[Borderline personality disorder: state of knowledge and attitudes among french-speaking mental health professionnals]. / Trouble de la personnalité borderline: état des connaissances et des représentations auprès de praticiens francophones en santé mentale.

OBJECTIVES: Patients suffering from borderline personality disorder are very prevalent in various settings (emergency rooms, psychiatric and general hospitals, ambulatory consultations). However, it remains one of the most stigmatized and neglected mental health conditions, albeit being an area that is responsible for very interesting advances in psychotherapy. Today, the prognosis of patients with borderline personality disorder is rather favorable, provided that they follow a dedicated psychotherapy. Conceptions about this condition therefore deserve to be updated as it is sufficiently described in the literature that negative attitudes towards these patients diminish the quality of care they receive as well as their prognosis, and that these attitudes change with training. We decided to study the state of knowledge and attitudes towards borderline personality disorder in a group of French-speaking caregivers interested in these patients. METHODS: Between 2019 and 2020, at the start of training sessions in psychotherapeutic approaches to borderline personality disorder, we provided two questionnaires to 126 caregivers from various professional backgrounds (psychiatrists or child psychiatrists, psychologists, mental health nurses, social workers). The first consisted of 13 questions with 3 choice answers aimed at testing knowledge about borderline personality disorder and the second of 11 questions in the form of a Likert scale aimed at evaluating attitudes towards these patients (e.g. degree of comfort, involvement, hope, avoidance with these patients) adapted frome a questionnaire of Blake and colleagues. RESULTS: The sample consisted of 126 caregivers (69 psychiatrists/pedopsychiatrists; 19 mental health nurses; 23 psychologists; 14 social workers). Fifty three of them (42.06 %) worked in an outpatient setting (either in a state facility or in private practice), 50 (39.68 %) worked in an inpatient psychiatric unit, 13 (10.32%) in both care systems, and 10 (7.94 %) worked in other facilities such as sheltered homes or workshops for persons with psychiatric disabilities. The average number of years in postgraduate training was 7.73 (SD=5.67; rank=0 to 31), and 35 (27.78%) had received at least one training course on borderline disorder in the past. The mean age of the sample was 37.89 (SD=10.08; rank=20 to 64) and there were 76 women (60.32%) and 50 men (39.68%). Concerning the first questionnaire (knowledge), the rate of correct responses among caregivers was relatively low (54%) considering that the vast majority of those assessed were caregivers already trained in mental health who were working with patients suffering from borderline personality disorder. The results showed a significant knowledge gap among professionals, in particular in the nursing profession, illustrating an ever more flagrant shortfall in formations in this sub-population. Concerning the second questionnaire (attitudes), the answers showed that attitudes of caregivers towards patients with borderline personality disorder were still tinged with fear and lack of confidence in taking charge of them. Thus, one participant out of five would have liked to avoid these patients, more than 12% of caregivers did not appreciate them, and 23% thought that they were manipulative. In addition, nearly half of the caregivers surveyed had low confidence in their ability to make a positive difference in the lives of borderline patients. However, there was a recognition of their distress as well as a demand for dedicated training. CONCLUSIONS: Stigmas and ignorance persist around patients with borderline personality disorder. Current training courses do not allow caregivers who are on the front lines (in particular nurses) and who wish to be trained to acquire sufficient knowledge and tools necessary for the care of patients suffering from this disorder. This calls for an improvement in training as well as a reflection on the most appropriate approaches possible to the various target audiences.

Emergency psychiatric management of borderline personality disorder: Towards an articulation of modalities for personalised integrative care.

