Narcissistic personality disorder in the ICD-11: Severity and trait profiles of grandiosity and vulnerability.

Modern diagnostic and classification frameworks such as the ICD-11 and DSM-5-AMPD have adopted a dimensional approach to diagnosing personality disorder using a dual "severity" and "trait" model. As narcissistic personality has historically struggled to be adequately captured in dominant diagnostic systems, this study investigated the utility of the new ICD-11 framework in capturing diverse narcissistic expressions. Participants were mental health clinicians (N = 180, 67% female, age = 38.9), who completed ratings of ICD-11 personality severity, trait domains and a clinical reflection for two hypothetical case vignettes reflecting either prototypical "grandiose" or "vulnerable" narcissism. The majority of clinicians (82%) endorsed a diagnosis of personality disorder for both grandiose and vulnerable vignettes. Discriminant elements of personality impairment included rigid, unrealistically positive self-view, low empathy and high conflict with others for grandiosity, and incoherent identity, low self-esteem and hypervigilant, avoidant relations with others for vulnerability. Regarding trait profile, grandiose narcissism was predominately dissocial whereas vulnerable narcissism was primarily associated with negative affectivity and detachment. Qualitative responses highlight distinct clinical themes for each presentation. These findings suggest that clinicians using the ICD-11 framework are able to identify common core elements of personality dysfunction in grandiose and vulnerable narcissism while also recognizing their distinctive differences.

A Split-Lung Ex Vivo Perfusion Model for Time- and Cost-Effective Evaluation of Therapeutic Interventions to the Human Donor Lung.

With the ongoing shortage of donor lungs, ex vivo lung perfusion (EVLP) offers the opportunity for objective assessment and potential therapeutic repair of marginal organs. There is a need for robust research on EVLP interventions to increase the number of transplantable organs. The use of human lungs, which have been declined for transplant, for these studies is preferable to animal organs and is indeed essential if clinical translation is to be achieved. However, experimental human EVLP is time-consuming and expensive, limiting the rate at which promising interventions can be assessed. A split-lung EVLP model, which allows stable perfusion and ventilation of two single lungs from the same donor, offers advantages scientifically, financially and in time to yield results. Identical parallel circuits allow one to receive an intervention and the other to act as a control, removing inter-donor variation between study groups. Continuous hemodynamic and airway parameters are recorded and blood gas, perfusate, and tissue sampling are facilitated. Pulmonary edema is assessed directly using ultrasound, and indirectly using the lung tissue wet:dry ratio. Evans blue dye leaks into the tissue and can quantify vascular endothelial permeability. The split-lung ex vivo perfusion model offers a cost-effective, reliable platform for testing therapeutic interventions with relatively small sample sizes.

Transventricular Cardioscopic Release of a Trapped Prosthetic Mitral Valve Leaflet.

Trapped prosthetic valve leaflets are a rare but challenging complication. A 68-year-old male patient had previously undergone redo aortic valve replacement. Postoperatively, he decompensated with severe mitral regurgitation, requiring extracorporeal membrane oxygenation and a salvage mitral valve replacement via right thoracotomy with very difficult access. This procedure was complicated by a trapped valve leaflet. He recovered well initially but presented 2 years later with worsening heart failure due to mitral stenosis and rising pulmonary artery pressures. Due to the high risk of sternotomy and right thoracotomy, a transventricular cardioscopic release of the trapped mitral valve leaflet was undertaken by left minithoracotomy. The procedure was successful, and the patient was discharged home on day 12. This novel minimally invasive approach, which does not require myocardial preservation, is ideal for high-risk patients with this rare complication and has not previously been described. We hope that by sharing our experience, others will consider this innovative approach.

"It's not you, it's me": identity disturbance as the main contributor to interpersonal problems in pathological narcissism.

