Évaluation d’un programme novateur de réadaptation par les arts de la scène pour des jeunes présentant un trouble psychiatrique stabilisé : le programme Espace de Transition

L’objectif de cette thèse était d’évaluer Espace de Transition (ET), un programme novateur d’intervention par les arts de la scène visant à favoriser la réadaptation psychosociale d’adolescents et de jeunes adultes présentant des troubles mentaux stabilisés et à diminuer la stigmatisation des individus aux prises avec des problèmes de santé mentale. Ce programme a été conçu par une équipe de cliniciens du département de psychiatrie du Centre hospitalier universitaire Ste-Justine, en collaboration avec des artistes professionnels, et est livré depuis le printemps 2009. L’évaluation du programme ET a été conduite de manière indépendante, selon des approches collaborative et naturaliste et en usant de méthodes mixtes. Les données de recherche ont été recueillies avant pendant et après le programme auprès de l’ensemble des participants à deux sessions distinctes (N = 24), de même qu’auprès des deux artistes instructeurs, de la psychoéducatrice responsable du soutien clinique, ainsi que des psychiatres et autres intervenants ayant référé des participants (N=11). Des entrevues semi-structurées individuelles et de groupe, des observations directes et des questionnaires ont servi à recueillir les données nécessaires à l’évaluation. Des analyses quantitatives de variance, ainsi que des analyses qualitatives thématiques ont été réalisées et leurs résultats ont été interprétés de manière intégrée. Le premier chapitre empirique de la thèse relate l’évaluation de la mise en œuvre du programme ET. Cette étude a permis de constater que le programme avait rejoint des participants correspondant de près à la population visée et que ceux-ci présentaient globalement des niveaux élevés d’assiduité, d’engagement et d’appréciation du programme. L’évaluation de la mise en œuvre a en outre permis de conclure que la plupart des composantes du programme identifiées a priori comme ses paramètres essentiels ont été livrées tel que prévu par les concepteurs et que la plupart d’entre elles ont été largement appréciées et jugées pertinentes par les participants et les autres répondants consultés. Le second chapitre empirique consiste en un article portant sur l’évaluation des effets du programme ET relativement à l’atteinte de trois de ses objectifs intermédiaires, soient l’amélioration 1) du fonctionnement global, 2) du confort relationnel et des compétences sociales, ainsi que 3) de la perception de soi des participants présentant des troubles mentaux. Les résultats de cette étude ont révélé des changements significatifs et positifs dans le fonctionnement global des participants suite au programme, tel qu’évalué par les cliniciens référents et partiellement corroboré par les participants eux-mêmes. Des améliorations en ce qui concerne le confort relationnel, les compétences sociales et la perception de soi ont également été objectivées chez une proportion substantielle de participants, bien que celles-ci ne se soient pas traduites en des différences significatives décelées par les analyses quantitatives de groupe. Le troisième et dernier chapitre empirique de la thèse relate une étude exploratoire des mécanismes sous-tendant les effets du programme ET ayant conduit à l’élaboration inductive d’une théorie d’action de ce programme. Cette investigation qualitative a révélé quatre catégories de mécanismes, soient des processus de 1) gain d’expérience et de gratification sociales, 2) de désensibilisation par exposition graduelle, 3) de succès et de valorisation, et 4) de normalisation. Cette étude a également permis de suggérer les caractéristiques et composantes du programme qui favorisent la mise en place ou l’impact de ces mécanismes, tels l’environnement et l’animation non cliniques du programme, la composition hétérogène des groupes de participants, le recours aux arts de la scène, ainsi que la poursuite d’une réalisation collective et son partage avec un public extérieur au programme. Globalement, les études présentées dans la thèse appuient la pertinence et le caractère prometteur du programme ET, tout en suggérant des pistes d’amélioration potentielle pour ses versions ultérieures. Par extension, la thèse soutient l’efficacité potentielle d’interventions réadaptatives mettant en œuvre des composantes apparentées à celles du programme ET pour soutenir le rétablissement des jeunes aux prises avec des troubles mentaux.