Building on existing literature, the authors draw the landscape of psychiatric emergencies, and focus on borderline personality disorder, frequently encountered, and strongly linked to death by suicide. A review of knowledge in terms of diagnosis, prognosis, etiology, and treatment, as well as their own experiences, lead them to propose areas of progress that would secure the patient's care pathway. The evolution of society has led psychiatric emergency departments to play the role of a safety net and an entry point to the mental health system. Borderline personality disorder is one of the most common pathologies encountered in psychiatric emergencies. It represents a major concern, long characterized by an often dramatic evolution, and by the human and economic stress it generates. However, since the 1990s, knowledge of this disorder has been refined, and today there are various means of evaluation, good clinical practices and psychotherapeutic treatments, thanks to which significant and lasting improvement is possible. Recent studies highlight the crucial role of hospital caregivers, and the benefit of consolidating their skills by providing them with the knowledge and tools specific to this disorder. They also converge on the interest of setting up specific emergency treatment modalities, particularly highly structured, safe and empowering for the patient, in order to improve their effectiveness. The authors suggest that a case formulation model for persons with borderline personality disorder in emergency would make it possible to activate these two levers of progress, while improving collaboration between hospital and outpatient care. This would also address their main concern of optimizing the patient's therapeutic pathway and reinforcing adherence to treatment that could bring remission, and should be supported by data from empirical research.

[Mentalization based treatment (MBT) for borderline personality disorder among a population of French-speaking patients]. / Implémentation francophone de la thérapie basée sur la mentalisation (TBM) pour le trouble de personnalité limite.

INTRODUCTION: Borderline Personality Disorder is a frequent disorder that is challenging for therapists to treat due to the prevalence of self-damaging and suicidal behaviours and interruptions of the therapeutic alliance, as well as a poor response to psychotropic treatments. In recent years, several empirically-validated psychotherapeutic treatments have been developed, including Mentalisation-Based Therapy, which is an integrative psychodynamic approach created in Britain. Although numerous studies have showed Mentalisation-Based Therapy to be an efficient treatment of Borderline Personality Disorder, its specific components have yet to be assessed. Furthermore, there have been no empirical studies conducted among groups of French-speaking patients. The purpose of this study is twofold: To provide an initial assessment of the efficacy of the mentalisation-based psycho-educational component, which is the first component of any mentalisation-based therapy, and to provide the first assessment of this approach among a population of French-speaking patients. METHOD: Over a three-month period, 14 Borderline Personality Disorder sufferers followed a psycho-educational Mentalisation-Based Therapy programme consisting of group sessions to introduce patients to mentalisation and weekly individual interviews. Patients filled in various question forms assessing, among others, the intensity of their depression, their degree of hopelessness, their emotional regulation strategies, and their reflective abilities. RESULTS: The psycho-educational component of Mentalisation-Based Therapy is significantly associated with improved cognitive emotional regulation, empathy and reflective abilities, and with a reduced sense of hopelessness. The programme retention rate was of 71.4%. CONCLUSION: Despite the small sample size and the short treatment period, these preliminary results demonstrate the efficiency of the psycho-educational phase of Mentalisation-Based Therapy, and in particular the positive effects of the treatment on depressive symptomatology and self-regulation processes among patients with a Borderline Personality Disorder diagnosis.

Retraction Note to: L-glutamine supplementation induces insulin resistance in adipose tissue and improves insulin signalling in liver and muscle of rats with diet-induced obesity.

In light of forensic evidence indicating duplication and/or manipulation of western blot images the Editor-in-Chief is retracting the article cited above.

Linking Gut Microbiota and Inflammation to Obesity and Insulin Resistance.

Obesity and insulin resistance are the major predisposing factors to comorbidities, such as Type 2 diabetes, nonalcoholic fatty liver disease, cardiovascular and neurodegenerative diseases, and several types of cancer. The prevalence of obesity is still increasing worldwide and now affects a large number of individuals. Here, we review the role of the gut microbiota in the pathophysiology of insulin resistance/obesity. The human intestine is colonized by ∼100 trillion bacteria, which constitute the gut microbiota. Studies have shown that lean and overweight rodents and humans may present differences in the composition of their intestinal flora. Over the past 10 years, data from different sources have established a causal link between the intestinal microbiota and obesity/insulin resistance. It is important to emphasize that diet-induced obesity promotes insulin resistance by mechanisms independent and dependent on gut microbiota. In this review, we present several mechanisms that contribute to explaining the link between intestinal flora and insulin resistance/obesity. The LPS from intestinal flora bacteria can induce a chronic subclinical inflammatory process and obesity, leading to insulin resistance through activation of TLR4. The reduction in circulating SCFA may also have an essential role in the installation of reduced insulin sensitivity and obesity. Other mechanisms include effects of bile acids, branched-chain amino acids (BCAA), and some other lesser-known factors. In the near future, this area should open new therapeutic avenues for obesity/insulin resistance and its comorbidities.

