Alzheimer’s disease-associated peptide Aβ₄₂ mobilizes ER Ca²⁺ via InsP₃R-dependent and -independent mechanisms

Dysregulation of Ca2+ homeostasis is considered to contribute to the toxic action of the Alzheimer’s Disease (AD) associated Amyloid β-peptide (Aβ). Ca2+ fluxes across the plasma membrane and release from intracellular stores have both been reported to underlie the Ca2+ fluxes induced by Aβ42. Here, we investigated the contribution of Ca2+ release from the endoplasmic reticulum (ER) to the effects of Aβ42 upon Ca2+ homeostasis and the mechanism by which Aβ42 elicited these effects. Consistent with previous reports, application of soluble oligomeric forms of Aβ42 exhibited Ca2+ mobilizing properties. The Aβ42-stimulated Ca2+ signals persisted in the absence of extracellular Ca2+ indicating a significant contribution of Ca2+ release from the ER Ca2+ store to the generation of these signals. Moreover, inositol 1,4,5-trisphosphate (InsP3) signaling contributed to Aβ42-stimulated Ca2+ release. The Ca2+ mobilizing effect of Aβ42 was also observed when applied to permeabilized cells deficient in InsP3 receptors revealing an additional direct effect of internalized Aβ42 upon the ER, and a mechanism for induction of toxicity by intracellular Aβ42

Reconciling Psychoanalytic Ideas with Attachment Theory

The relationship between attachment theory and psychoanalysis, historically, has not been an easy one (Cassidy & Shaver, 2008; Eagle, 2013; Fonagy, 2001). But in recent years, developments in both fields have led to a growing rapprochement (Eagle, 2013; Holmes, 2009). Changes in psychoanalytic thinking have made it more accommodating of attachment thinking; conversely, aspects of the development of attachment findings, applications, and theory have made it more pertinent to psychoanalysis. In this chapter we examine the disagreements between psychoanalysis and attachment theory, and point to some of the two disciplines’ common foundations. We then describe an approach to the role of attachment in human development that considers it in relation to the capacity to mentalize, that is, to understand ourselves and others in terms of intentional mental states, and places both attachment and mentalizing in the context of the development of epistemic trust—the capacity to trust others as a source of knowledge about the world. This approach builds on some of Bowlby’s assumptions drawn from evolutionary biology, placing some of the better founded psychoanalytic criticisms of attachment theory in a different perspective. We suggest that this context allows the ongoing significance of Bowlby and Ainsworth’s thinking for the psychoanalytic project to be appreciated

The mentalizing approach to psychopathology: State of the art and future directions

Mentalizing is the capacity to understand others and oneself in terms of internal mental states. It is assumed to be underpinned by four dimensions: automatic–controlled, internally–externally focused, self–other, and cognitive–affective. Research suggests that mental disorders are associated with different imbalances in these dimensions. Addressing the quality of mentalizing as part of psychosocial treatments may be helpful for individuals with various mental disorders. We suggest that mentalizing is a helpful transtheoretical and transdiagnostic concept explaining vulnerability to psychopathology and its treatment. This review summarizes the mentalizing approach to psychopathology from a developmental socioecological evolutionary perspective. We then focus on the application of the mentalizing approach to personality disorders, and review studies that have extended this approach to other types of psychopathology, including depression, anxiety, and eating disorders. We summarize core principles of mentalization-based treatments and preventive interventions, and the evidence for their effectiveness. We conclude with recommendations for future research

Mentalizing, epistemic trust and the phenomenology of psychotherapy

This paper seeks to elucidate the phenomenological experience of psychotherapy in the context of the theory of mentalizing and epistemic trust. We describe two related phenomenological experiences that are the domain of psychotherapeutic work. The first is the patient’s direct experience of their own personal narrative being recognised, marked and reflected back to them by the therapist. Secondly, this intersubjective recognition makes possible the regulation and alignment of the patient’s imaginative capacity in relation to our phenomenological experiences. In describing three aspects of the communication process that unfold in effective psychotherapeutic interventions – 1) the epistemic match, 2) improving mentalizing, and 3) the re-emergence of social learning – the way in which any effective treatment is embedded in metacognitive processes about the self in relation to perceptual social reality is explained. In particular, attention is drawn to wider social determinants of psychopathology. We discuss the possible mechanism for the relationship between the social-economic environment and psychopathology, and the implications of this for psychotherapeutic treatment

