Rythme veille-sommeil et dimensions cliniques dans le trouble de personnalité limite à l’adolescence

Cette thèse examine le rythme veille-sommeil et son association avec l’instabilité émotionnelle, l’agressivité et l’impulsivité dans le trouble de personnalité limite (TPL) à l’adolescence. Dans un premier temps, la revue de la littérature sur les perturbations objectives du sommeil dans le TPL a mis en lumière plusieurs difficultés similaires, évaluées par polysomnographie, à celles observées dans la dépression adulte. De 1980 à 2010, aucune recherche n’a examiné le rythme veille-sommeil, aucune n’a étudié les adolescents TPL et plusieurs n’ont pas contrôlé l’état dépressif comme facteur de confusion. De ce constat, il s’avérait pertinent de mener une étude sur le rythme veille-sommeil dans le TPL à l’adolescence en l’absence de dépression co-occurrente. L’adolescence comportant plusieurs caractéristiques physiologiques, psychologiques et sociales, tenir compte des aspects développementaux était essentiel. Dans un second temps, un protocole de recherche fût mis en place à la Clinique des troubles de l’humeur et le recrutement a été réalisé auprès d’adolescents souffrant d’un TPL et sans état dépressif actuel. Ils devaient porter pendant plus de neuf jours (période comprenant deux fins de semaine) un actigraphe, appareil non invasif évaluant l’alternance veille-sommeil dans l’environnement naturel. L’abandon précoce au traitement étant prévalent chez les patients TPL, la fiabilité de l’étude a été examinée afin de déterminer les raisons favorisant et celles nuisant au recrutement et à la collecte des données. La réflexion sur les aspects méthodologiques de l’étude actigraphique a permis d’expliquer les limites de ce type de protocole. Dans un troisième temps, le rythme veille-sommeil des adolescents TPL (n=18) a été caractérisé et comparé à celui des jeunes ayant un trouble bipolaire (n=6), trouble psychiatrique partageant plusieurs manifestations communes avec le TPL, et à celui des adolescents sans trouble de santé mentale (n=20). Les résultats suggèrent que l’adolescent TPL passe plus de temps en éveil durant la période de repos que les jeunes appartenant aux deux autres groupes. De plus, les adolescents TPL présentent une plus grande variabilité inter journalière des heures de lever et du temps total de sommeil que les autres adolescents. Ils se réveillent une heure de plus, et dorment donc une heure supplémentaire, que les adolescents sans trouble mental lors des journées sans routine. Dans un quatrième temps, les analyses corrélationnelles entre les données actigraphiques et les scores aux questionnaires auto-rapportés évaluant l’instabilité émotionnelle, l’agressivité et l’impulsivité suggèrent que plus l’adolescent TPL passe du temps éveillé alors qu’il est au lit, plus il déclare présenter des comportements agressifs, surtout physiques, durant le jour. En résumé, cette thèse contribue à la littérature scientifique en explorant pour la première fois le rythme veille-sommeil et son lien avec les manifestations symptomatiques dans le TPL à l’adolescence. Les résultats suggèrent fortement l’importance d’évaluer et de traiter les problèmes du rythme veille-sommeil que présentent ces jeunes lors de la prise en charge.This dissertation examines sleep-wake patterns and their associations with emotional instability, aggressiveness, and impulsivity in adolescents with Borderline Personality Disorder (BPD). First, a literature review showed in BPD adults similar objective sleep disturbances, as assessed with polysomnography, to those observed in adult depression. Between 1980 and 2010, no study has examined sleep-wake patterns, none has recruited BPD adolescents, and many did not control depression as a confounding factor. Considering these limitations, it became relevant to conduct a study on sleep-wake patterns in euthymic adolescents with BPD. Having a developmental perspective in mind is crucial since adolescence presents many physiological, psychological and social characteristics. Second, a research protocol was set up at the Mood Disorders Clinic. Adolescents with BPD and without current depression were recruited. They wore for nine days or more (period covering two weekends) an actigraph, a non-invasive device assessing ecologically sleep-wake patterns. Because treatment dropout is highly prevalent in BPD adolescents, study feasibility was examined to determine the reasons promoting and those interfering with recruitment and data collection. Reflections on methodological aspects of this study allowed explaining the limits of this type of research protocol. Third, sleep-wake patterns in BPD adolescents (n=18) was characterised. They were compared to youth with Bipolar Disorder (n=6), a mental disorder sharing many common manifestations with BPD, and to adolescents without mental disorder (n=20). Results suggest that BPD adolescents spend more time awake during the rest interval than teenagers from the two other groups. Furthermore, BPD adolescents present higher interdaily variability for rising time and total sleep time than the other adolescents. They wake up an hour later, therefore sleeping one more hour, than adolescents without mental disorder on schedule-free days. Fourth, correlation analyses between actigraphy data and self-report questionnaire scores assessing emotional instability, aggressiveness, and impulsivity suggest that time spent awake during time in bed is associated with more daily physical aggressiveness in BPD adolescents. To summarise, this dissertation adds to the current scientific literature by exploring for the first time sleep-wake patterns and its associations with symptomatic manifestations of BPD in adolescents. From these results, it is highly recommended to assess and treat their sleep-wake disturbances during their therapeutic care