Analyse des facteurs biodémographiques, sociéconomiques et familiaux de la longévité exceptionnelle

La recherche des facteurs de longévité gagne en intérêt dans le contexte actuel du vieillissement de la population. De la littérature portant sur la longévité et la mortalité aux grands âges, un constat émerge : bien que les déterminants associés à la survie humaine soient multiples, l'environnement familial aurait un rôle déterminant sur la mortalité et sur l'atteinte des âges avancés. Dès lors, l'objectif de cette thèse est d'évaluer les déterminants de la survie exceptionnelle et d'examiner le rôle des aspects familiaux, en début de vie et à l'âge adulte, dans les différentiels de durée de vie. Plus spécifiquement, elle vise à : (1) examiner la similarité des âges au décès entre frères, soeurs et conjoints afin d'apprécier l'ampleur de la composante familiale de la longévité; (2) explorer, d'un point de vue intrafamilial, les conséquences à long terme sur la survie des variables non partagées issues de la petite enfance tels l'âge maternel à la reproduction, le rang de naissance et la saison de naissance; et (3) s'interroger sur le rôle protecteur ou délétère de l’environnement et du milieu familial d'origine dans l’enfance sur l'atteinte des grands âges et dans quelle mesure le statut socioéconomique parvient à médiatiser la relation. Cette analyse s'appuie sur le jumelage des recensements canadiens et des actes de décès de l’état civil québécois et emploie des données québécoises du 20e siècle issues de deux échantillons distincts : un échantillon aléatoire représentatif de la population provenant du recensement canadien de 1901 ainsi qu’un échantillon de frères et soeurs de centenaires québécois appartenant à la même cohorte. Les résultats, présentés sous forme d'articles scientifiques, ont montré, en outre, que les frères et soeurs de centenaires vivent plus longtemps que les individus appartenant aux mêmes cohortes de naissance, reflétant la contribution d'une robustesse commune, mais également celle de l'environnement partagé durant la petite enfance. Ces analyses ont également témoigné d'un avantage de survie des conjoints des centenaires, soulignant l'importance d'un même environnement à l'âge adulte (1er article). De plus, nos travaux ont mis de l'avant la contribution aux inégalités de longévité des variables biodémographiques issues de l'environnement non partagé telles que l'âge maternel à la reproduction, le rang de naissance et la saison de naissance, qui agissent et interagissent entre elles pour créer des vulnérabilités et influer sur l'atteinte des âges exceptionnels (2e article). Enfin, une approche longitudinale a permis de souligner la contribution du milieu social d'origine sur la longévité, alors que les individus issus d’un milieu socioéconomique défavorisé pour l'époque (milieu urbain, père ouvrier) vivent moins longtemps que ceux ayant vécu dans un environnement socioéconomique favorable (milieu rural, fermier), résultat d'une potentielle accumulation des avantages liée à la reproduction du statut social ou d'une programmation précoce des trajectoires de santé. L’influence est toutefois moindre pour les femmes et pour les frères de centenaires et s'exprime, dans ce cas, en partie par l'effet de la profession à l'âge adulte (3e article).

Estudio de asociación entre genotipo de DAT1 y transtorno por déficit de atención / hiperactividad

Introducción: El TDAH tiene un componente genético importante; el gen de transportador de Dopamina (DAT1) se ha asociado con susceptibilidad al TDAH y con sus endofenotipos. El VNTR de 40pb en la región 3’UTR aumenta la expresión del DAT1. En Colombia no hay ningún estudio previo que indique evidencia de la asociación genética entre TDAH y el gen DAT1. Objetivo: Determinar asociación entre el VNTR del DAT1 y el fenotipo y/o endofenotipos del TDAH. Métodos: Se seleccionaron 73 pacientes con TDAH y 75 controles, se valoró en los casos inteligencia y funciones ejecutivas. Mediante (PCR) se amplificó el VNTR DAT1. Se establecieron estadísticos genético poblacionales, análisis de asociación y de regresión logística entre las pruebas neuropsicológicas y genotipo. Resultado: El polimorfismo del DAT1 no mostró asociación con TDAH, ni con alteraciones en las funciones ejecutivas. El genotipo 10/10 del VNTR DAT1 se encontró asociado con el índice de velocidad de procesamiento (p <0,05). En el subgrupo hiperactividad hubo asociación con algunas subpruebas de flexibilidad cognitiva, número de respuestas correctas, total de errores, número de respuestas perseverativas (p ≤ 0.01). En el subgrupo mixto se asoció con índice de comprensión verbal (p <0,05). Conclusiones: No hubo asociación entre el polimorfismo VNTR (DAT1) y el fenotipo de TDAH. Se encontraron asociaciones entre genotipo y algunos test de flexibilidad cognitiva e índice de comprensión verbal. Se establecieron los estadísticos genético poblacionales de este polimorfismo para la población analizada, el cual corresponde al primer reporte de una muestra de nuestro país.