BACKGROUND: Core impairments in self and other functioning typify individuals with personality disorder. While interpersonal dysfunction is a known element of narcissistic disorders, empirical research investigating intrapersonal elements is lacking. The aim of this study was to investigate the internal representations of individuals with grandiose and vulnerable features, as manifested through their attachment styles, and the specific role of identity disturbance in explaining the relationship between pathological narcissism and maladaptive interpersonal functioning. METHODS: A sample of 270 university students completed the Brief Pathological Narcissism Inventory (B-PNI), the Severity Indices of Personality Problems (SIPP), the Relationship Questionnaire (RQ), and the Inventory of Interpersonal Problems (IIP-32). RESULTS: Both vulnerable and grandiose narcissism were positively associated with both fearful and preoccupied attachment, and negatively associated with secure attachment, whilst grandiose narcissism was also positively associated with dismissive attachment. Furthermore, unstable representations of self, poor self-reflective functioning, and low sense of purpose fully mediated the relationship between interpersonal problems and grandiose narcissism while partially mediating the relationship between interpersonal problems and vulnerable narcissism. CONCLUSIONS: Overall, our findings suggest that for individuals presenting with narcissistic features, capacity for adaptive interpersonal functioning is grounded by deficits in identity integration. Implications of these findings are discussed.

Living with pathological narcissism: core conflictual relational themes within intimate relationships.

BACKGROUND: Pathological narcissism is a severe mental health condition that includes disturbances in interpersonal functioning. Interpersonal difficulties by those affected include aggressive, domineering, cold and coercive behaviours which often result in strong negative reactions from others. We sought to examine the moment-to-moment patterns that emerge within close relationships between intimate partners and family members. METHODS: Participants (N = 15) were romantic partners (73.3%) and family members (26.6%) in a close and long-term relationship (+ 10 years) with an individual with pathological narcissism. Participants told verbatim relationship narratives involving five narrative interactions with their relative with pathological narcissism and five narrative interactions with others. Transcripts were coded using the using Core Conflictual Relationship Theme method. Participants also completed three versions of the Relationship Questionnaire, reporting on 1. their relationship style 'in general', 2. their relationship style 'with their relative' and 3. the relationship style of their relative. RESULTS: A total of 133 relationship episodes were analysed, comprising 783 components (wishes, responses of others and responses of self). While the identified wishes (e.g., for love, for support) were consistent between relative and non-relative narratives, there was significantly higher disharmony and lower harmony in narratives involving relatives with pathological narcissism. Described disharmony in these relationships involved the relative's rejecting, subjugating and attacking behaviours, and participants rejecting and withdrawing behaviours. There was a prominent deactivation of participants attachment system when interacting with their relative with pathological narcissism, endorsing predominately dismissing relationship styles. Individuals with pathological narcissism were similarly rated as predominately dismissing. CONCLUSIONS: Together, these results reflect the cycles of interpersonal dysfunction for individuals with pathological narcissism and their partners and family members. Treatment implications point to the risk of therapists withdrawing and dismissing a patient with high pathological narcissism in the countertransference. Strategies to monitor and manage these core relational themes in treatment remain a challenge.

Pathological narcissism: An analysis of interpersonal dysfunction within intimate relationships.

Pathological narcissism is marked by deficits in psychosocial functioning. Difficulties in relationships include instances of aggression, devaluation and control; however, few studies have examined these relationships from the perspective of partners and family members. We studied participants who were in relationships with relatives high in narcissistic traits (N = 436; current romantic partners [57.3%]; former romantic partners [21.1%]; family members [15.4%]). Participant responses were analysed thematically, and their underlying mental health problems were also measured. Thematic analysis of participant responses indicated themes of abuse from the relative with narcissism (physical, verbal, emotional and sexual) as well as the relative imposing challenging financial and sexual behaviours. There were complex interpersonal themes of mutual idealization but also devaluation. In response, participants reported high levels of anxiety, depression, self-aggression, sickness and somatic concerns. Further, participants expressed overt outward hostility towards their relative with narcissism, but also dependency strivings and frustrated dependency themes. Partners and their relative with narcissism appeared locked into interpersonal and intrapersonal dynamic conflicts. Clinical implications include specific attendance to alliance issues, dependency themes, and a focus on limit setting to establish personal safety.

Living with pathological narcissism: a qualitative study.

