[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.

Early care in children with permanent hearing impairment.

The implementation of regional protocols for newborn hearing screening and early audiologic diagnosis represent the first step of the entire diagnostic, rehabilitative and prosthetic programme for children with permanent hearing impairment. The maximum benefit of early diagnosis can indeed be obtained only by prompt rehabilitation aimed at fostering the child's communicative, linguistic and cognitive development. Within the framework of the CMM 2013 project of the Ministry of Health entitled "Preventing Communication Disorders: a Regional Program for Early Identification, Intervention and Care of Hearing Impaired Children", the problems concerning the promotion of the global development of children with PHI through an early rehabilitation project based on shared knowledge and scientific evidence. In this project, our specific aim was to define the features and modes of access to a precise and specialised rehabilitation project for the small hearing-impaired child within three months from audiologic diagnosis. Three main recommendations relative to assessment and rehabilitation aspects of early care emerged from the study.

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.

NMR analysis of budding yeast metabolomics: a rapid method for sample preparation.

Here we propose the optimization of a rapid and reproducible protocol for intracellular metabolite extraction from yeast cells and their metabolic profiling by (1)H-NMR spectroscopy. The protocol reliability has been validated through comparison between the metabolome of cells in different phases of growth or with different genetic backgrounds.

Organización más allá de los algoritmos en la vía aérea dificultosa. "PENSAR globalmente y ACTUAR localmente" / Organization beyond the algorithms in the airway difficult. "THINK globally and ACT locally "

Objetivo: Evaluar el impacto sobre la tasa de complicaciones en la intubación orotraqueal con la implementación de un protocolo de actuación en el manejo de la vía aérea. Materiales y Métodos: Pacientes admitidos al Servicio de Terapia Intensiva polivalente entre agosto de 2012 y marzo de 2014, que requirieron intubación orotraqueal. Se utilizó un protocolo de actuación "Pensar globalmente y Actuar localmente" durante el proceso de preintubación, intubación y posintubación, que incluye valoración de las vías aéreas, planes de seguridad, optimización cardiovascular y pulmonar. Las complicaciones fueron: 1) intubación dificultosa, 2) intubación esofágica, 3) traumatismo de la vía aérea superior, 4) broncoaspiración, 5) arritmias cardíacas, 6) paro cardiocirculatorio. Se compararon las tasas de complicaciones durante dos períodos: Período 1 (P1): de agosto de 2010 a julio de 2012, en el que se realizó la intubación orotraqueal mediante la Secuencia de Intubación Rápida, y Período 2 (P2): de agosto de 2012 a marzo de 2014, en el que se implementó el protocolo "Pensar globalmente y Actuar localmente". Se evaluaron características demográficas, puntajes APACHE II y SOFA, complicaciones de la intubación, estancia en Terapia Intensiva y mortalidad. El análisis estadístico se realizó utilizando la media, la desviación estándar y la prueba de Fisher para las variables cuantitativas y la prueba de χ2 para las variables dicotó- micas. Se consideró significativa una probabilidad de error <5% (p <0,05). Resultados: 374 pacientes requirieron intubación orotraqueal: 180 (48,1%) en el P1 y 194 (51,8%) en el P2; edad: 59 ± 18 años (P1) y 61 ± 18 años (P2); APACHE II: 18 (P1) y 16 (P2); SOFA: 8 ± 2 y 7 ± 3, respectivamente; complicaciones: P1, 24 (13%), P2, 7 (3,6%) (p <0,001); intubación dificultosa: P1, 8 (33,3%), P2, 1 (14,2%) (p <0,005); intubación esofágica: P1, 3 (12,5%), P2, 1 (14,2%); traumatismo de la vía aérea superior: P1, 5 (21,3%), P2, 2 (28,5%); broncoaspiración: P1, 4 (16,6%), P2, 1 (14,2%); arritmias: P1, 3 (12,5%), P2,2 (28,5%), paro cardiocirculatorio: P1, 1 (4,1%), P2: 0. Estancia en Terapia Intensiva: 13.5 ± 3 días (P1) y 12.8 ± 1.2 días (P2). Mortalidad 10% (P1) y 6,2% (P2) (NS). Conclusión: La aplicación de un protocolo para el manejo de la vía aérea redujo, con significación estadística, la tasa de complicaciones, en particular, la intubación dificultosa. (AR)

