Membrane shape as a reporter for applied forces

Recent advances have enabled 3-dimensional reconstructions of biological structures in vivo, ranging in size and complexity from single proteins to multicellular structures. In particular, tomography and confocal microscopy have been exploited to capture detailed 3-dimensional conformations of membranes in cellular processes ranging from viral budding and organelle maintenance to phagocytosis. Despite the wealth of membrane structures available, there is as yet no generic, quantitative method for their interpretation. We propose that by modeling these observed biomembrane shapes as fluid lipid bilayers in mechanical equilibrium, the externally applied forces as well as the pressure, tension, and spontaneous curvature can be computed directly from the shape alone. To illustrate the potential power of this technique, we apply an axial force with optical tweezers to vesicles and explicitly demonstrate that the applied force is equal to the force computed from the membrane conformation

A Model of Trust Processes in Borderline Personality Disorder: A Systematic Review

Purpose of Review: Unstable relationships are a core feature of borderline personality disorder (BPD). Impairments in trust processes (i.e., appraisal and learning regarding others’ trustworthiness) can subserve interpersonal problems associated with BPD, but the determinants, mechanisms, consequences, and variations in trust impairments among individuals with BPD remain poorly characterized. Thus, a better understanding of such impairments could help target interventions that address the interpersonal problems of individuals with BPD beyond emotion dysregulation, impulsivity, and aggression. Recent Findings: We conducted a pre-registered systematic review of empirical studies on trust processes and BPD features (k = 29). Results are organized around a heuristic model of trust processes in BPD comprising the following stages: developmental factors, prior beliefs and dispositions, situation perception, emotional states, trust appraisal, behavioral manifestations, and trust learning. Summary: Based on the synthesis of the findings, we recommended directions for future research and clinical assessment and intervention, such as managing trust during the early stages of therapy and considering improvements in trust processes as a central mechanism of change in treating individuals with BPD

Endogenous oxytocin is associated with the experience of compassion and recalled upbringing in Borderline Personality Disorder

Background/Objective The role of the neuropeptide oxytocin (OT) in Borderline Personality Disorder (BPD) is poorly understood. It is particularly unknown how early experiences with caregivers moderate the action of OT in BPD. Here, we examined the association of plasma OT levels in BPD patients with the experience of compassion and recalled parental behavior during childhood. Methods Fifty-seven BPD patients and 43 healthy controls participated in the study. OT plasma levels were analyzed by radioimmunoassay. Subjects additionally completed questionnaires focusing on fears of compassion (FOC) and recalled upbringing (“Questionnaire of Recalled Parental Rearing Behavior/Fragebogen zum erinnerten elterlichen Erziehungsverhalten,” FEE). Results BPD patients had significantly lower OT plasma levels than healthy controls and differed significantly on all FOC and FEE scales; BPD patients had higher FOC scores (indicating more aversion of being compassionate to themselves and others and receiving compassion from others). They also differed in recalled parenting. In the BPD group, scores of the FOC scale “fear of compassion from others” were significantly negatively correlated with OT levels. Moreover, recalled “emotional warmth” of their parents during childhood was positively correlated with OT plasma levels of BPD subjects. No such correlations were found in the control group. Conclusion Our results corroborate findings from previous studies reporting lower OT levels in patients with BPD. Moreover, peripheral OT seems to be linked with the tolerance of compassionate feelings and early experiences with caregivers. This is consistent with other findings that OT is an important mediator of the experience of emotional warmth from others.N/

Reflective function as a mediator between childhood adversity, personality disorder and symptom distress

A growing body of literature has indicated the central role of childhood adversity for the development in later life of personality disorder (PD) and psychiatric distress. In this investigation, we examine the role of reflective function (RF) as a mediator between childhood adversity, subsequent development of PD and psychiatric morbidity. We tested the hypothesis that adversity leads to decreased RF, which in turn is associated with PD, and both increase the likelihood of psychiatric distress. The study sample consisted of 234 individuals, drawn from a clinical PD group (n = 112) and one demographically matched non-psychiatric group (n = 122) using a shared battery of measures, which included the Structured Clinical Interview for DSM-IV, the Symptom Checklist-90-R and the Adult Attachment Interview, which was used to assess RF levels. The results indicated that childhood adversity predicted low level of RF, which in turn was associated with PD onset later in life. A combination of different early adverse experiences had a significantly greater impact on lowering RF scores than experiencing either neglect or abuse alone. Mediation analyses confirmed that RF was a significant mediator between adversity and PD diagnoses and between adversity and psychiatric distress. Copyright © 2013 John Wiley & Sons, Ltd

