Background: Major depression is one of the most prevalent, disabling, and costly illnesses worldwide. Despite a 400% increase in antidepressant medication use since 1988, fewer than half of treated depression patients experience a clinically meaningful reduction in symptoms and uncertainty exists regarding how to successfully obtain symptom remission. Identifying homogenous subgroups based on clinically observable characteristics could improve the ability to efficiently predict who will benefit from which treatments. Methods: Latent class analysis and latent transition analysis (LTA) were applied to data from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study to explore how to efficiently identify subgroups comprised of the multiple dimensions of depression and examine changes in subgroup membership during treatment. The specific aims of this dissertation were to: 1) evaluate latent depression subgroups for men and women prior to antidepressant treatment; 2) examine transitions in these subgroups over 12 weeks of citalopram treatment; and 3) examine differences in functional impairment between women’s depression subgroups throughout treatment. Results: Four subgroups of depression were identified for men and women throughout this work. Men’s subgroups were distinguished by depression severity and psychomotor agitation and retardation. Severity, appetite changes, insomnia, and psychomotor disturbances characterized women’s subgroups. Psychiatric comorbidities, especially anxiety disorders, were related to increased odds of membership in baseline moderate and severe depression subgroups for men and women. After 12 weeks of citalopram treatment, depression severity and psychomotor agitation were related to men’s chances of improving. Severity and appetite changes were related to women’s likelihood of improving during treatment. When functional impairment was incorporated in LTA models for women, baseline functional impairment levels were related to both depression subgroups at baseline and chances of moving to a different depression subgroup after treatment. Conclusion: Depression severity, psychomotor disturbances, appetite changes, and insomnia distinguished depression subgroups in STAR*D. Gender, functional impairment, comorbid psychiatric disorders, and likelihood of transitioning to subgroups characterized by symptom improvement differed between these subgroups. The results of this work highlight how relying solely on summary symptom rating scale scores during treatment obscures changes in depression that might be informative for improving treatment response.

No description available.

Sleep is an essential part of life, and obtaining quality sleep is important for various areas of functioning. Behaviors to promote sleep include physical activity, managing stress, reducing anxiety symptoms, maintaining a consistent sleep schedule, and obtaining bright light exposure. Many of these behaviors overlap with benefits observed from pet ownership (PO). The present study aimed to examine the relation between PO and sleep as well as moderators and mediators of this relation. Four research questions were examined: 1) Is PO significantly related to sleep? 2) Does gender moderate the relation between PO and sleep? 3) Do sleep-promoting behaviors (i.e., physical activity, perceived stress, anxiety symptoms, bright light exposure, sleep-wake variability) mediate the relation between PO and sleep? 4) Do the mediating effects of the sleep-promoting behaviors on the relation between PO and sleep depend on the regularity of walking? Participants (N = 1,250; 80.8% White; 50.5% men) residing in the United States reported on their sleep, physical activity, perceived stress, anxiety symptoms, and light exposure. Participants were 25.5% non-pet owners (NPO), 24.1% cat-only owners (CO), 25.7% dog-only owners (DO), and 24.7% owned dogs and cats (DCO). Data analyses included ANCOVA, Moderation, Parallel Mediation, and Conditional Process Modeling. Key findings included that PO was significantly related to sleep, with NPO sleeping worse than PO (CO/DO/DCO combined) and DCO reporting the best sleep of all four PO groups. The relation between PO and sleep did not significantly differ for men and women. The relation was significantly mediated by anxiety symptoms, perceived stress, light exposure, and sleep-wake variability depending on the groups compared and scoring methods used. Anxiety symptoms and perceived stress were the most robust mediators of the relation between PO and sleep. Walking regularity did not change the mediating effects between PO and sleep. This study is one of the first to examine daytime mechanisms of the relation between PO and sleep. The findings provide a foundation for future research examining how the integration of PO and sleep-promoting behaviors can improve adherence to sleep health recommendations, thus improving owners’ sleep.

