Memory function in borderline personality disorder

Borderline Personality Disorder (BPD) is a severe psychiatric condition that involves impairment in multiple areas of psychological functioning including disturbed cognition, impulsivity, and intense unstable relationships. Memory deficits are not recognised as a core symptom of BPD, but BPD patients have long been suspected of having inaccurate perceptions, disturbed memory processes, and an increased tendency to generate false memories about past events, interpersonal perceptions, and social interactions. The overarching goal of my PhD was to investigate potential memory differences in people with features of BPD. In particular, I examined whether people with more BPD symptoms would be more susceptible to false memories or would exhibit irregularities in autobiographical memory. In addition, I also compared the traditional conceptualisation of BPD with the alternative model of personality disorders in predicting memory performance. A total of 300 university students were recruited to participate in the main experiment. Participants were asked to complete a series of psychological assessments that measured various aspects of personality and psychopathology. In addition, each participant took part in a false memory procedure, the Deese/Roediger-McDermott (DRM) paradigm, using word lists that were developed in the course of preliminary research (Chapter 4). Participants were also asked to report about both their earliest personal memory and a memory that reflected an important turning point in their lives (see Chapter 5 for the complete Method). I then examined how BPD features are associated with false memory (Chapter 6) and how dissociation is associated with false memory (Chapter 7). In the final two empirical chapters, I investigated how BPD features are related to the qualities of autobiographical narratives (Chapter 8) and how borderline symptoms are reflected in the nature of narrative identity (Chapter 9). Overall, I found that 1) using the BPD traditional model, BPD symptoms were correlated with higher false memory for positive information, and in the alternative model of BPD, identity impairment and anxiousness were correlated with the overall false memory score; 2) irrespective of BPD, experiencing trauma and dissociation, as well as lower levels of intelligence, were associated with higher false memory; 3) trauma and dissociation mediated the relation between BPD and false memory; 4) both the traditional and alternative models of BPD were correlated with negative affect in turning-point memories, but not in earliest memories; 5) relying on the traditional model of BPD, I found no correlation between over-general memories and BPD, however, using the alternative model, over-general turning-point memories were associated with higher BPD-related impairment in self-direction; 6) participants with features of BPD were more likely to rate their earliest memories as more negative in valence and less coherent; 7) participants with features of BPD were more likely to rate their turning-point memories as negative in valence, to describe them from a 3rd-person perspective, and to reflect higher distancing, greater emotional intensity, and less accessibility; 8) participants with higher features of BPD also reported turning point memories that were also less likely to reflect their sense of agency, agency fulfilment, intimacy and empathy; and 9) narrative identity, but not narrative intimacy and coherence, was the dominant predictor of BPD features. Overall, I also found that both the traditional and alternative models of BPD predict the expected qualities of memory, with the alternative model of BPD doing better in determining which diagnostic subtypes of BPD predict the trajectories of false memory. Taken together, the current findings not only have important theoretical implications for understanding memory differences in BPD, but they also have practical implications in clinical settings

Memory function in borderline personality disorder

Borderline Personality Disorder (BPD) is a severe psychiatric condition that involves impairment in multiple areas of psychological functioning including disturbed cognition, impulsivity, and intense unstable relationships. Memory deficits are not recognised as a core symptom of BPD, but BPD patients have long been suspected of having inaccurate perceptions, disturbed memory processes, and an increased tendency to generate false memories about past events, interpersonal perceptions, and social interactions. The overarching goal of my PhD was to investigate potential memory differences in people with features of BPD. In particular, I examined whether people with more BPD symptoms would be more susceptible to false memories or would exhibit irregularities in autobiographical memory. In addition, I also compared the traditional conceptualisation of BPD with the alternative model of personality disorders in predicting memory performance. A total of 300 university students were recruited to participate in the main experiment. Participants were asked to complete a series of psychological assessments that measured various aspects of personality and psychopathology. In addition, each participant took part in a false memory procedure, the Deese/Roediger-McDermott (DRM) paradigm, using word lists that were developed in the course of preliminary research (Chapter 4). Participants were also asked to report about both their earliest personal memory and a memory that reflected an important turning point in their lives (see Chapter 5 for the complete Method). I then examined how BPD features are associated with false memory (Chapter 6) and how dissociation is associated with false memory (Chapter 7). In the final two empirical chapters, I investigated how BPD features are related to the qualities of autobiographical narratives (Chapter 8) and how borderline symptoms are reflected in the nature of narrative identity (Chapter 9). Overall, I found that 1) using the BPD traditional model, BPD symptoms were correlated with higher false memory for positive information, and in the alternative model of BPD, identity impairment and anxiousness were correlated with the overall false memory score; 2) irrespective of BPD, experiencing trauma and dissociation, as well as lower levels of intelligence, were associated with higher false memory; 3) trauma and dissociation mediated the relation between BPD and false memory; 4) both the traditional and alternative models of BPD were correlated with negative affect in turning-point memories, but not in earliest memories; 5) relying on the traditional model of BPD, I found no correlation between over-general memories and BPD, however, using the alternative model, over-general turning-point memories were associated with higher BPD-related impairment in self-direction; 6) participants with features of BPD were more likely to rate their earliest memories as more negative in valence and less coherent; 7) participants with features of BPD were more likely to rate their turning-point memories as negative in valence, to describe them from a 3rd-person perspective, and to reflect higher distancing, greater emotional intensity, and less accessibility; 8) participants with higher features of BPD also reported turning point memories that were also less likely to reflect their sense of agency, agency fulfilment, intimacy and empathy; and 9) narrative identity, but not narrative intimacy and coherence, was the dominant predictor of BPD features. Overall, I also found that both the traditional and alternative models of BPD predict the expected qualities of memory, with the alternative model of BPD doing better in determining which diagnostic subtypes of BPD predict the trajectories of false memory. Taken together, the current findings not only have important theoretical implications for understanding memory differences in BPD, but they also have practical implications in clinical settings