Cdc2-like kinase 2 in the hypothalamus is necessary to maintain energy homeostasis.

OBJECTIVE: To investigate whether the Cdc2-like kinase 2 (CLK2) is expressed in hypothalamic neurons and if it is, whether the hypothalamic CLK2 has a role in the regulation of energy balance. SUBJECTS: Swiss mice on chow or high-fat diet (HFD) and db/db mice on chow diet were used to address the role of CLK2 in the hypothalamus. RESULTS: Hypothalamic CLK2Thr343 phosphorylation, which induces CLK2 activity, is regulated in vivo by refeeding, insulin and leptin, in a PI3K (phosphoinositide 3-kinase)-dependent manner. The reduction of CLK2 expression in the hypothalamus, by chronic pharmacological inhibition with TG003 or by chronic knockdown with small interfering RNA was sufficient to abolish the anorexigenic effect of insulin and leptin, to increase body weight, fat mass, food intake and to decrease energy expenditure in mice on chow. In contrast, CLK2Thr343 phosphorylation in the hypothalamus in response to insulin, leptin or refeeding was impaired in mice on HFD or in db/db mice. Chronic CLK2 inhibition in the hypothalamus was associated with a slight increase in the fasting blood glucose levels, reduction in PEPCK (phosphoenolpyruvate carboxykinase) expression in the liver and enhanced glucose production from pyruvate, suggesting a regulation of hepatic glucose production. Further, overexpressing CLK2 in the mediobasal hypothalami of mice on HFD or in db/db mice by adenovirus partially reversed the obese phenotype. CONCLUSIONS: Thus, our results suggest that protein CLK2 integrates some important hypothalamic pathways, and may be a promising molecule for new therapeutic approaches for obesity and diabetes.

Pioglitazone treatment increases food intake and decreases energy expenditure partially via hypothalamic adiponectin/adipoR1/AMPK pathway.

INTRODUCTION: Thiazolidinediones (TZDs) enhanced body weight (BW) partially by increased adipogenesis and hyperphagia. Neuronal PPARγ knockout mice on high-fat diet (HFD) are leaner because of enhanced leptin response, although it could be secondary to their leanness. Thus, it still is an open question how TZDs may alter energy balance. Multiple factors regulate food intake (FI) and energy expenditure (EE), including anorexigenic hormones as insulin and leptin. Nonetheless, elevated hypothalamic AMPK activity increases FI and TZDs increase AMPK activity in muscle cells. Thus, the aim of the present study was to investigate whether Pioglitazone (PIO) treatment alters hypothalamic insulin and leptin action/signaling, AMPK phosphorylation, and whether these alterations may be implicated in the regulation of FI and EE. METHODS: Swiss mice on HFD (2 months) received PIO (25 mg kg(-1) per day-gavage) or vehicle for 14 days. AMPK and AdipoR1 were inhibited via Intracerebroventricular injections using Compound C (CompC) and small interference RNA (siRNA), respectively. Western blot, real-time PCR and CLAMS were done. RESULTS: PIO treatment increased BW, adiposity, FI, NPY mRNA and decreased POMC mRNA expression and EE in HFD mice. Despite higher adiposity, PIO treatment improved insulin sensitivity, glucose tolerance, decreased insulin and increased adiponectin serum levels. This result was associated with, improved insulin and leptin action/signaling, decreased α2AMPK(Ser491) phosphorylation and elevated Acetyl-CoA carboxylase and AMPK(Thr172) phosphorylation in hypothalamus. The inhibition of hypothalamic AMPK with CompC was associated with decreased adiposity, FI, NPY mRNA and EE in PIO-treated mice. The reduced expression of hypothalamic AdipoR1 with siRNA concomitantly with PIO treatment reverted PIO induced obesity development, suggesting that adiponectin may be involved in this effect. CONCLUSIONS: These results demonstrated that PIO, despite improving insulin/leptin action in hypothalamus, increases FI and decreases EE, partially, by activating hypothalamic adiponectin/AdipoR1/AMPK axis. Suggesting a novel mechanism in the hypothalamus by which TZDs increase BW.