This study investigated nicotine conditioned place preference (CPP) in two different ages of adolescence using a rodent model of schizophrenia. Both 2- and 3-chambered CPP apparatuses were used to test whether the CPP was due to an aversion to the white chamber. Animals were neontally treated with the dopamine D2/D3 agonist, quinpirole, or saline and raised to either early postweanling age (P 22) or adolescence (P 29). Rats were conditioned to prefer the white chamber using nicotine. Results showed that nicotine induced CPP and appeared to alleviate an increased stress response in D2 primed animals, which appeared to diminish over time. Additionally, adult D2 and non-D2 primed rats were tested on the elevated T-maze. Results revealed that D2 primed rats demonstrated a significant increase in unconditioned fear. This study showed that nicotine induced CPP in D2 and non-D2 primed rats regardless of age, and D2 primed rats appear to demonstrate an increase in stress levels that was alleviated by nicotine.

The purpose was to examine the effect of a self-care educational intervention on nursing student resilience and thus the potential for compassion fatigue, depersonalization, burnout, depression, and inadequate self-care. A one-group pretest-posttest research design was applied to a convenience sample of 104 nursing students near the end of their last semester in a baccalaureate nursing program. The measurements were demographics, a psychometric resilience scale, program evaluation, and reflection question. The intervention was a standardized, intensive 30 min training program on the high degree of stress and burnout nurses face and the core self-care methods that can promote resilience to these hazards. The educational intervention had a strong positive effect on resilience scores (effect size of r=72%; p < 0.05). Eighty-six percent of the participants believed that the intervention increased their capabilities for self-care, especially in sleep, spending time outside, hydration, nutrition, and physical stretching exercises but not in journaling. Eighty-one percent stated that they would be likely to seek professional help if needed. Although this study must be repeated in other samples before it be implemented with full confidence, the standardized, high intensity, short duration, resilience training session can be recommended to nursing programs just prior to graduation and to hospitals for nurse orientation programs.

La relation entre troubles mentaux graves et violence criminelle, bien qu’étant la cible de nombreuses recherches, n’est, à l’heure actuelle, pas totalement établie. Ainsi, en explorant la piste d’une tierce partie – à savoir la présence d’un trouble d’abus ou de dépendance à une substance psychoactive – la présente étude vise à améliorer la compréhension du processus de passage à l’acte violent au sein des carrières criminelles des personnes atteintes de troubles psychiatriques. Sur la base des récits narratifs de neuf usagés d’un service de psychiatrie légale présentant un parcours de violence, les données récoltées ont pour objectif d’explorer la carrière criminelle des contrevenants atteints de troubles mentaux graves. Ainsi, il s’agit d’approfondir le sens que représentent leurs actes, de comprendre l’implication des substances psychotropes au sein de cette dynamique en déterminant l’enchaînement des éléments entrant en interaction, et de supposer quelles dimensions sont les plus à risques quant au passage à l’acte violent. La première contribution, comme d’autres avant nous, est de faire état d’un lien entre l’abus de substances psychoactives et la perpétration d’actes criminels, notamment violents, au sein des carrières criminelles des personnes présentant des troubles mentaux graves. Deuxièmement, l’identification des facteurs de risques et de facilitateurs cliniques, contextuels, historiques et relationnels nous ont permis de constater que le processus du passage à l’acte criminel va plus loin que l’interaction des troubles mentaux graves et de l’abus de substances. Troisièmement, l’approche qualitative de l’étude des carrières criminelles, trop peu utilisée dans les précédentes recherches portant sur le sujet, a permis d’étayer et de nuancer le modèle typologique de Hodgins et coll. (1998) présentant le parcours de vie des criminels atteints de troubles mentaux graves. Finalement, cette recherche permet d’orienter le développement de programmes d’interventions visant la réinsertion au sein des structures médico-légales. / The relationship between severe mental illness and criminal violence is strongly studied in the field. However, the link between these two elements is still misunderstood. In fact, this study aims to improve the understanding of violence emergence in psychiatric population’s criminal career by exploring the interaction of substance abuse disorder. The data collected in this study come from self-narrative stories of 9 participants who frequent a forensic psychiatry structure. These data intend to explore the criminal career of people with severe mental illness, deepen the meaning of their actions, understand the involvement of substance use in this dynamic by ascertain the interactional elements’ sequence and find which dimensions are more likely to produce violent acts. Like many before, the first contribution of this research project is, to establish a link between violent criminal actions and substance use in psychiatric population. Secondly, it appears that the outbreak of criminal behavior goes farther than this interaction between substance uses and severe mental illness. Indeed, the method used in this project allowed us to identified risk factors and clinical, contextual, historical, and relational facilitators leading to violent crimes. Third, the qualitative approach, less used in this research field, enable to support and qualify the typological model of Hodgins et al. (1989), presenting the life course of criminals with severe mental disorders. In the end, this study helps guide the development of intervention programs, for reintegration, into forensic psychiatry structure.

