Examining the shared and unique features of self-concept content and structure in Borderline Personality Disorder and Depression

AcceptedArticleCopyright © Springer Science+Business Media New York 2015The online version of this article (doi:10.1007/s10608-015-9695-3) contains supplementary material, which is available to authorized users.A number of clinical theories emphasise self-concept disturbance as central to borderline personality disorder (BPD). To date, however, there has been limited empirical examination of exactly how BPD changes the content and structure of self-concept. Moreover, it is unclear if patterns of self-concept disturbance are unique to BPD or are driven by axis-I comorbidities such as depression. To examine this issue, the present study adopted a dimensional design, examining how performance on a novel adaptation of a well-validated measure of self-concept (the Psychological Distance Scaling Task) was related to BPD and depression symptoms in a sample of 93 individuals with a wide range of symptom severity. While greater BPD severity was associated with less positive and more negative content of self-concept, this was driven by depression symptoms. Similarly, positive content was more diffuse and negative content more interconnected at higher levels of BPD severity, but for positive content, this was most clearly linked to comorbid depression features. In contrast, BPD severity (over and above depression symptoms) was uniquely associated with greater ‘clustering’ for positive and negative content (i.e. a more fragmented self-concept). This pattern of results lends support to clinical theories arguing that self-concept fragmentation is core to BPD and also supports the utility of dimensional analyses to identify patterns of cognitive-affective disturbance unique to BPD versus those shared with comorbid conditions like depression.MR

Beneficial effects of training in self-distancing and perspective broadening for people with a history of recurrent depression

This is the author accepted manuscript. The final version is available on open access from Elsevier via the DOI in this recordCognitive training designed to recalibrate maladaptive aspects of cognitiveaffective processing associated with the presence of emotional disorder can deliver clinical benefits. This study examined the ability of an integrated training in selfdistancing and perspective broadening (SD-PB) with respect to distressing experiences to deliver such benefits in individuals with a history of recurrent depression (>3 prior episodes), currently in remission. Relative to an overcoming avoidance (OA) control condition, SD-PB: a) reduced distress to upsetting memories and to newly encountered events, both during training when explicitly instructed to apply SD-PB techniques, and after-training in the absence of explicit instructions; b) enhanced capacity to self-distance from and broaden perspectives on participants’ experiences; c) reduced residual symptoms of depression. These data provide initial support for SD-PB as a low-intensity cognitive training providing a spectrum of cognitive and affective benefits for those with recurrent depression who are at elevated risk of future episodes.Medical Research Council (MRC

Culture and the remembering of trauma

This research investigated the influence of culture and posttraumatic stress disorder (PTSD) on global autobiographical remembering (Study 1a) and on the phenomenological properties (Study 1b) and memory-content variables (Study 1c) of trauma-specific autobiographical remembering. Australian, British, and Iranian trauma survivors with and without PTSD completed the Autobiographical Memory Test, Self-Defining Memory Task, and Autobiographical Memory Questionnaire and provided trauma- and negative-memory narratives. We found that there were pan-cultural deficits and distortions in the global autobiographical remembering of participants with PTSD (Study 1a). In addition, the presence of PTSD moderated the usual effect of culture on the phenomenological properties of the trauma memory (Study 1b). Finally, participants with PTSD, regardless of cultural background, had significantly fewer expressions of autonomy and self-determination in their autobiographical remembering than did those without PTSD (Study 1c). The findings suggest that pan-culturally, individuals with PTSD have similar disruptions and distortions in their autobiographical remembering

Ionised gas kinematics in bipolar H II regions

Stellar feedback plays a fundamental role in shaping the evolution of galaxies. Here we explore the use of ionised gas kinematics in young, bipolar H II regions as a probe of early feedback in these star-forming environments. We have undertaken a multiwavelength study of a young, bipolar H II region in the Galactic disc, G$316.81-0.06$, which lies at the centre of a massive ($\sim10^3$ M$_{\odot}$) infrared-dark cloud filament. It is still accreting molecular gas as well as driving a $\sim 0.2$ pc ionised gas outflow perpendicular to the filament. Intriguingly, we observe a large velocity gradient ($47.81 \pm 3.21$ km s$^{-1}$ pc$^{-1}$) across the ionised gas in a direction perpendicular to the outflow. This kinematic signature of the ionised gas shows a reasonable correspondence with the simulations of young H II regions. Based on a qualitative comparison between our observations and these simulations, we put forward a possible explanation for the velocity gradients observed in G$316.81-0.06$. If the velocity gradient perpendicular to the outflow is caused by rotation of the ionised gas, then we infer that this rotation is a direct result of the initial net angular momentum in the natal molecular cloud. If this explanation is correct, this kinematic signature should be common in other young (bipolar) H II regions. We suggest that further quantitative analysis of the ionised gas kinematics of young H II regions, combined with additional simulations, should improve our understanding of feedback at these early stages