Comprehensive integrated single-cell RNA sequencing analysis of brain metastasis and glioma microenvironment: Contrasting heterogeneity landscapes.

Understanding the specific type of brain malignancy, source of brain metastasis, and underlying transformation mechanisms can help provide better treatment and less harm to patients. The tumor microenvironment plays a fundamental role in cancer progression and affects both primary and metastatic cancers. The use of single-cell RNA sequencing to gain insights into the heterogeneity profiles in the microenvironment of brain malignancies is useful for guiding treatment decisions. To comprehensively investigate the heterogeneity in gliomas and brain metastasis originating from different sources (lung and breast), we integrated data from three groups of single-cell RNA-sequencing datasets obtained from GEO. We gathered and processed single-cell RNA sequencing data from 90,168 cells obtained from 17 patients. We then employed the R package Seurat for dataset integration. Next, we clustered the data within the UMAP space and acquired differentially expressed genes for cell categorization. Our results underscore the significance of macrophages as abundant and pivotal constituents of gliomas. In contrast, lung-to-brain metastases exhibit elevated numbers of AT2, cytotoxic CD4+ T, and exhausted CD8+ T cells. Conversely, breast-to-brain metastases are characterized by an abundance of epithelial and myCAF cells. Our study not only illuminates the variation in the TME between brain metastasis with different origins but also opens the door to utilizing established markers for these cell types to differentiate primary brain metastatic cancers

Unveiling the Future of Cancer Treatment: A Cutting‐Edge Review on the Role of Nanotherapeutics in Targeting Long Non‐Coding RNAs

International audienceThis review article spotlights the burgeoning potential of using nanotherapeutic strategies to target long non‐coding RNAs (lncRNAs) in cancer cells. This updated discourse underlines the prominent role of lncRNAs in instigating cancer, facilitating its progression, and metastasis, validating lncRNAs' potential for being effective diagnostic biomarkers and therapeutic targets. The manuscript offers an in‐depth examination of different strategies presently employed to modulate lncRNA expression and function for therapeutic purposes. Among these strategies, Antisense Oligonucleotides (ASOs), RNA interference (RNAi) technologies, and the innovative CRISPR‐based gene editing tools garner noteworthy mention. A significant section of the review is dedicated to nanocarriers and their crucial role in drug delivery. These nanocarriers' efficiency in targeting lncRNAs in varied types of cancers is elaborated upon, validating the importance of targeted therapy. The manuscript culminates by reaffirming the promising prospects of targeting lncRNAs to enhance the accuracy of cancer diagnosis and improve treatment efficacy. Consequently, new paths are opened to more research and innovation in employing nanotherapeutic approaches against lncRNAs in cancer cells. Thus, this comprehensive manuscript serves as a valuable resource that underscores the vital role of lncRNAs and the various nano‐strategies for targeting them in cancer treatment

Cancer chemotherapy resistance: Mechanisms and recent breakthrough in targeted drug delivery

Conventional chemotherapy, one of the most widely used cancer treatment methods, has serious side effects, and usually results in cancer treatment failure. Drug resistance is one of the primary reasons for this failure. The most significant drawbacks of systemic chemotherapy are rapid clearance from the circulation, the drug's low concentration in the tumor site, and considerable adverse effects outside the tumor. Several ways have been developed to boost neoplasm treatment efficacy and overcome medication resistance. In recent years, targeted drug delivery has become an essential therapeutic application. As more mechanisms of tumor treatment resistance are discovered, nanoparticles (NPs) are designed to target these pathways. Therefore, understanding the limitations and challenges of this technology is critical for nanocarrier evaluation. Nano-drugs have been increasingly employed in medicine, incorporating therapeutic applications for more precise and effective tumor diagnosis, therapy, and targeting. Many benefits of NP-based drug delivery systems in cancer treatment have been proven, including good pharmacokinetics, tumor cell-specific targeting, decreased side effects, and lessened drug resistance. As more mechanisms of tumor treatment resistance are discovered, NPs are designed to target these pathways. At the moment, this innovative technology has the potential to bring fresh insights into cancer therapy. Therefore, understanding the limitations and challenges of this technology is critical for nanocarrier evaluation.Ministerio de Ciencia e Innovación (MICIN)Agencia Estatal de InvestigaciónUnión EuropeaUniversidad Complutense de MadridDepto. de Bioquímica y Biología MolecularFac. de Ciencias BiológicasTRUEpu