Background: Research into the personality trait of narcissism have advanced further understanding of the pathological concomitants of grandiosity, vulnerability and interpersonal antagonism. Recent research has established some of the interpersonal impacts on others from being in a close relationship with someone having such traits of pathological narcissism, but no qualitative studies exist. Individuals with pathological narcissism express many of their difficulties of identity and emotion regulation within the context of significant interpersonal relationships thus studying these impacts on others is warranted. Method: We asked the relatives of people high in narcissistic traits (indexed by scoring above a cut-off on a narcissism screening measure) to describe their relationships (N = 436; current romantic partners [56.2%]; former romantic partners [19.7%]; family members [21.3%]). Participants were asked to describe their relative and their interactions with them. Verbatim responses were thematically analysed. Results: Participants described 'grandiosity' in their relative: requiring admiration, showing arrogance, entitlement, envy, exploitativeness, grandiose fantasy, lack empathy, self-importance and interpersonal charm. Participants also described 'vulnerability' of the relative: contingent self-esteem, hypersensitivity and insecurity, affective instability, emptiness, rage, devaluation, hiding the self and victimhood. These grandiose and vulnerable characteristics were commonly reported together (69% of respondents). Participants also described perfectionistic (anankastic), vengeful (antisocial) and suspicious (paranoid) features. Instances of relatives childhood trauma, excessive religiosity and substance abuse were also described. Conclusions: These findings lend support to the importance of assessing the whole dimension of the narcissistic personality, as well as associated personality patterns. On the findings reported here, the vulnerable aspect of pathological narcissism impacts others in an insidious way given the core deficits of feelings of emptiness and affective instability. These findings have clinical implications for diagnosis and treatment in that the initial spectrum of complaints may be misdiagnosed unless the complete picture is understood. Living with a person with pathological narcissism can be marked by experiencing a person who shows large fluctuations in affect, oscillating attitudes and contradictory needs.

Measuring the shadows: A systematic review of chronic emptiness in borderline personality disorder.

BACKGROUND: Chronic feelings of emptiness is an under-researched symptom of borderline personality disorder (BPD), despite indications it may be central to the conceptualisation, course, and outcome of BPD treatment. This systematic review aimed to provide a comprehensive overview of chronic feelings of emptiness in BPD, identify key findings, and clarify differences between chronic feelings of emptiness and related constructs like depression, hopelessness, and loneliness. METHOD: A PRISMA guided systematic search of the literature identified empirical studies with a focus on BPD or BPD symptoms that discussed chronic feelings of emptiness or a related construct. RESULTS: Ninety-nine studies met criteria for inclusion in the review. Key findings identified there were significant difficulties in defining and measuring chronic emptiness. However, based on the studies reviewed, chronic emptiness is a sense of disconnection from both self and others. When experienced at frequent and severe levels, it is associated with low remission for people with BPD. Emptiness as a construct can be separated from hopelessness, loneliness and intolerance of aloneness, however more research is needed to explicitly investigate these experiences. Chronic emptiness may be related to depressive experiences unique to people with BPD, and was associated with self-harm, suicidality, and lower social and vocational function. CONCLUSIONS AND IMPLICATIONS: We conclude that understanding chronic feelings of emptiness is central to the experience of people with BPD and treatment focusing on connecting with self and others may help alleviate a sense of emptiness. Further research is required to provide a better understanding of the nature of chronic emptiness in BPD in order to develop ways to quantify the experience and target treatment. Systematic review registration number: CRD42018075602.

Metabolic Fingerprinting Links Oncogenic PIK3CA with Enhanced Arachidonic Acid-Derived Eicosanoids.

Oncogenic transformation is associated with profound changes in cellular metabolism, but whether tracking these can improve disease stratification or influence therapy decision-making is largely unknown. Using the iKnife to sample the aerosol of cauterized specimens, we demonstrate a new mode of real-time diagnosis, coupling metabolic phenotype to mutant PIK3CA genotype. Oncogenic PIK3CA results in an increase in arachidonic acid and a concomitant overproduction of eicosanoids, acting to promote cell proliferation beyond a cell-autonomous manner. Mechanistically, mutant PIK3CA drives a multimodal signaling network involving mTORC2-PKCζ-mediated activation of the calcium-dependent phospholipase A2 (cPLA2). Notably, inhibiting cPLA2 synergizes with fatty acid-free diet to restore immunogenicity and selectively reduce mutant PIK3CA-induced tumorigenicity. Besides highlighting the potential for metabolic phenotyping in stratified medicine, this study reveals an important role for activated PI3K signaling in regulating arachidonic acid metabolism, uncovering a targetable metabolic vulnerability that largely depends on dietary fat restriction. VIDEO ABSTRACT.