Étude exploratoire et comparative du trouble bipolaire et du trouble de personnalité limite à l'adolescence

Actuellement, le diagnostic différentiel du trouble bipolaire (TB) et du trouble de personnalité limite (TPL) à l’adolescence s’avère difficile et complique le choix thérapeutique. Portant sur le TB et le TPL, ce mémoire fait le point sur la littérature scientifique adulte et adolescente, vérifie la faisabilité et présente les résultats d’une étude exploratoire portant sur les variables cliniques (instabilité émotionnelle, hostilité, impulsivité, tempraément) et le rythme veille-sommeil à l’adolescence. L’étude exploratoire comprend sept adolescents TB et huit TPL (12-17 ans), évalués par questionnaires autoadministrés pour les variables cliniques, et par actigraphie et agenda de sommeil pour le rythme veille-sommeil. Aucune différence significative n’existe entre les deux troubles pour les variables cliniques. En moyenne, les adolescents TB ont porté l'actigraphie pendant 9,9 jours et ont rempli un agenda de sommeil pendant 5,7 jours; chez les TPL, les chiffres sont respectivement 9,8 et 8,9 jours. Comparés aux TPL, les TB ont un plus grand intervalle d’éveil (p=0,035), ont un plus grand intervalle de sommeil (p>0,05), et ont une plus grand variabilité intrajournalière (p=0,04). Les données subjectives (agenda de sommeil) semblent refléter les données objectives (actigraphie) : aucune différence statistique n’est observée entre les deux mesures pour le délai d’endormissement, la durée du dernier réveil et le temps total de sommeil. La recension de la littérature montre un manque de données chez l’adolescent quant aux deux troubles. La faisabilité de l’étude est démontrée par la présence de résultats analysables. Ceci encourage la poursuite des recherches sur ces variables, afin de distinguer les deux psychopathologies à l’adolescence.Presently, differential diagnosis between bipolar disorder (BD) and borderline personality disorder (BPD) in adolescents remains difficult and affects therapeutic choices. This master’s thesis reviews current scientific literature, both in adults and adolescents. It examines feasibility and presents results of a study on clinical dimensions and endophenotypes in adolescent BD and BPD. Seven BD and eight BPD adolescents (12-17 years old) were evaluated by self-reported questionnaires for clinical variables (affective instability, impulsivity, hostility and temperament) and by actigraphy and sleep diary for sleep-wake circadian rhythm. No significant difference was found between BD and BPD for the clinical variables. BD adolescents wore actigraphic device for 9.9 days and completed the sleep diary for 5.7 days on average; for BPD subjects, the numbers were respectively 9.8 days and 8.9 days. Compared to BPD, BD patients had longer active interval (p=0.035), tended to sleep longer, and had more intradaily variability (p=0.04). Subjective data (sleep diary) and objective data (actigraphy) did not significantly differ on sleep onset latency, last awakening duration and total sleep time, which suggested that BD and BPD adolescents had a good estimate of their sleep patterns. Literature review showed a dearth of research done on adolescent BD and BPD. Feasibility of this study was verified, since data was successfully collected. Research on these variables should continue, so differential diagnosis can be done in adolescent BD and BPD

Highly Enantioselective Catalytic Asymmetric Synthesis of a (R)-Sibutramin Precursor