<p>Allosteric modulators are emerging as a new class of therapeutics for the treatment of complex disorders, including psychiatric illnesses such as schizophrenia. The disease is marked by hyperdopaminergic signaling in the striatum, which plays a role in the development of positive symptoms like delusions, hallucinations, and paranoia. Conventional antipsychotic drug therapy typically employs dopamine D2 receptor antagonists that compete with endogenous dopamine at the orthosteric, or dopamine-binding site, in an attempt to normalize these psychotic symptoms. However, they are often associated with adverse motor and metabolic side effects. Furthermore, only some antipsychotic drugs are able to treat the negative symptoms of schizophrenia, which include social withdrawal and anhedonia, and there is currently no treatment for the cognitive impairment associated with the disease.</p> <p>Allosteric modulators are safer alternatives to conventional orthosteric therapeutics as they interact with their receptor at a novel binding site and their mechanism involves modulation of endogenous signaling. Therefore, levels of endogenous ligand limit the activity of an allosteric modulator. Our lab has synthesized and evaluated over 185 compounds for their activity at the dopamine D2 receptor. Of these compounds, PAOPA is the most potent allosteric modulator, and has been shown to be effective in treating the MK-801 induced preclinical animal model of schizophrenia without causing the adverse effects induced by currently prescribed antipsychotic drugs. The objective of this study was to evaluate PAOPA’s ability to treat behavioural abnormalities in an amphetamine-sensitized model of schizophrenia.</p> <p>Four groups (n=10/group) of male Sprague Dawley rats received intraperitoneal injections three days per week on alternate days over three weeks. Group A received saline, group B received D-amphetamine (1mg/kg during week one, 2mg/kg during week two, 3mg/kg during week three), group C received PAOPA (1mg/kg), and group D received the same doses of amphetamine as group B with PAOPA (1mg/kg). Following a three-week withdrawal, each group was tested for prepulse inhibition, social interaction, and locomotor activity. Amphetamine-sensitized rats were subjected to the same tests following PAOPA administration (1mg/kg). To assess whether behavioural changes were associated with changes in brain chemistry, post-mortem dopamine levels were measured in the striatum, nucleus accumbens, and medial prefrontal cortex. Data were analyzed by one-way ANOVA or paired t test where appropriate.</p> <p>Amphetamine sensitization induced schizophrenic-like behavioural abnormalities, including deficits in prepulse inhibition and social interaction, as well as increased locomotor activity and sensitivity to amphetamine challenge. Concurrent amphetamine and PAOPA treatment prevented all amphetamine- induced behavioural abnormalities. Furthermore, amphetamine-induced deficits in prepulse inhibition and social interaction were reversed one hour following PAOPA treatment. PAOPA treatment alone had no effect on behaviour or post-mortem striatal dopamine. Behavioural changes in amphetamine-sensitized rats were accompanied by a reduction in post-mortem striatal dopamine levels. In correlation with behavioural results, PAOPA administration during amphetamine sensitization prevented this biochemical change.</p> <p>These results demonstrate that PAOPA can prevent and reverse behavioural and associated biochemical abnormalities in amphetamine-sensitized rats. PAOPA is a candidate for the development of treatments for schizophrenia.</p> / Master of Science (MSc)