Membrane curvature at a glance

Membrane curvature is an important parameter in defining the morphology of cells, organelles and local membrane subdomains. Transport intermediates have simpler shapes, being either spheres or tubules. The generation and maintenance of curvature is of central importance for maintaining trafficking and cellular functions. It is possible that local shapes in complex membranes could help to define local subregions. In this Cell Science at a Glance article and accompanying poster, we summarize how generating, sensing and maintaining high local membrane curvature is an active process that is mediated and controlled by specialized proteins using general mechanisms: (i) changes in lipid composition and asymmetry, (ii) partitioning of shaped transmembrane domains of integral membrane proteins or protein or domain crowding, (iii) reversible insertion of hydrophobic protein motifs, (iv) nanoscopic scaffolding by oligomerized hydrophilic protein domains and, finally, (v) macroscopic scaffolding by the cytoskeleton with forces generated by polymerization and by molecular motors. We also summarize some of the discoveries about the functions of membrane curvature, where in addition to providing cell or organelle shape, local curvature can affect processes like membrane scission and fusion as well as protein concentration and enzyme activation on membranes

The Specificity of Mental Pain in Borderline Personality Disorder Compared to Depressive Disorders and Healthy Controls

Background: Individuals with Borderline Personality Disorder (BPD) may experience a qualitatively distinct depression which includes “mental pain.” Mental pain includes chronic, aversive emotions, negative self-concept, and a sense of pervasive helplessness. The present study investigated whether mental pain is elevated in BPD compared to Depressive Disorders (DD) without BPD. Methods: The Orbach and Mikulincer Mental Pain Scale (OMMP) was administered to BPD (N = 57), DD (N = 22), and healthy controls (N = 31). The OMMP assesses total mental pain, comprised of nine subtypes: irreversibility, loss of control, narcissistic wounds, emotional flooding, freezing, self-estrangement, confusion, social distancing, and emptiness. Co-occurring psychiatric diagnoses, depression severity, and other potentially confounding clinical and demographic variables were also assessed. Results: The total Mental Pain score did not differentiate BPD from DD. Moreover, most of the subscales of the OMMP were not significantly different in BPD compared to DD. However, the elevation of mental pain subscale “narcissistic wounds,” characterized by feeling rejected and having low self-worth, was a specific predictor of BPD status and the severity of BPD symptoms. Conclusion: On OMMP total score, mental pain was similarly elevated in BPD and DD. However, the narcissistic wounds sub-type of mental pain was a sensitive and specific diagnostic indicator of BPD and, therefore, may be an important aspect of BPD in need of increased focus in assessment and theoretical models

Rejection Distress Suppresses Medial Prefrontal Cortex in Borderline Personality Disorder

BACKGROUND: Borderline personality disorder (BPD) is characterized by an elevated distress response to social exclusion (i.e., rejection distress), the neural mechanisms of which remain unclear. Functional magnetic resonance imaging studies of social exclusion have relied on the classic version of the Cyberball task, which is not optimized for functional magnetic resonance imaging. Our goal was to clarify the neural substrates of rejection distress in BPD using a modified version of Cyberball, which allowed us to dissociate the neural response to exclusion events from its modulation by exclusionary context. METHODS: Twenty-three women with BPD and 22 healthy control participants completed a novel functional magnetic resonance imaging modification of Cyberball with 5 runs of varying exclusion probability and rated their rejection distress after each run. We tested group differences in the whole-brain response to exclusion events and in the parametric modulation of that response by rejection distress using mass univariate analysis. RESULTS: Although rejection distress was higher in participants with BPD (F1,40 = 5.25, p = .027, η2 = 0.12), both groups showed similar neural responses to exclusion events. However, as rejection distress increased, the rostromedial prefrontal cortex response to exclusion events decreased in the BPD group but not in control participants. Stronger modulation of the rostromedial prefrontal cortex response by rejection distress was associated with higher trait rejection expectation, r = −0.30, p = .050. CONCLUSIONS: Heightened rejection distress in BPD might stem from a failure to maintain or upregulate the activity of the rostromedial prefrontal cortex, a key node of the mentalization network. Inverse coupling between rejection distress and mentalization-related brain activity might contribute to heightened rejection expectation in BPD

How do mothers with borderline personality disorder mentalize when interacting with their infants?

Mothers with borderline personality disorder (BPD) have been theorized to have decreased mentalization ability, which is the capacity to perceive and interpret mental states. This could increase the risk for troubled relationships with their infants and therefore have adverse consequences for child social and emotional development. Mind-mindedness (MM), which codes the mother's references to her infant's mental states during an interaction, is one method of indexing mothers' mentalizing ability. However, research has yet to examine MM in mothers with BPD. Our objective was to assess the MM ability of 38 mothers during interactions with their 12-month-old infants, including 10 mothers with BPD and 28 mothers without a psychiatric diagnosis. Trained observers assessed maternal MM from 2 min of videotaped mother-infant free play. BPD was assessed with the Structured Clinical Interview for DSM-III-R-Personality Disorders (SCID-II). Mothers with and without BPD did not differ in the proportion of total comments referring to infant mental states. However, mothers in the BPD group proportionately made 3.6 times more misattuned mind-related comments than control mothers. Thus, mothers with and without BPD appear equally likely to envision mental states in their infants. However, mothers with BPD also appear more likely to misread their infants' mental states