The first highly enantioselective, catalytic asymmetric synthesis of di-des-methylsibutramine 3 is described. Dienamide 10, prepared by acetic acid anhydride quenching of the condensation product of nitrile 4 with a methallyl magnesium chloride, proved to be an excellent substrate for ruthenium-catalyzed asymmetric hydrogenation with atropisomeric diphosphine ligands. Hydrogenation with a ruthenium/(R)- MeOBiPheP catalyst at S/C = 500, gave the chiral amide (R)-9 in 98.5% ee in almost quantitative yield. After acidic amide hydrolysis the desired amine (R)-3 was obtained without erosion of enantioselectivity. It is anticipated that the overall process will be amenable to large-scale production

Familial and Clinical Correlates in Depressed Adolescents with Borderline Personality Disorder Traits

Introduction: Chart review is a low-cost, but highly informative, method to describe symptoms, treatment and risk factors associated with Borderline Personality Disorder (BPD) and to adapt screening and intervention to clinical reality. Previous chart review studies report more aggressiveness/anger and psychotic features in youths with BPD. They show that adverse family environment and parental psychopathology constitute important factors for BPD pathology. Objectives: To examine clinical characteristics of depressed BPD adolescents (12-17 years old) outpatients according to gender and to explore variables which are associated with BPD traits. Methods: A retrospective chart review using the Child and Adolescent Version of the Retrospective Diagnostic Instrument for Borderlines was conducted on 30 depressed BPD adolescents with BPD traits and 28 non-BPD depressed patients without BPD traits. Participants who reached the C-DIB threshold for BPD were included in the BPD traits group. The Child and Adolescent Version of the Retrospective Diagnostic Interview for Borderlines was used to determine the presence of BPD. Comparisons analyses were performed using Pearson’s Chi-square test. Associated factors were determined using regression analyses. Results: BPD traits participants outpatients were characterised by higher family problems (parental psychopathology, parent disagreement/argument, parent-child relational problem), more aggressive symptoms, and higher rates of family intervention and hospitalisation. A number of familial factors (parental history of delinquency, substance use, or personality disorders, having siblings, parental disagreement/argument in boys) were associated with BPD symptomatologytraits. Attention seeking and problematic functioning (does not adapt well to group activities) were also associated with BPD traits. Discussion: Our study stresses the need to assess BPD traits in adolescent psychiatric evaluation, especially in presence of aggressive behaviours, family problems and attention seeking. Our results also highlight the importance of exploring family characteristics intervention in adolescents with BPD traits

Phenomenology, socio-demographic factors and outcome upon discharge of manic and mixed episodes in hospitalized adolescents

Background: The existence of bipolar disorder type I (BD-I) during adolescence is now clearly established whereas there are still some controversies on BD-II and BD-NOS diagnosis, mainly in Europe (O'Dowd in Br Med J 29, 2006). Little is known on the phenomenology and potential short-term prognosis factors of bipolar episodes in this age population. In particular, very few studies examine this issue on inpatients in the European context of free access to care. Objective: To describe the phenomenology of acute manic and mixed episodes in hospitalized adolescents and to analyse potential predictive factors associated with clinical improvement at discharge and length of hospitalization. Methods: A total of 80 subjects, aged 12–20 years, consecutively hospitalized for a manic or mixed episode. Socio-demographic and clinical data were extracted by reviewing patients' charts. We used a multivariate analysis to evaluate short-term outcome predictors. Results: The sample was characterized by severe impairment, high rates of psychotic features (N = 50, 62.5%), a long duration of stay (mean 80.4 days), and an overall good improvement (86% very much or much improved). Thirty-three (41.3 %) patients had a history of depressive episodes, 13 (16.3%) had manic or brief psychotic episodes but only 3 (3.7%) had a history of attention deficit/ hyperactivity disorders. More manic episodes than mixed episodes were identified in subjects with mental retardation (MR) and in subjects from migrant and/or low socio-economic families. Overall severity and female gender predicted better improvement in GAF scores. Poor insight and the existence of psychotic features predicted longer duration of stay. Conclusion: These results suggest that severe manic and mixed episodes in adolescents with BD-I need prolonged inpatient care to improve and that socio-cultural factors and MR should be examined more closely in youth with BD