Pathological Narcissism: A Study of Burden on Partners and Family.

Pathological narcissism is characterized by impaired interpersonal functioning, but few studies have examined the impact of the disorder on those living in a close relationship. Participants (N = 683; comprising romantic partners [77.8%], mothers [8.5%] or other family members [10%]) in a close relationship with a relative with pathological narcissism completed measures assessing levels of grief, burden, mental health, and coping style. Participants' reported burden was over 1.5 standard deviations above comparison carers of people with mood, neurotic, or psychotic disorders, and higher than carers of people with borderline personality disorder. Similarly, caseness for depression (69% of sample) or anxiety disorders (82%) in the sample was high. Relationship type, subtype expression (vulnerable/grandiose), and coping style were all found to significantly relate to experienced psychopathology. Although limitations exist regarding sample selection that may influence interpretation of results, these findings quantify the significant interpersonal impact of pathological narcissism in this sample.

Development and validation of an experience of time alone scale for borderline personality disorder.

BACKGROUND/OBJECTIVE: Intolerance of aloneness is considered a core feature of borderline personality disorder (BPD) that is clinically significant, yet under-researched. This study developed a measure of aloneness for individuals with BPD. METHOD: Interviews investigating the experience of aloneness for BPD participants (n = 12) formed the basis for the development of the measure. Pilot testing then occurred with BPD participants, control participants and qualified respondents. Validity, reliability and factor analysis of an Experience of Time Alone Scale (ETAS) was conducted with BPD participants (n = 112) and a comparison control group (n = 105). RESULTS: A three factor structure was revealed: (a) Cannot Cope Alone (α = .92), (b) Need to Escape from Others (α = .90), and (c) Consumed in Intolerable Distress (α = .88). The measure correlated significantly (p < .01) with the Mental Health Inventory, the Aloneness and Evocative Memory Scale, and the Hurvich Experience Inventory- Revised. Comparisons revealed highly significant differences between the BPD sample and control group on all subscales and the total score (U = 75.5, p = < .001, r = -.85). CONCLUSIONS: This study represents one of the first empirical examinations of a construct that has largely only been studied theoretically. This newly developed measure may contribute to diagnosis and therapy.

Clinician attitudes towards borderline personality disorder: A 15-year comparison.

Stigma towards people with borderline personality disorder has been a common theme reported within mental health services staff. A longitudinal, mixed method design investigated attitudes of mental health staff working at the same public health service in 2000 and 2015. Participants from both the 2000 and 2015 samples completed a short 10-item version of the Attitude to Personality Disorders Questionnaire and identical qualitative questions. The 2015 sample also completed the Attitude to Deliberate Self-Harm Questionnaire and the Attitude and Skills Questionnaire. Qualitatively, the 2000 sample endorsed much more negative descriptions (e.g. 'attention seeking' and 'manipulative'), and the 2015 sample focused more on treatment approaches and skills (e.g. 'management plan' and 'empathy'). Quantitatively, the 2015 sample endorsed more positive attitudes than the 2000 sample. This positive attitudinal shift is an encouraging step in successful treatment of borderline personality disorder and may reflect a changing landscape of the mental health system and greater awareness and use of effective treatments. © 2018 John Wiley & Sons, Ltd.

Cognitive-psychology expertise and the calculation of the probability of a wrongful conviction.

Cognitive psychologists are familiar with how their expertise in understanding human perception, memory, and decision-making is applicable to the justice system. They may be less familiar with how their expertise in statistical decision-making and their comfort working in noisy real-world environments is just as applicable. Here we show how this expertise in ideal-observer models may be leveraged to calculate the probability of guilt of Gary Leiterman, a man convicted of murder on the basis of DNA evidence. We show by common probability theory that Leiterman is likely a victim of a tragic contamination event rather than a murderer. Making any calculation of the probability of guilt necessarily relies on subjective assumptions. The conclusion about Leiterman's innocence is not overly sensitive to the assumptions-the probability of innocence remains high for a wide range of reasonable assumptions. We note that cognitive psychologists may be well suited to make these calculations because as working scientists they may be comfortable with the role a reasonable degree of subjectivity plays in analysis.