Supernatants from lymphocytes stimulated with Bacillus Calmette-Guerin can modify the antigenicity of tumours and stimulate allogeneic T-cell responses

BACKGROUND: Reduced expression of class 1 human leucocyte antigens (HLA1) is often a mechanism by which tumours evade surveillance by the host immune system. This is often associated with an immune function that is unable to mount appropriate responses against disease, which can result in a state that favours carcinogenesis. METHODS: In the current study, we have explored the effects of Bacillus Calmette-Guerin (BCG) on the cytokine output of leucocytes, which is a key determinant in generating antitumour action, and have also assessed the effect of these cytokine cocktails on HLA1 expression in solid tumour cell lines. RESULTS: BCG potently activated a broad range of leucocytes, and also enhanced the production of cytokines that were Th(1)-predominant. Supernatants from BCG-treated leucocytes significantly increased the expression of HLA1 on the surface of cancer cell lines, which correlated with increased cytolytic T-cell activity. We also showed that the increased HLA1 expression was associated with activation of intracellular signalling pathways, which was triggered by the increases in the Th(1)-cytokines interferon-γ and tumour necrosis factor-α, as counteracting their effects negated the enhancement. CONCLUSION: These studies reaffirm the role of BCG as a putative immunotherapy through their cytokine-modifying effects on leucocytes and their capacity to enhance tumour visibility

Mitigating Coronavirus Induced Dysfunctional Immunity for At-Risk Populations in COVID-19: Trained Immunity, BCG and "New Old Friends".

The novel, highly contagious coronavirus SARS-CoV-2 spreads rapidly throughout the world, leading to a deadly pandemic of a predominantly respiratory illness called COVID-19. Safe and effective anti-SARS-CoV-2 vaccines are urgently needed. However, emerging immunological observations show hallmarks of significant immunopathological characteristics and dysfunctional immune responses in patients with COVID-19. Combined with existing knowledge about immune responses to other closely related and highly pathogenic coronaviruses, this could forebode significant challenges for vaccine development, including the risk of vaccine failure. Animal data from earlier coronavirus vaccine efforts indicate that elderly people, most at risk from severe COVID-19 disease, could be especially at risk from immunopathologic responses to novel coronavirus vaccines. Bacterial "new old friends" such as Bacille Calmette-Guérin (BCG) or Mycobacterium obuense have the ability to elevate basal systemic levels of type 1 cytokines and immune cells, correlating with increased protection against diverse and unrelated infectious agents, called "trained immunity." Here we describe dysfunctional immune responses induced by coronaviruses, representing potentially difficult to overcome obstacles to safe, effective vaccine development for COVID-19, and outline how trained immunity could help protect high risk populations through immunomodulation with BCG and other "new old friends.

Modulation of the virus-receptor interaction by mutations in the V5 loop of feline immunodeficiency virus (FIV) following in vivo escape from neutralising antibody

<b>BACKGROUND:</b> In the acute phase of infection with feline immunodeficiency virus (FIV), the virus targets activated CD4+ T cells by utilising CD134 (OX40) as a primary attachment receptor and CXCR4 as a co-receptor. The nature of the virus-receptor interaction varies between isolates; strains such as GL8 and CPGammer recognise a "complex" determinant on CD134 formed by cysteine-rich domains (CRDs) 1 and 2 of the molecule while strains such as PPR and B2542 require a more "simple" determinant comprising CRD1 only for infection. These differences in receptor recognition manifest as variations in sensitivity to receptor antagonists. In this study, we ask whether the nature of the virus-receptor interaction evolves in vivo.<p></p> <b>RESULTS:</b> Following infection with a homogeneous viral population derived from a pathogenic molecular clone, a quasispecies emerged comprising variants with distinct sensitivities to neutralising antibody and displaying evidence of conversion from a "complex" to a "simple" interaction with CD134. Escape from neutralising antibody was mediated primarily by length and sequence polymorphisms in the V5 region of Env, and these alterations in V5 modulated the virus-receptor interaction as indicated by altered sensitivities to antagonism by both anti-CD134 antibody and soluble CD134.<p></p> <b>CONCLUSIONS:</b> The FIV-receptor interaction evolves under the selective pressure of the host humoral immune response, and the V5 loop contributes to the virus-receptor interaction. Our data are consistent with a model whereby viruses with distinct biological properties are present in early versus late infection and with a shift from a "complex" to a "simple" interaction with CD134 with time post-infection.<p></p&gt