Joint optimization of monitoring quality and replacement decisions in condition-based maintenance

The quality of condition monitoring is an important factor affecting the effectiveness of a condition-based maintenance program. It depends closely on implemented inspection and instrument technologies, and eventually on investment costs, i.e., a more accurate condition monitoring information requires a more sophisticated inspection, hence a higher cost. While numerous works in the literature have considered problems related to condition monitoring quality, (e.g., imperfect inspection models, detection and localization techniques, etc.) few of them focus on adjusting condition monitoring quality for condition-based maintenance optimization. In this paper, we investigate how such an adjustment can help to reduce the total cost of a condition-based maintenance program. The condition monitoring quality is characterized by the observation noises on the system degradation level returned by an inspection. A dynamic condition-based maintenance and inspection policy adapted to such a observation information is proposed and formulated based on Partially Observable Markov Decision Processes. The use and advantages of the proposed joint inspection and maintenance model are numerically discussed and compared to several inspection-maintenance policies through numerical examples

Policy framing and crisis narratives around food safety in Vietnam

While progress has been made recently in understanding food systems per se, much less is known about policies around those food systems. In this paper, we aim at understanding the food system policy context with the specific objective to look at policy dynamics—defined as the way policy agendas are identified, justified, and framed by decision-makers, and how they interact. Vietnam is used as a case study. Primary data were generated through face-to-face interviews complemented by an online survey. A policy framing approach was used to structure the research. The analysis reveals how the policy agenda is considered by many actors to be only partially evidence-based and highlights the extent to which the state government remains the most powerful actor in the setting of that agenda. The research also reveals the diffusion of the food safety crisis narrative beyond its original technical domain into a larger number of policy framings related to other issues of food systems, thus making it de facto the “center of gravity” of the current agenda on food systems in Vietnam. Yet, a comparison with data from other countries challenges this narrative, and reveals instead how the (legitimate) public concern about food safety is being instrumentalized by certain groups of actors to advance their own agenda. The implication of this “distorted” framing is the risk for the decision-makers to “overfocus” their attention on this short-term issue and lose sight of some other longer-term structural trends such as the emergence of obesity in Vietnamese urban population

Interactions between food environment and (Un)healthy consumption: Evidence along a rural-urban transect in Viet Nam

There is limited evidence on food environment in low and middle-income countries (LMICs) and the application of food environment frameworks and associated metrics in such settings. Our study examines how food environment varies across an urban-peri-urban-rural gradient from three sites in North Viet Nam and its relationship with child undernutrition status and household consumption of processed food. By comparing three food environments, we present a picture of the food environment in a typical emerging economy with specific features such as non-market food sources (own production and food transfers) and dominance of the informal retail sector. We combined quantitative data (static geospatial data at neighborhood level and household survey) and qualitative data (in-depth interviews with shoppers). We found that across the three study sites, traditional open and street markets remain the most important outlets for respondents. Contrary to the common concern that urban households are the major consumers of processed foods, peri-urban and rural areas on average had higher consumption of ultra-processed foods than in urban areas. The low price levels of processed foods and the presence of processed foods even among the traditional convenience stores, those in closest proximity to the rural households, offer potential explanations of this result. Regarding undernutrition, low retail diversity and a household’s dependence on own production have important implications for the high prevalence of child undernutrition in rural areas. Our findings add to the current discussion on the critical role of the food environment on nutrition, such as the potential link between economic marginalization and access to food, and the role of food supply channels in consumption of processed foods

MICROSCOPE mission analysis, requirements and expected performance

The MICROSCOPE mission aimed to test the Weak Equivalence Principle (WEP) to a precision of $10^{-15}$. The WEP states that two bodies fall at the same rate on a gravitational field independently of their mass or composition. In MICROSCOPE, two masses of different compositions (titanium and platinum alloys) are placed on a quasi-circular trajectory around the Earth. They are the test-masses of a double accelerometer. The measurement of their accelerations is used to extract a potential WEP violation that would occur at a frequency defined by the motion and attitude of the satellite around the Earth. This paper details the major drivers of the mission leading to the specification of the major subsystems (satellite, ground segment, instrument, orbit...). Building upon the measurement equation, we derive the objective of the test in statistical and systematic error allocation and provide the mission's expected error budget.Comment: References update