<p>This thesis presents research investigating structural neural correlates of major depressive disorder (MDD). Although there are clear clinical differences between early- and late-onset MDD, they are still subject to the same diagnostic criteria and treatment strategy. Whether these differences translate into differences in cortical structure was examined in this study. By directly comparing early-onset (EOD) and late-onset (LOD) patients, we test whether age-of-onset results in changes in the extent or spatial pattern of cortical thinning.</p> <p>Chapter 1 provides a general background on the cerebral cortex, followed with a focus on cortical thickness. Chapter 2 presents a comprehensive review of the clinical and neurobiological literature on major depressive disorder as it pertains to age-of-onset. Three working hypotheses regarding the differences between early- and late-onset depression are presented and discussed.</p> <p>The results presented in this thesis show that there are both differences and similarities in cortical thickness between patients with EOD and LOD, with differences reflecting spatial extent, region-specificity, and magnitude of thickness differences. We confirmed the hypothesis of greater thinning in the dorsal lateral prefrontal cortex in depressed patients compared to healthy controls. We also correlated cortical thickness with clinical variables, which resulted in the finding of a positive correlation in the posterior cingulate cortex with illness severity.</p> <p>Few studies have used age-of-onset as a factor, which may account for some of the heterogeneity and inconsistent results seen in studies of MDD. We found that depression onset in early life is associated with greater disturbances in cortical thickness than LOD, possibly reflecting atypical development. These results provide novel insights into vulnerability and how development of depression is differentially affected by age.</p> / Master of Science (MSc)

Le très faible pourcentage d’enfants d’âge préscolaire atteints de troubles mentaux qui accèdent à des services de santé mentale spécialisés est un problème majeur de santé publique, compte tenu notamment de la prévalence élevée et des répercussions négatives importantes des troubles mentaux chez les jeunes enfants. C’est particulièrement le cas pour le trouble développemental du langage (TDL) qui est associé à des difficultés d’apprentissage et psychosociales significatives pouvant perdurer jusqu’à l’âge adulte. La présente thèse s’intéresse aux composantes de la surveillance développementale pour soutenir la détection précoce du TDL à la petite enfance en contexte pédopsychiatrique. Son objectif est de mieux cibler les facteurs de risque et les inquiétudes rapportées par les parents qui distinguent le TDL des autres troubles mentaux au sein d’un échantillon d’enfant d’âge préscolaire consultant en pédopsychiatrie. Le premier article vise à étudier les facteurs de risques propres au TDL, en les comparant aux autres troubles mentaux. L'acquisition des premières phrases après 24 mois, l’immigration maternelle et les antécédents familiaux de retard langagier ont été identifiés comme les prédicteurs les plus importants du TDL. De plus, les résultats montrent que les enfants atteints de TDL étaient exposés à un nombre significativement plus élevé de facteurs de risque que ceux atteints d'autres troubles mentaux. Le deuxième article explore la précision des inquiétudes parentales selon ses niveaux de sensibilité et spécificité ainsi que par sa valeur prédictive quant au diagnostic final des enfants. Les résultats ont démontré que les troubles du langage étaient mieux détectés par les parents que les autres troubles, tout en étant moins spécifiques, car ils pouvaient être associés à d'autres diagnostics que le TDL. Les inquiétudes parentales se sont avérées généralement fiables et pertinentes dans la détection de troubles mentaux dès l’âge préscolaire, à l’exception de la sphère motrice, au sein de laquelle les difficultés des enfants étaient sous-détectées. L’intégration des résultats des deux articles de la présente thèse montre qu’une meilleure connaissance et une utilisation plus efficiente des inquiétudes parentales ainsi que de facteurs de risque spécifiques lors des premiers stades du développement de l’enfant pourraient être déterminantes pour le pronostic du TDL, en se concentrant plus rapidement sur les interventions nécessaires et en s’assurant de la correspondance entre les besoins des familles et les services offerts. / The low percentage of preschool children with mental disorders accessing specialized mental health services is a major public health concern, given the high prevalence and significant negative impact of mental disorders in young children. This is particularly the case for developmental language disorder (DLD), which is associated with significant learning and psychosocial difficulties that can last into adulthood. This thesis focuses on the components of developmental surveillance to support the early detection of DLD in early childhood in a child psychiatric context. Its objective is to better target the risk factors and concerns reported by parents that distinguish DLD from other mental disorders in a sample of preschoolers consulting in child psychiatry. The first article aimed to study the risk factors specific to DLD, by comparing them to other mental disorders. Acquisition of first sentences after 24 months, maternal immigration and family history of language delay were identified as the most important predictors of DLD. In addition, the results demonstrate that children with DLD were exposed to a significantly higher number of risk factors than those with other mental disorders. In the second article the levels of sensitivity and specificity of parental concerns were reported, as well as its predictive value for the final diagnosis of children. The results showed that language disorders were better detected by parents than other disorders, while being less specific, as they could be associated with other diagnoses than DLD. Parental concerns have proven to be generally reliable and relevant in the detection of mental disorders from preschool age, except for the motor sphere, in which children's difficulties were under-detected. The integration of the results of our two articles demonstrates that a better knowledge and more efficient use of parental concerns as well as specific risk factors during the early stages of child development could be decisive for DLD prognosis, by focusing more quickly on the necessary interventions and ensuring the correspondence between the needs of families and the services offered.