[Current therapies of borderline personality disorder]. / Thérapies actuelles du trouble de personnalité borderline.

Borderline personality disorder (BPD) is a highly prevalent disorder characterized by identity disturbance, emotion dysregulation, interpersonal difficulties and self-damaging behaviours. Mental health professionals most of the time encounter difficulties in the care of these hard-to-treat patients mainly due to the frequent crises often leading to drop-outs. In this perspective, technical and theoretical changes to traditional psychotherapeutic approaches were developed. We here give the major principles that should be considered when treating BPD patients in order not only to reduce the risk of being iatrogenic but also to apply the current psychotherapeutic and psychiatric modalities internationally recognized to be efficient.

Late vascular complications after cranial radiotherapy: A report of two illustrative cases.

Cranial radiotherapy (CRT) is used to treat a large variety of benign and malignant disorders. We present two cases of late neurological complications after CRT and briefly discuss its diagnosis and their shared pathophysiological aspects. The first case is a patient with cognitive impairment associated to mineralizing microangiopathy ten years after CRT for nasopharyngeal carcinoma and the second one is a woman with Stroke-like Migraine Attacks after Radiation Therapy (SMART) syndrome two years after CRT for anaplastic meningioma. Nowadays, higher survival rates might cause an increase in appearance of late neurological complications after CTR. These reported cases show that late complications can mimic a wide variety of neurological conditions and the importance of magnetic resonance image (MRI) to get a diagnosis.

[A combined medical-psychiatric unit for the management of complex cases]. / L'UPHA, une unité médico-psychiatrique pour la prise en charge des cas complexes.

The management of patients with coexisting medical and psychiatric disorders constitutes a serious challenge for the hospital team in charge of their care. Medical teams working in traditional hospital settings often find themselves ill-equipped when faced with the complex care needs of such patients. This article describes a unit at the University Hospital of Geneva specifically designed to manage the care of patients with combined medical and psychiatric disorders. It discusses the comprehensive management of such patients using clinical vignettes.

High-dose-rate intensity modulated brachytherapy with external-beam radiotherapy improves local and biochemical control in patients with high-risk prostate cancer.

Purpose Our aim was to report the 8-year outcome of local dose escalation using high-dose-rate conformal brachytherapy combined with external irradiation for patients with high-risk prostate cancer. Material and methods From June 1998 to June 2007, 134 patients with high-risk localized prostate cancer were prospectively enrolled in the study. The median follow-up was 45 months (12-107). Only patients considered as having high-risk criteria were accepted [prostate-specific antigen (PSA) > or =20 ng/ml and/or Gleason >7 and/or stage > or =T3a or two intermediate-risk criteria: PSA 11-19 ng/ml, Gleason 7, stage T2b-c]. The total dose applied by external beam radiotherapy was 46 Gy in 200-cGy daily fractions. High-dose-rate brachytherapy was performed at the end of weeks 1 and 3 of the 5-week radiotherapy course. The doses administered in each application was 1,150 cGy. Any patient free of clinical or biochemical evidence of disease was termed b-NED. Actuarial rates of outcome were calculated by Kaplan. Meier analysis and compared using the log-rank test. Cox regression models were used to establish prognostic factors of the measures of outcome. Results Mean follow-up for the entire group was 45 months (range 12-107). The overall survival (OS) according to Kaplan-Meier estimates was 85% (+/-5) at 5 and 8 years. The 5 and 8 years for biochemical control were 80% (+/-4%) and 73% (+/-7%), respectively, whereas for failure in tumor-free survival (TFS), they were 82% (+/-3) at 5 and 8 years, respectively. The 8-year cause-specific mortality was 10% (+/-4%). The multivariate Cox regression analyses identified the number of poor prognostic factors as independent for biochemical failure. Our report includes only patients considered as high risk, and the 8-year b-NED survival rate was 83% for patients with two intermediate-risk criteria, 78% for patients with one poor prognostic factor, 56% for two and 35% for all three (p = 0.001). There were no urethral strictures and/or urinary incontinence. Gastrointestinal toxicity grade 2 was 7.5%. Conclusions The 8-year results confirm the feasibility and effectiveness of external-beam radiation therapy with conformal high-dose-rate brachytherapy boost for patients with high-risk tumor. The late toxicity rates were low, corroborating the excellent dose conformity.