A Bayesian approach to disease gene location using allelic association

A Bayesian approach to analysing data from family-based association studies is developed. This permits direct assessment of the range of possible values of model parameters, such as the recombination frequency and allelic associations, in the light of the data. In addition, sophisticated comparisons of different models may be handled easily, even when such models are not nested. The methodology is developed in such a way as to allow separate inferences to be made about linkage and association by including theta, the recombination fraction between the marker and disease susceptibility locus under study, explicitly in the model. The method is illustrated by application to a previously published data set. The data analysis raises some interesting issues, notably with regard to the weight of evidence necessary to convince us of linkage between a candidate locus and disease.

Reducing implicit prejudice by blurring intergroup boundaries

In two experiments we examined whether and when blurring intergroup boundaries reduces implicit prejudice. In Experiment 1 we observed that when participants first completed a task in which they generated characteristics that overlapped between an ingroup and an outgroup they showed less implicit bias as measured by an Implicit Association Test. In Experiment 2 we found that the effectiveness of blurring intergroup boundaries for reducing implicit bias was moderated by pretask levels of ingroup identification. We discuss these findings in the context of extending differentiation-based interventions for reducing explicit bias to the domain of implicit attitudes.

Sequential methods for pharmacogenetic studies

A study or experiment can be described as sequential if its design includes one or more interim analyses at which it is possible to stop the study, having reached a definitive conclusion concerning the primary question of interest. The potential of the sequential study to terminate earlier than the equivalent fixed sample size study means that, typically, there are ethical and economic advantages to be gained from using a sequential design. These advantages have secured a place for the methodology in the conduct of many clinical trials of novel therapies. Recently, there has been increasing interest in pharmacogenetics: the study of how DNA variation in the human genome affects the safety and efficacy of drugs. The potential for using sequential methodology in pharmacogenetic studies is considered and the conduct of candidate gene association studies, family-based designs and genome-wide association studies within the sequential setting is explored. The objective is to provide a unified framework for the conduct of these types of studies as sequential designs and hence allow experimenters to consider using sequential methodology in their future pharmacogenetic studies.

The effects of flavonoid and other polyphenol consumption on cognitive performance: A systematic research review of human experimental and epidemiological studies

Literature reviews suggest flavonoids, a sub-class of polyphenols, are beneficial for cognition. This is the first review examining the effect of consumption of all polyphenol groups on cognitive function. Inclusion criteria were polyphenol vs. control interventions and epidemiological studies with an objective measure of cognitive function. Participants were healthy or mildly cognitively impaired adults. Studies were excluded if clinical assessment or diagnosis of Alzheimer’s disease, dementia, or cognitive impairment was the sole measure of cognitive function, or if the polyphenol was present with potentially confounding compounds such as caffeine (e.g. tea studies) or Ginkgo Biloba. 28 studies were identified; 4 berry juice studies, 4 cocoa studies, 13 isoflavone supplement studies, 3 other supplement studies, and 4 epidemiological surveys. Overall, 16 studies reported cognitive benefits following polyphenol consumption. Evidence suggests that consuming additional polyphenols in the diet can lead to cognitive benefits, however, the observed effects were small. Declarative memory and particularly spatial memory appear most sensitive to polyphenol consumption and effects may differ depending on polyphenol source. Polyphenol berry fruit juice consumption was most beneficial for immediate verbal memory, whereas isoflavone based interventions were associated with significant improvements for delayed spatial memory and executive function. Comparison between studies was hampered by methodological inconsistencies. Hence, there was no clear evidence for an association between cognitive outcomes and polyphenol dose response, duration of intervention, or population studied. In conclusion, however, the findings do imply that polyphenol consumption has potential to benefit cognition both acutely and chronically.

