Introduction : les programmes d’intervention précoce en premiers épisodes psychotiques (PIPÉP) constituent un modèle qui améliore l’évolution des individus souffrant de psychose débutante. Au Québec, après 30 ans de développement mené par les cliniciens, le ministère de la Santé et des Services sociaux a annoncé des mesures structurantes pour soutenir l’implantation de PIPÉP à travers la province en 2017. Objectifs : 1) Décrire le degré d’implantation des PIPÉP au Québec et leur profil d’adhésion aux composantes essentielles du modèle en 2020. 2) Décrire les différences entre les PIPÉP implantés avant et après 2017. Méthode : étude descriptive longitudinale de l’évolution des PIPÉP au Québec menée par sondage électronique en 2016 et en 2020. Résultats : - En 2020, 28 des 33 PIPÉP existants ont répondu au sondage, dont 11 implantés après 2017. - En 2016, 17 des 18 PIPÉP existants ont répondu. Des critères d’admission inclusifs, des cibles de délais maximaux et processus directs de référence favorisent l’accessibilité aux PIPÉP. Des interventions biopsychosociales variées démontrées efficaces (p. ex. : interventions familiales) sont offertes par des équipes interdisciplinaires. Le respect des ratios de patients: case manager, la collecte de données clinico-administratives et l’emploi d’outils de mesures cliniques standardisés demeurent des défis. Des différences ont été relevées entre les programmes fondés avant et après 2017, notamment en regard de la diversité d’interventions psychosociales offertes et de l’adhésion aux standards d’accessibilité. Conclusion : l’implantation rapide de PIPÉP fidèles au modèle est possible en présence de soutien gouvernemental et de la détermination des professionnels qui y œuvrent. Les PIPÉP québécois offrent des services de qualité, mais des lacunes existent en regard des composantes organisationnelles. / Introduction: Early intervention for psychosis is a service delivery model that has been shown to improve outcomes for first-episode psychosis. This model is premised on adherence to essential components. In Quebec, after 30 years of clinician-led development, the Ministry of Health and Social Services announced several measures to support the implementation of early intervention services for psychosis (EIS) across the province in 2017. Objectives: 1) To describe the state of implementation of EIS in Quebec in 2020 and their adherence to essential components of the EIS model. 2) To describe differences between programs implemented before and after 2017. Methods: A descriptive longitudinal study on EIS implementation in Quebec, involving two online surveys conducted in 2016 and 2020. Results: In 2020, 28 of the 33 existing EIS responded to the survey, including 11 which were implemented after 2017. In 2016, 17 of the 18 EIS in operation had completed the survey. Inclusive admission criteria, maximum delay targets, and open referral policies are being followed to promote easy and rapid access to EIS. A variety of effective biopsychosocial interventions (e.g., family interventions) are offered by interdisciplinary teams. Reported challenges include difficulty maintaining patient-to-case manager ratios and use of clinical/administrative databases and standardised clinical tools. There were some differences between programs founded before and after 2017, notably regarding the diversity of psychosocial interventions that are offered and adherence to accessibility standards. Conclusion: Rapid implementation of EIS that adequately adhere to the model’s essential components is possible, with increased government support and determined clinicians. EIS in Quebec provide quality services to patients, but there are shortcomings with respect to administrative and organisational components.

Introduction : Chaque année, 703 000 personnes décèdent par suicide à travers le monde et une proportion encore plus importante de personnes pensent au suicide ou font une tentative de suicide. L’étude des facteurs associés aux idées et aux comportements suicidaires vise à améliorer notre compréhension de cette problématique pour mieux cibler les personnes à risque, mieux les soutenir et, ultimement, diminuer les taux de décès par suicide. Les troubles psychotiques sont associés à une vulnérabilité accrue au suicide, particulièrement dans les premières années suivant l’émergence de la psychose, c’est-à-dire lors du premier épisode psychotique (PEP). L’objectif général de la thèse est de mieux comprendre l’évolution des idées suicidaires et des comportements suicidaires ainsi que les facteurs qui y sont associés chez les personnes présentant un PEP. Méthode : Trois études ont été réalisées. La première est une recension systématique des écrits réalisée en accord avec les critères PRISMA. Les études longitudinales portant sur la prévalence et les facteurs associés aux idées et aux comportements suicidaires chez les personnes présentant un PEP ont été répertoriées à partir de cinq banques de données et des références bibliographiques des articles pertinents. Le tri des articles, l’extraction des données ainsi que l’évaluation de la qualité des articles ont été réalisés par deux codeurs indépendants. La deuxième étude a identifié les trajectoires des idées suicidaires sur une période de cinq ans et la distribution des tentatives de suicide à travers ces trajectoires chez les patients présentant un PEP, admis entre 2005 et 2013, dans deux services d’intervention précoce pour la psychose à Montréal, Québec. Les données sur les idées suicidaires, les tentatives de suicide, les décès par suicide, et les facteurs potentiellement associés ont été évalués annuellement pendant cinq ans par des entrevues de recherche, la révision des dossiers médicaux et les rapports du coroner. Des analyses de trajectoires latentes ont été réalisées. Enfin, le troisième article a comparé l’évolution des idées et des comportements suicidaires dans des services d’intervention précoce pour la psychose, structurés de façon similaire, dans deux contextes socioculturels différents, soit à Montréal, au Canada et à Chennai, en Inde. Les données sur les idées et les comportements suicidaires ainsi que sur les facteurs potentiellement associés ont été colligées à sept temps de mesure sur une période de deux ans par des entrevues de recherche, des questionnaires standardisés ainsi qu’une révision des dossiers médicaux. Pour chacun des sites, les facteurs associés à la présence