Preserved cognitive functions with age are determined by domain-dependent shifts in network responsivity

Healthy ageing has disparate effects on different cognitive domains. The neural basis of these differences, however, is largely unknown. We investigated this question by using Independent Components Analysis to obtain functional brain components from 98 healthy participants aged 23-87 years from the population-based Cam-CAN cohort. Participants performed two cognitive tasks that show age-related decrease (fluid intelligence and object naming) and a syntactic comprehension task that shows age-related preservation. We report that activation of task-positive neural components predicts inter-individual differences in performance in each task across the adult lifespan. Furthermore, only the two tasks that show performance declines with age show age-related decreases in task-positive activation of neural components and decreasing default mode (DM) suppression. Our results suggest that distributed, multi-component brain responsivity supports cognition across the adult lifespan, and the maintenance of this, along with maintained DM deactivation, characterizes successful ageing and may explain differential ageing trajectories across cognitive domains

The posttraumatic stress disorder diagnosis in preschool- and elementary school-age children exposed to motor vehicle accidents

Objective: Increasingly, children are being diagnosed with psychiatric disorders, including preschool-age children. These diagnoses in young children raise questions pertaining to 1) how diagnostic algorithms for individual disorders should be modified for young age groups, 2) how psychopathology is best detected at an early stage, and 3) how to make use of multiple informants. The authors examined these issues in a prospective longitudinal assessment of preschool- and elementary school-age children who were exposed to a traumatic event. Method: Participants were 114 children (age range: 2-10 years) who had experienced a motor vehicle accident. Parents and older children (age range: 7-10 years) completed structured interviews 2-4 weeks (initial assessment) and 6 months (6-month follow-up) after the traumatic event. A recently proposed alternative symptom algorithm for diagnosing posttraumatic stress disorder (PTSD) was utilized and compared with the standard DSM-IV algorithms for diagnosing PTSD and acute stress disorder. Results: At the 2- to 4-week assessment, 11.5% of the children met conditions for a diagnosis of PTSD based on the alternative algorithm criteria per parent report, and 13.9% met criteria for this diagnosis at the 6-month follow-up. These percentages were much higher than those for DSM-IV diagnoses of acute stress disorder and PTSD. Among 7- to 10-year-old subjects, the use of combined parent- and child-reported symptoms to derive a diagnosis resulted in an increased number of children in this age group who were identified with psychiatric illness relative to the use of parent report alone. Agreement between parent and child on symptoms for 1) a diagnosis of PTSD based on the alternative algorithm criteria and 2) diagnoses of DSM-IV acute stress disorder and PTSD in this age group was poor. Among 2- to 6-year-old subjects, the alternative algorithm PTSD diagnosis per parent report was a more sensitive predictor of later onset psychopathology relative to a diagnosis of DSM-IV acute stress disorder or PTSD per parent report. However, among 7- to 10-year-old subjects, a combined symptom report (from both parent and child) was optimal in predicting posttraumatic psychopathology. Conclusions: These findings support the use of the proposed alternative algorithm for assessing PTSD in young children and suggest that the diagnosis of PTSD based on the alternative algorithm criteria is stable from the acute phase onward. When both parent- and child-reported symptoms are utilized for the assessment of PTSD among 7- to 10-year-old children, the alternative algorithm and DSM-IV criteria have broad comparable validity. However, in the absence of child-reported symptoms, the alternative algorithm criteria per parent report appears to be an optimal diagnostic measure of PTSD among children in this age group, relative to the standard DSM-IV algorithm for diagnosing the disorder

Multiple determinants of lifespan memory differences

Memory problems are among the most common complaints as people grow older. Using structural equation modeling of commensurate scores of anterograde memory from a large (N = 315), population-derived sample (www.cam-can.org), we provide evidence for three memory factors that are supported by distinct brain regions and show differential sensitivity to age. Associative memory and item memory are dramatically affected by age, even after adjusting for education level and fluid intelligence, whereas visual priming is not. Associative memory and item memory are differentially affected by emotional valence, and the age-related decline in associative memory is faster for negative than for positive or neutral stimuli. Gray-matter volume in the hippocampus, parahippocampus and fusiform cortex, and a white-matter index for the fornix, uncinate fasciculus and inferior longitudinal fasciculus, show differential contributions to the three memory factors. Together, these data demonstrate the extent to which differential ageing of the brain leads to differential patterns of memory loss