Weighted alpha-rate dominating sets in social networks

We are looking into variants of a domination set problem in social networks. While randomised algorithms for solving the minimum weighted domination set problem and the minimum alpha and alpha-rate domination problem on simple graphs are already present in the literature, we propose here a randomised algorithm for the minimum weighted alpha-rate domination set problem which is, to the best of our knowledge, the first such algorithm. A theoretical approximation bound based on a simple randomised rounding technique is given. The algorithm is implemented in Python and applied to a UK Twitter mentions networks using a measure of individuals’ influence (klout) as weights. We argue that the weights of vertices could be interpreted as the costs of getting those individuals on board for a campaign or a behaviour change intervention. The minimum weighted alpha-rate dominating set problem can therefore be seen as finding a set that minimises the total cost and each individual in a network has at least alpha percentage of its neighbours in the chosen set. We also test our algorithm on generated graphs with several thousand vertices and edges. Our results on this real-life Twitter networks and generated graphs show that the implementation is reasonably efficient and thus can be used for real-life applications when creating social network based interventions, designing social media campaigns and potentially improving users’ social media experience.

Radically open-dialectical behavior therapy for adult anorexia nervosa: feasibility and outcomes from an inpatient program

Background Anorexia Nervosa (AN) is a highly life-threatening disorder that is extremely difficult to treat. There is evidence that family-based therapies are effective for adolescent AN, but no treatment has been proven to be clearly effective for adult AN. The methodological challenges associated with studying the disorder have resulted in recommendations that new treatments undergo preliminary testing prior to being evaluated in a randomized clinical trial. The aim of this study was to provide preliminary evidence on the effectiveness of a treatment program based on a novel adaptation of Dialectical Behavior Therapy (DBT) for adult Anorexia Nervosa (Radically Open-DBT; RO-DBT) that conceptualizes AN as a disorder of overcontrol. Methods Forty-seven individuals diagnosed with Anorexia Nervosa-restrictive type (AN-R; mean admission body mass index = 14.43) received the adapted DBT inpatient program (mean length of treatment = 21.7 weeks). Results Seventy-two percent completed the treatment program demonstrating substantial increases in body mass index (BMI; mean change in BMI = 3.57) corresponding to a large effect size (d = 1.91). Thirty-five percent of treatment completers were in full remission, and an additional 55% were in partial remission resulting in an overall response rate of 90%. These same individuals demonstrated significant and large improvements in eating-disorder related psychopathology symptoms (d = 1.17), eating disorder-related quality of life (d = 1.03), and reductions in psychological distress (d = 1.34). Conclusions RO-DBT was associated with significant improvements in weight gain, reductions in eating disorder symptoms, decreases in eating-disorder related psychopathology and increases in eating disorder-related quality of life in a severely underweight sample. These findings provide preliminary support for RO-DBT in treating AN-R suggesting the importance of further evaluation examining long-term outcomes using randomized controlled trial methodology.

Enhanced effects of combined cognitive bias modification and computerised cognitive behaviour therapy on social anxiety

This study examines whether combined cognitive bias modification for interpretative biases (CBM-I) and computerised cognitive behaviour therapy (C-CBT) can produce enhanced positive effects on interpretation biases and social anxiety. Forty socially anxious students were randomly assigned into two conditions, an intervention group (positive CBM-I + C-CBT) or an active control (neutral CBM-I + C-CBT). At pre-test, participants completed measures of social anxiety, interpretative bias, cognitive distortions, and social and work adjustment. They were exposed to 6 × 30 min sessions of web-based interventions including three sessions of either positive or neutral CBM-I and three sessions of C-CBT, one session per day. At post-test and two-week follow-up, participants completed the baseline measures. A combined positive CBM-I + C-CBT produced less negative interpretations of ambiguous situations than neutral CBM-I + C-CBT. The results also showed that both positive CBM-I + C-CBT and neutral CBM-I + C-CBT reduced social anxiety and cognitive distortions as well as improving work and social adjustment. However, greater effect sizes were observed in the positive CBM-I + C-CBT condition than the control. This indicates that adding positive CBM-I to C-CBT enhanced the training effects on social anxiety, cognitive distortions, and social and work adjustment compared to the neutral CBM-I + C-CBT condition.