Objective: To evaluate the impact of a protocol for the management of the airway on the complication rate in tracheal intubation. Materials and Methods: Patients requiring orotracheal intubation admitted to the Intensive Care Unit from August 2012 to March 2014 were included. The "Think globally and Act locally" protocol was used during pre-intubation, intubation and after intubation, including assessment of the airway, safety plans, cardiovascular and pulmonary optimization. Complications: 1) difficult intubation, 2) esophageal intubation, 3) upper airway trauma, 4) aspiration, 5) arrhythmias, 6) cardiac arrest. Rates of complications were compared during two periods: Period 1 (P1): from August 2010 to July 2012 where orotracheal intubation was conducted through rapid sequence intubation, and Period 2 (P2) from August 2012 to March 2014, where "Think globally and Act locally" protocol was implemented. Demographic characteristics, APACHE II and SOFA scores, complications of intubation, length of stay in the Intensive Care Unit, and mortality were evaluated. Statistical analyses were performed using mean, standard deviation, and Fisher test for quantitative variables and chi square test for dichotomous variables; a probability of error <5% (p <0,05) was considered significant. Results: 374 patients required tracheal intubation: 180 (48.1%) during P1 and 194 (51.8%) during P2; mean age: 59 ± 18 years (P1) and 61 ± 18 years (P2); APACHE II score: 18 (P1) and 16 (P2); SOFA score: 8 ± 2 (P1) and 7 ± 3 (P2); complications: P1, 24 (13%); P2, 7 (3.6%) (p <0.001); difficult intubation: P1, 8 (33.3%), P2, 1 (14.2%) (p <0.005); esophageal intubation: P1, 3 (12.5%), P2, 1 (14.2%), upper airway trauma: P1, 5 (21.3%), P2, 2 (28.5%); aspiration: P1, 4 (16.6%), P2, 1 (14.2%); arrhythmias: P1, 3 (12.5%), P2, 2 (28.5%); cardiac arrest: P1, 1 (4.1%), P2, 0; stay in the Intensive Care Unit: 13.5 ± 3 (P1) and 12.8 ± 1.2 days (P2); mortality: 10% (P1) and 6.2% (P2) (NS). Conclusion: Implementation of a protocol for the management of the airway decreased complications with statistical significance, including difficult intubation.(AR)

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.

[Psychometric properties of the Questionnaire de Fonctionnement Social in borderline personality disorder]. / Caractéristiques psychométriques du Questionnaire de Fonctionnement Social chez des patients borderline.

OBJECTIVE: Social functioning is a primordial aspect of mental health and it should be considered as an important outcome measure in psychiatric treatments and studies. Few short and simple assessment instruments are available in French. Recently, the Questionnaire de Fonctionnement Social (QFS) was developed to study social behavior of psychiatric patients. The QFS is a 16-item self-report questionnaire assessing the frequency of and the satisfaction with social behavior during the last two weeks. The aim of the present study is to explore QFS psychometric properties in a sample of patients with borderline personality disorder. METHODS: Eighty-six outpatients (78 women and eight men, mean age: 30.5+/-8.6) with borderline personality disorder and 100 healthy matched control subjects (89 women and 11 men, mean age: 30.2+/-7.7) completed the QFS. The convergent and divergent validities of the QFS were tested with the following instruments: Social Adaptation Self-Evaluation Scale (SASS), Brief Symptom Inventory (BSI), Beck Depression Inventory (BDI), Beck Hopelessness Scale (BHS) and a visual scale of suffering (EVS). Test-retest reliability of the QFS was calculated in a sub-sample of 28 subjects and its sensitivity to change was measured for 45 patients. RESULTS: Internal consistency of the QFS' global index was satisfying (Cronbach alpha from 0.59 to 0.84). Test-retest reliability of the QFS indexes ranged from 0.77 to 0.79 (intraclass correlation coefficient). Correlations between QFS and SASS demonstrated moderate convergent validity (r>0.59) whilst associations with others psychological measures (BSI, BDI, BHS, EVS) showed satisfying divergent validity (-0.42

[Influence of attention on an auditory-verbal learning test in schizophrenic patients]. / Influence de l'attention sur une épreuve d'apprentissage auditivo-verbal chez des patients schizophrènes.