[Brachyterapy in localized prostate cancer]. / Braquiterapia en el cáncer de próstata localizado.

INTRODUCTION AND OBJECTIVES: Considering the high frequency of localized prostate cancer in stages, at the moment there are minimally invasive techniques that compete with the classic surgery. One of them is the Low Dose Rate (LDR) Brachytherapy with permanent implants of 1125 seeds. The objective of the present study is to expose our experience from the year 1998, when we made the first treatment, until today. The results and the morbidity of the patients over a 7 and a half years period are analyzed. MATERIAL AND METHODS: A total of 800 patients were treated with LDR brachytherapy, with average age of 68 years and range between 48 and 83 years. In all patients the 1125 seeds were used with Rapid-Strand and peripheral load by means of intraoperative planning. RESULTS: The urinary rate of complications was of 3% of AUR, and 0.2% of urinary incontinence. The morbidity on the digestive apparatus was of a 12% intermittent bleeding, 2% of proctitis, and a 0.3% of rectal fistulas.

Homogeneous assays based on deoxyribozyme catalysis.

We report herein the first homogeneous assays based on the ribonuclease activity of a deoxyribozyme. The previously reported deoxyribozyme was covalently modified with biotin and used to assay biotin-binding interactions through changes in fluorescence upon substrate turnover. Deoxyribozymes with fluorescence-based reporting have the potential to serve as general analytical tools.

Borderline personality disorder and childhood maltreatment: a genome-wide methylation analysis.

Early life adversity plays a critical role in the emergence of borderline personality disorder (BPD) and this could occur through epigenetic programming. In this perspective, we aimed to determine whether childhood maltreatment could durably modify epigenetic processes by the means of a whole-genome methylation scan of BPD subjects. Using the Illumina Infinium® HumanMethylation450 BeadChip, global methylation status of DNA extracted from peripheral blood leucocytes was correlated to the severity of childhood maltreatment in 96 BPD subjects suffering from a high level of child adversity and 93 subjects suffering from major depressive disorder (MDD) and reporting a low rate of child maltreatment. Several CpGs within or near the following genes (IL17RA, miR124-3, KCNQ2, EFNB1, OCA2, MFAP2, RPH3AL, WDR60, CST9L, EP400, A2ML1, NT5DC2, FAM163A and SPSB2) were found to be differently methylated, either in BPD compared with MDD or in relation to the severity of childhood maltreatment. A highly relevant biological result was observed for cg04927004 close to miR124-3 that was significantly associated with BPD and severity of childhood maltreatment. miR124-3 codes for a microRNA (miRNA) targeting several genes previously found to be associated with BPD such as NR3C1. Our results highlight the potentially important role played by miRNAs in the etiology of neuropsychiatric disorders such as BPD and the usefulness of using methylome-wide association studies to uncover such candidate genes. Moreover, they offer new understanding of the impact of maltreatments on biological processes leading to diseases and may ultimately result in the identification of relevant biomarkers.

High- or low-salt diet from weaning to adulthood: effect on insulin sensitivity in Wistar rats.

Because of conflicting results in the literature, further studies are needed to confirm an association between the degree of salt consumption and insulin sensitivity. The aim of this study was to measure insulin sensitivity in rats fed from weaning to adulthood with a low (LSD), normal (NSD), or high (HSD) salt diet. Body weight, carcass lipid content, blood glucose, nonesterified fatty acids, plasma insulin, plasma renin activity, and a glucose transporter (GLUT4) were measured. A euglycemic hyperinsulinemic clamp was used in 52 anesthetized rats. Body weight was higher in rats on LSD than in those on NSD (P<0.05) or HSD (P<0.001). Percentage fat carcass content was higher (P<0.05) in rats on LSD than in those on NSD. Basal plasma insulin and glucose levels were not altered (P>0.05) by salt consumption. Nonesterified fatty acids were lower in rats on HSD than in those on LSD (P<0.05) or NSD (P<0.01). Glucose uptake was lower in rats on LSD than in those on NSD (P<0.05) or HSD (P<0. 001). When a euglycemic hyperinsulinemic clamp was used on pair-weight rats, similar results were obtained, which suggests that the effect of LSD on insulin sensitivity was not due to higher body weight. GLUT4 in insulin-sensitive tissues was increased in rats on HSD except in the cardiac muscle. Captopril treatment partially reversed low insulin sensitivity in LSD rats, whereas losartan did not change it, which indicates that the effect of LSD on insulin sensitivity is angiotensin independent. In conclusion, the present results demonstrate that chronic dietary salt restriction induces a decrease in insulin sensitivity not associated with renin-angiotensin system activity or body weight changes.