Reproducibility of the online Food4Me food-frequency questionnaire for estimating dietary intakes across Europe

Background: Accurate dietary assessment is key to understanding nutrition-related outcomes and is essential for estimating dietary change in nutrition-based interventions. Objective: The objective of this study was to assess the pan-European reproducibility of the Food4Me food-frequency questionnaire (FFQ) in assessing the habitual diet of adults. Methods: Participantsfromthe Food4Me study, a 6-mo,Internet-based, randomizedcontrolled trial of personalized nutrition conducted in the United Kingdom, Ireland, Spain, Netherlands, Germany, Greece, and Poland were included. Screening and baseline data (both collected before commencement of the intervention) were used in the present analyses, and participants were includedonly iftheycompleted FFQs at screeningand at baselinewithin a 1-mo timeframebeforethe commencement oftheintervention. Sociodemographic (e.g., sex andcountry) andlifestyle[e.g.,bodymass index(BMI,inkg/m2)and physical activity] characteristics were collected. Linear regression, correlation coefficients, concordance (percentage) in quartile classification, and Bland-Altman plots for daily intakes were used to assess reproducibility. Results: In total, 567 participants (59% female), with a mean 6 SD age of 38.7 6 13.4 y and BMI of 25.4 6 4.8, completed bothFFQswithin 1 mo(mean 6 SD: 19.26 6.2d).Exact plus adjacent classification oftotal energy intakeinparticipants was highest in Ireland (94%) and lowest in Poland (81%). Spearman correlation coefficients (r) in total energy intake between FFQs ranged from 0.50 for obese participants to 0.68 and 0.60 in normal-weight and overweight participants, respectively. Bland-Altman plots showed a mean difference between FFQs of 210 kcal/d, with the agreement deteriorating as energy intakes increased. There was little variation in reproducibility of total energy intakes between sex and age groups. Conclusions: The online Food4Me FFQ was shown to be reproducible across 7 European countries when administered within a 1-mo period to a large number of participants. The results support the utility of the online Food4Me FFQ as a reproducible tool across multiple European populations. This trial was registered at clinicaltrials.gov as NCT01530139.

HTR1B and HTR2C in autism spectrum disorders in Brazilian families

Autism spectrum disorders (ASD) is a group of behaviorally defined neuro developmental disabilities characterized by multiple genetic etiologies and a complex presentation. Several studies suggest the involvement of the serotonin system in the development of ASD, but only few have investigated serotonin receptors. We have performed a case-control and a family-based study with 9 polymorphisms mapped to two serotonin receptor genes (HTR1B and HTR2C) in 252 Brazilian male ASD patients of European ancestry. These analyses showed evidence of undertransmission of the HTR1B haplotypes containing alleles -161G and -261A at HTR1B gene to ASD (P=0.003), but no involvement of HTR2C to the predisposition to this disease. Considering the relatively low level of statistical significance and the power of our sample, further studies are required to confirm the association of these serotonin-related genes and ASD. (C) 2008 Elsevier B.V. All rights reserved.

Genetic and Functional Evidence Implicating DLL1 as the Gene That Influences Susceptibility to Visceral Leishmaniasis at Chromosome 6q27

Background. Visceral leishmaniasis (VL) is caused by Leishmania donovani and Leishmania infantum chagasi. Genome-wide linkage studies from Sudan and Brazil identified a putative susceptibility locus on chromosome 6q27. Methods. Twenty-two single-nucleotide polymorphisms (SNPs) at genes PHF10, C6orf70, DLL1, FAM120B, PSMB1, and TBP were genotyped in 193 VL cases from 85 Sudanese families, and 8 SNPs at genes PHF10, C6orf70, DLL1, PSMB1, and TBP were genotyped in 194 VL cases from 80 Brazilian families. Family-based association, haplotype, and linkage disequilibrium analyses were performed. Multispecies comparative sequence analysis was used to identify conserved noncoding sequences carrying putative regulatory elements. Quantitative reverse-transcription polymerase chain reaction measured expression of candidate genes in splenic aspirates from Indian patients with VL compared with that in the control spleen sample. Results. Positive associations were observed at PHF10, C6orf70, DLL1, PSMB1, and TBP in Sudan, but only at DLL1 in Brazil (combined P = 3 x 10(-4) at DLL1 across Sudan and Brazil). No functional coding region variants were observed in resequencing of 22 Sudanese VL cases. DLL1 expression was significantly (P = 2 x 10(-7)) reduced (mean fold change, 3.5 [SEM, 0.7]) in splenic aspirates from patients with VL, whereas other 6q27 genes showed higher levels (1.27 x 10(-6) < P < .01) than did the control spleen sample. A cluster of conserved noncoding sequences with putative regulatory variants was identified in the distal promoter of DLL1. Conclusions. DLL1, which encodes Delta-like 1, the ligand for Notch3, is strongly implicated as the chromosome 6q27 VL susceptibility gene.