Intuitive Probabilities and the Limitation of Moral Imagination.

There is a vast literature that seeks to uncover features underlying moral judgment by eliciting reactions to hypothetical scenarios such as trolley problems. These thought experiments assume that participants accept the outcomes stipulated in the scenarios. Across seven studies (N = 968), we demonstrate that intuition overrides stipulated outcomes even when participants are explicitly told that an action will result in a particular outcome. Participants instead substitute their own estimates of the probability of outcomes for stipulated outcomes, and these probability estimates in turn influence moral judgments. Our findings demonstrate that intuitive likelihoods are one critical factor in moral judgment, one that is not suspended even in moral dilemmas that explicitly stipulate outcomes. Features thought to underlie moral reasoning, such as intention, may operate, in part, by affecting the intuitive likelihood of outcomes, and, problematically, moral differences between scenarios may be confounded with non-moral intuitive probabilities.

DNA Damage, Repair, and Cancer Metabolism.

Although there has been a renewed interest in the field of cancer metabolism in the last decade, the link between metabolism and DNA damage/DNA repair in cancer has yet to be appreciably explored. In this review, we examine the evidence connecting DNA damage and repair mechanisms with cell metabolism through three principal links. (1) Regulation of methyl- and acetyl-group donors through different metabolic pathways can impact DNA folding and remodeling, an essential part of accurate double strand break repair. (2) Glutamine, aspartate, and other nutrients are essential for de novo nucleotide synthesis, which dictates the availability of the nucleotide pool, and thereby influences DNA repair and replication. (3) Reactive oxygen species, which can increase oxidative DNA damage and hence the load of the DNA-repair machinery, are regulated through different metabolic pathways. Interestingly, while metabolism affects DNA repair, DNA damage can also induce metabolic rewiring. Activation of the DNA damage response (DDR) triggers an increase in nucleotide synthesis and anabolic glucose metabolism, while also reducing glutamine anaplerosis. Furthermore, mutations in genes involved in the DDR and DNA repair also lead to metabolic rewiring. Links between cancer metabolism and DNA damage/DNA repair are increasingly apparent, yielding opportunities to investigate the mechanistic basis behind potential metabolic vulnerabilities of a substantial fraction of tumors.

Isoflurane, a commonly used volatile anesthetic, enhances renal cancer growth and malignant potential via the hypoxia-inducible factor cellular signaling pathway in vitro.

BACKGROUND: Growing evidence indicates that perioperative factors, including choice of anesthetic, affect cancer recurrence after surgery although little is known about the effect of anesthetics on cancer cells themselves. Certain anesthetics are known to affect hypoxia cell signaling mechanisms in healthy cells by up-regulating hypoxia-inducible factors (HIFs). HIFs are also heavily implicated in tumorigenesis and high levels correlate with poor prognosis. METHODS: Renal cell carcinoma (RCC4) cells were exposed to isoflurane for 2 h at various concentrations (0.5-2%). HIF-1α, HIF-2α, phospho-Akt, and vascular endothelial growth factor A levels were measured by immunoblotting at various time points (0-24 h). Cell migration was measured across various components of extracellular matrix, and immunocytochemistry was used to analyze proliferation rate and cytoskeletal changes. RESULTS: Isoflurane up-regulated levels of HIF-1α and HIF-2α and intensified expression of vascular endothelial growth factor A. Exposed cultures contained significantly more cells (1.81 ± 0.25 vs. 1.00 of control; P = 0.03) and actively proliferating cells (89.4 ± 2.80 vs. 64.74 ± 7.09% of control; P = 0.016) than controls. These effects were abrogated when cells were pretreated with the Akt inhibitor, LY294002. Exposed cells also exhibited greater migration on tissue culture-coated (F = 16.89; P = 0.0008), collagen-coated (F = 20.99; P = 0.0003), and fibronectin-coated wells (F = 8.21; P = 0.011) as along with dramatic cytoskeletal rearrangement, with changes to both filamentous actin and α-tubulin. CONCLUSIONS: These results provide evidence that a frequently used anesthetic can exert a protumorigenic effect on a human cancer cell line. This may represent an important contributory factor to high recurrence rates observed after surgery.