The LuckyCam Survey for Very Low Mass Binaries II: 13 new M4.5-M6.0 Binaries

We present results from a high-angular-resolution survey of 78 very low mass (VLM) binary systems with 6.0 = 0.15 arcsec/yr. 21 VLM binaries were detected, 13 of them new discoveries. The new binary systems range in separation between 0.18 arcsec and 1.3 arcsec. The distance-corrected binary fraction is 13.5% (+6.5%/-4%), in agreement with previous results. 9 of the new binary systems have orbital radii > 10 AU, including a new wide VLM binary with 27 AU projected orbital separation. One of the new systems forms two components of a 2300 AU separation triple system. We find that the orbital radius distribution of the binaries with V-K < 6.5 in this survey appears to be different from that of redder (lower-mass) objects, suggesting a possible rapid change in the orbital radius distribution at around the M5 spectral type. The target sample was also selected to investigate X-ray activity among VLM binaries. There is no detectable correlation between excess X-Ray emission and the frequency and binary properties of the VLM systems.Comment: 11 pages, 8 figures. Submitted to MNRA

Self–other distinction and borderline personality disorder features: Evidence for egocentric and altercentric bias in a self–other facial morphing task

Self–other distinction (SOD) refers to the ability to distinguish one’s own body, actions, and mental representations from those of others. Problems with SOD are considered to be a key feature of borderline personality disorder (BPD). However, empirical studies on SOD in BPD are scarce. Here, we present a study providing preliminary support for the usefulness and validity of a self–other facial morphing task to capture the capacity for SOD in a sample of nonclinical participants high (n = 30) and low (n = 32) in BPD features. Participants had to watch a video sequence in which their own face was gradually morphed into the face of an unfamiliar other (self-to-other) or vice versa (other-to-self), requiring them to indicate at which point they judged the morph to look more like the target face than the starting face. Consistent with predictions, results showed that participants in the high-BPD group judged the morph to look like themselves for longer in the self-to-other direction (suggestive of egocentric bias), but only with a relatively more attractive target face. In the other-to-self direction, the high-BPD group had more difficulty recognizing their own face (i.e., an altercentric bias), but this time only with the relatively less attractive face. Further research is needed to replicate these findings in clinical samples, but overall they suggest that the current task might be suited to investigate SOD problems in BPD. (PsycInfo Database Record (c) 2020 APA, all rights reserved

Dynamic interpersonal therapy for moderate to severe depression: A pilot randomized controlled and feasibility trial

Background: Improving Access to Psychological Therapies (IAPT) services treat most patients in England who present to primary care with major depression. Psychodynamic psychotherapy is one of the psychotherapies offered. Dynamic Interpersonal Therapy (DIT) is a psychodynamic and mentalization-based treatment for depression. 16 sessions are delivered over approximately 5 months. Neither DIT's effectiveness relative to low-intensity treatment (LIT), nor the feasibility of randomizing patients to psychodynamic or cognitive-behavioural treatments (CBT) in an IAPT setting has been demonstrated. Methods: 147 patients were randomized in a 3:2:1 ratio to DIT (n = 73), LIT (control intervention; n = 54) or CBT (n = 20) in four IAPT treatment services in a combined superiority and feasibility design. Patients meeting criteria for major depressive disorder were assessed at baseline, mid-treatment (3 months) and post-treatment (6 months) using the Hamilton Rating Scale for Depression (HRSD-17), Beck Depression Inventory-II (BDI-II) and other self-rated questionnaire measures. Patients receiving DIT were also followed up 6 months post-completion. Results: The DIT arm showed significantly lower HRSD-17 scores at the 6-month primary end-point compared with LIT (d = 0.70). Significantly more DIT patients (51%) showed clinically significant change on the HRSD-17 compared with LIT (9%). The DIT and CBT arms showed equivalence on most outcomes. Results were similar with the BDI-II. DIT showed benefit across a range of secondary outcomes.ConclusionsDIT delivered in a primary care setting is superior to LIT and can be appropriately compared with CBT in future RCTs