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. / The objective of this thesis was to evaluate Espace de Transition (ET), an innovative art-based program aimed at fostering the rehabilitation of adolescents and young adults with recently stabilized psychiatric disorders and diminishing the stigmatization experienced by individuals with mental health problems. This program was designed by a team of clinicians from Ste-Justine Hospital’s psychiatry unit, in collaboration with professional artists. It is delivered since the spring of 2009. The evaluation of program ET was conducted in an independent yet collaborative manner, using a naturalistic approach and mixed methods. Data were collected before, during, and after the program from all participants who took part in two distinct sessions (N = 24), as well as from the two artist instructors, the psychoeducator who provided clinical support during the workshops, and the clinicians who referred participants (N=11). Individual and group semi-structured interviews, direct observations, and questionnaires served to collect the necessary data. Quantitative analyses of variance and qualitative thematic analyses were conducted and their results were interpreted in an integrated manner. The first empirical chapter of the thesis reports on the evaluation of the implementation of program ET. This evaluation showed that the program reached participants closely corresponding to its targeted population and that these youths globally presented elevated levels of assiduity, engagement in, and appreciation of the program. This evaluation also allowed to conclude that most essential program components were delivered as intended by designers and were largely appreciated and judged pertinent by participants and other respondents. The second empirical chapter presents an article detailing the evaluation of the effects of the program ET. This evaluation focused on three of its intermediate objectives: the improvement of 1) global functioning, 2) social comfort and competence, and 3) self-perception in program participants suffering from mental disorders. Results of this study revealed significant and positive changes in the global functioning of participants following the program, as assessed by their referring clinicians and partially corroborated by participants themselves. Improvements in social comfort and competence and self-perception were also noted in a substantial proportion of participants, although they did not translate in significant differences detected by group-level quantitative analyses. The third and last empirical chapter of the thesis reports on a study which sought to explore the mechanisms underlying the effects of program ET and to inductively elaborate a theory of action of the program. This qualitative investigation revealed four categories of mechanisms: 1) social experience and gratification, 2) desensitization by gradual exposure, 3) success and valorization, and 4) normalization. This study also allowed to identify program characteristics and components that seemed to favor the onset or impact of these mechanisms, such as the non-clinical setting and conducting of the program, the heterogeneous composition of the groups, the use of performing arts, and the pursuit of a collectively achieved artistic product and its presentation to an external public. Globally, the studies presented in the thesis support the relevance and promising character of program ET, while suggesting potential improvements for future versions. By extension, the thesis supports the potential efficacy of rehabilitation strategies which include components analogous to those of ET in fostering the recovery of youths with mental disorders.