotype and (3) investigate focused and multidisciplinary approaches to treat early clinical symptoms. The article places these recent studies within the context of prior research and the concept of potential measures to prevent or ameliorate the onset of psychosis.