Application of artificial enzymes to the problem of cocaine.

Cocaine mediates its reinforcing and toxic actions through a "loss of function" effect at multiple receptors. The difficulties inherent in blocking a pleiotropic blocker pose a great obstacle for the classical receptor-antagonist approach and have contributed to the failure-to-date to devise specific treatments for cocaine overdose and addiction. As an alternative, we have embarked on an investigation of catalytic antibodies, a programmable class of artificial enzyme, as "peripheral blockers"--agents designed to bind and degrade cocaine in the circulation before it partitions into the central nervous system to exert reinforcing or toxic effects. We synthesized transition-state analogs of cocaine's hydrolysis at its benzoyl ester, immunized mice, prepared hybridomas, and developed the first anti-cocaine catalytic antibodies with the capacity to degrade cocaine to non-reinforcing, non-toxic products. We subsequently identified several families of anti-cocaine catalytic antibodies and found that out most potent antibody, Mab15A10, possessed sufficient activity to block cocaine-induced reinforcement and sudden death in rodent models of addiction and overdose, respectively. With the potential to promote cessation of use, prolong abstinence, and provide a treatment for acute overdose, the artificial enzyme approach comprehensively responds to the problem of cocaine.

Response to psychotherapy in borderline personality disorder and methylation status of the BDNF gene.

Downregulation of brain-derived neurotrophic factor (BDNF) gene expression with corresponding increased methylation at specific promoters has been associated with stressful experiences in early life and may explain later adulthood psychopathology. We measured the percentage of methylation at BDNF CpG exons I and IV as well as plasma BDNF protein levels in 115 subjects with borderline personality disorder (BPD) and 52 controls. BPD subjects then underwent a 4-week course of intensive dialectical behavior therapy (I-DBT). BDNF methylation status and protein levels were re-assessed at the end of treatment. BPD subjects had significantly higher methylation status in both CpG regions than controls. In addition, the higher the number of childhood trauma, the higher was the methylation status. In BPD subjects, BDNF methylation significantly increased after I-DBT. Nonresponders accounted for the majority of this increase, whereas responders showed a decrease in methylation status over time. Accordingly, the changes in methylation status over time were significantly associated with changes in depression scores, hopelessness scores and impulsivity. No association was found between protein levels and BDNF methylation status. We here found a relationship between child maltreatment and higher DNA methylation of BDNF. These results moreover support the idea that these epigenetic marks may be changed through psychotherapeutic approaches and that these changes underline changes in cognitive functions.

Increased methylation of glucocorticoid receptor gene (NR3C1) in adults with a history of childhood maltreatment: a link with the severity and type of trauma.

Childhood maltreatment, through epigenetic modification of the glucocorticoid receptor gene (NR3C1), influences the hypothalamic-pituitary-adrenal axis (HPA axis). We investigated whether childhood maltreatment and its severity were associated with increased methylation of the exon 1(F) NR3C1 promoter, in 101 borderline personality disorder (BPD) and 99 major depressive disorder (MDD) subjects with, respectively, a high and low rate of childhood maltreatment, and 15 MDD subjects with comorbid post-traumatic stress disorder (PTSD). Childhood sexual abuse, its severity and the number of type of maltreatments positively correlated with NR3C1 methylation (P=6.16 × 10(-8), 5.18 × 10(-7) and 1.25 × 10(-9), respectively). In BPD, repetition of abuses and sexual abuse with penetration correlated with a higher methylation percentage. Peripheral blood might therefore serve as a proxy for environmental effects on epigenetic processes. These findings suggest that early life events may permanently impact on the HPA axis though epigenetic modifications of the NR3C1. This is a mechanism by which childhood maltreatment may lead to adulthood psychopathology.