Schizophrenic patients are known to feature alterations in their cognitive performances, principally in executive functions, attention and memory. In this last domain, studies have shown a relatively severe and global deficit, which can be assessed in chronic and first episode patients. It seems that the memory dysfunction is independent of age and intellectual level, but does correlate with negative psychopathology and global functioning. In the study of memory dysfunction, attentional capacities, information processing and symptomatology have to be considered as determining factors. It has been shown that patients with schizophrenia perform poorly in selective attention tasks and that this deficit may interfere with learning. In the same way, the slowing of information processing contributes to a superficial and incomplete learning. The impact of symptomatology has also to be considered, as negative and depressive symptoms are linked to mnesic performances. The majority of studies bearing on working memory and schizophrenia show an alteration of performances, but studies on long term memory are more equivocal. Procedural memory seems to be preserved, while declarative memory is impaired. These results support the hypothesis that in schizophrenia, memory processes that are consciously controlled are impaired, contrary to implicit learning which may be intact. Nevertheless, studies bearing on semantic memory and episodic memory show controversial results. Still, many authors argue that schizophrenic patients have difficulties in recalling learned material, specially when a delay or a interfering task are introduced in the test. Besides, the schizophrenic subjects do not use the semantic properties of the words, as well as the control subjects, when they have to learn a words list for example. The main goal of the present study was to examine the auditory-verbal learning capacities of 31 schizophrenic patients (20 men and 11 women, 19-56 years old), compared to 27 healthy subjects (11 men and 16 women, 23-56 years old). All subjects received an evaluation including the Rey Auditory-Verbal Learning Test, used to study the progressive acquisition of 15 disyllabic words which are successively orally presented five times to the subject. About forty-five minutes after the last of the five immediate recalls, the delayed recall is assessed and a percentage of retention is also calculated. Visual reasoning and attention capacities were studied with the Progressive Matrix and the d2 encumbrance test respectively. Global psychiatric symptomatology of the patients group was assessed with the Brief Psychiatric Rating Scale. Considering the literature existing on the verbal learning capacities of schizophrenic patients, it was expected that the patients would perform poorly and learn slower than controls. The initial learning of the material, which is a critical stage for schizophrenic patients, was studied with particular attention as well as the effect of the introduction of a delay upon the recall of the words list. A secondary objective of the study was to investigate the role of visual reasoning and attention upon auditory-verbal learning process. According to published studies, it is expected that schizophrenic patients manifest some impairment in the domains of visual reasoning and attention. The question is to know whether it alters performances in the auditory-verbal learning test or not. Finally, the links between clinical characteristics of the patients, like age and illness duration, and their learning performances were explored. Statistical analysis included first a descriptive analysis of data to examine differences between the two groups. Second, ANCOVAs were used in order to control the respective impact of educational level, attention capacities and verbal reasoning capacities upon learning performances. Third, Spearman's correlations were used to detect links between clinical characteristics of the patients and learning performances. The comparisons between patients and controls confirmed that schizophrenic patients scored less in the attentional and visual reasoning tasks. They also featured a lower educational level compared to the healthy subjects. In the auditory-verbal learning test, the patients showed altered performances in the five recalls, as well as in the delayed recall and for the retention percentage. In order to control the impact of educational level, attentional and visual reasoning capacities, these parameters were introduced in the statistical analyses. Educational level did not influence memory alterations in the schizophrenic group. However, attention and, to a lesser extend, visual reasoning had an impact on the comparison of memory scores: when controlling attention, almost no significant group effect remained. Finally, the exploratory analyses of links between clinical characteristics and memory only revealed the presence of a significant negative correlation between illness duration and learning performances. Thus, the analyze of data showed that schizophrenic subjects featured poor performances in the domains of attention, verbal reasoning and auditory-verbal memory. Further analyses taking into account group differences on attention suggest that the impairment featured by schizophrenic patients in the domain of verbal memory strongly relies on an attentional deficit. These results are discussed according to the existing literature and methodological limitations. Clinical implications are also discussed.

A study of visual and auditory verbal working memory in schizophrenic patients compared to healthy subjects.

Impaired working memory (WM) performance is considered as a central feature of schizophrenia. Divided into two components, verbal and spatial, WM has been shown to involve frontal and parietal regions. Verbal WM can be tested either visually or aurally. The present study aimed to test schizophrenic patients in both visual and auditory verbal WM in order to assess a possible distinct pattern of alteration of these two modalities. Twenty-four schizophrenic patients and 24 healthy controls were compared with 2-back continuous visual and auditory verbal WM testing. Both groups were also tested on a neuropsychological battery including Wisconsin Card Sorting Test (WCST). Schizophrenic patients were less efficient in both verbal WM tests. When taking age and educational level as covariates and both WM modalities as dependent variables, there was no differential effect of modalities across groups. In further exploratory analyses, partial correlations brought association between verbal WM and psychosocial adaptation, WCST and length of illness. These results suggest a similar pattern of alteration of both modalities of verbal WM in schizophrenic patients. The implications of this finding are discussed.

Can caffeine antagonize alcohol-induced performance decrements in humans?

Design aspects and results of experiments that investigated the effects of caffeine on alcohol-induced performance decrements in humans are discussed. Simple conclusions concerning those outcomes are unwarranted because they seem to depend on the tasks used and the dosages of both drugs, with both antagonism and potentiation of alcohol-induced effects having been reported. Results indicate that legally intoxicated individuals cannot antagonize alcohol-induced, driving-related decrements with caffeine prior to driving an automobile, thought to be the major behavior for which caffeine is used in attempts to antagonize alcohol-induced decrements. We offer suggestions for research concerning subjects' habitual use or nonuse of caffeine and typical alcohol consumption levels, the interval between alcohol and caffeine ingestion, and the effects of caffeine and alcohol alone on performance tasks. We also suggest that statistical analyses should allow for a differentiation of results in which caffeine partially offsets an alcohol-induced decrement from more positive results in which caffeine returns functioning to its normal level.