et à la sévérité des idées et des comportements suicidaires ont été comparés à l’admission avec un modèle en deux parties de type « hurdle » (modèle linéaire généralisé pour une distribution binomiale et un second modèle de régression logistique pour variable ordinale). L’évolution des idées et des comportements suicidaires a été comparée entre les sites avec un modèle à effets mixtes pour réponse ordinale. Résultats : La recension des écrits comprend 17 articles, réalisés dans des pays à haut revenu, et révèle que près du tiers des patients présentant un PEP rapporte avoir eu des idées suicidaires et fait une tentative de suicide avant leur admission dans les services d’intervention précoce pour la psychose. En général, une diminution des idées suicidaires et des comportements suicidaires a été observée pendant le suivi. Les symptômes dépressifs ainsi les antécédents d’idées et de comportements suicidaires ont été associés à un plus grand risque de comportements suicidaires. Les services d’intervention précoce pour la psychose ont plutôt été associés à un moindre risque de décès par suicide. La deuxième étude, incluant 382 patients, a démontré l’hétérogénéité de l’évolution des idées suicidaires chez les personnes présentant un PEP en identifiant trois trajectoires distinctes : Une première trajectoire caractérisée par un risque faible et décroissant de présenter des idées suicidaires (85.1%), une seconde marquée par un déclin précoce des idées suicidaires suivi d’une augmentation en fin de suivi à la clinique PEP (7.8%), ainsi qu’une troisième trajectoire caractérisée par une persistance des idées suicidaires au cours des cinq années de suivi (7.1%). Alors que les antécédents d’idées suicidaires et le trouble d’usage de cocaïne ont été associés à la seconde trajectoire, les antécédents d’idées suicidaires et de tentatives de suicide ainsi que le trouble d’usage d’alcool ont été associés à la troisième trajectoire. La troisième étude, incluant 333 patients (165 à Montréal, 168 à Chennai), a révélé une diminution des idées et des comportements suicidaires dans les deux sites au cours du suivi, avec toutefois un risque suicidaire plus élevé tout au long du suivi pour les patients suivis à Montréal. Certains facteurs ont été associés à un plus grand risque d’idées et de comportements suicidaires dans les deux contextes (comme la dépression et les antécédents de tentatives de suicide) alors que certains facteurs étaient plutôt spécifiques au contexte (comme le statut relationnel et le genre). Conclusion : Les trois manuscrits soutiennent que la prévalence des idées suicidaires et des comportements suicidaires est élevée chez les personnes présentant un PEP, quel que soit le milieu ou le contexte socioculturel. Les résultats plaident en faveur de la détection précoce de la psychose afin d’évaluer le risque suicidaire et intervenir rapidement auprès des personnes vivant un PEP puisque les taux d’idées et de comportements suicidaires sont particulièrement élevés avant l’entrée dans les services et au début du suivi. Une évaluation continue du risque suicidaire est nécessaire jusqu’à la toute fin du suivi pour soutenir les différents sous-groupes de patients, dont ceux plus à risque de présenter des idées suicidaires croissantes ou persistantes. Les personnes présentant des symptômes dépressifs, des antécédents d’idées et de tentatives de suicide ainsi qu’un trouble de l’usage de substances devraient être ciblées pour bénéficier d’interventions visant à prévenir le suicide, et ce, dès le début du suivi. Enfin, la thèse a permis de mieux comprendre l’évolution des idées et des comportements suicidaires chez les personnes présentant un PEP et d’identifier différentes avenues de recherches futures. / Introduction: Every year, 703,000 persons die by suicide worldwide and an even greater proportion of people think of or attempt suicide. Studying factors associated with suicidal thoughts and behaviours aims to improve our understanding of this issue to better target and support those at risk and ultimately decrease rates of suicide deaths. Psychotic disorders are associated with an increased vulnerability to suicide, particularly in the first years following psychosis onset, i.e., during first-episode psychosis (FEP). The overall goal of the dissertation is to better understand the course of suicidal thoughts and behaviours and the factors associated therewith in persons with FEP. Method: Three studies were conducted. The first was a systematic review in compliance with PRISMA guidelines. Longitudinal studies on the prevalence of and factors associated with suicidal thoughts and behaviours in FEP were identified from five databases and reference lists of relevant articles. Screening, data extraction, and quality assessment of selected studies were performed by two independent reviewers. The second study identified trajectories of suicidal ideation over a five-year period and the distribution of suicide attempts across these trajectories in patients with FEP admitted between 2005 and 2013 to two early intervention services for psychosis in Montreal, Quebec. Data on suicidal ideation, suicide attempts, suicide deaths, and potentially associated factors were assessed annually for five years through research interviews, medical records review, and coroners' reports. Latent trajectory analyses were performed. Finally, the third study compared the course of suicidal thoughts and behaviours in similarly structured early intervention services for psychosis in two different sociocultural contexts, Montreal, Canada and Chennai, India. Data on suicidal thoughts and behaviours and potentially associated factors were collected at seven time points over two years through research interviews, standardized questionnaires, and medical records review. For each site, factors associated with presence and severity of suicidal thoughts and behaviours were compared at admission with a two-part hurdle model (generalized linear model for a binomial distribution and a second ordered logistic regression model). Course of suicidal thoughts and behaviours was compared between sites with a mixed-effects ordered logistic regression. Results: The systematic review included 17 articles from high-income countries and found that nearly one third of patients with FEP reported suicidal ideation and attempts prior to admission to early intervention services for psychosis. In general, a decrease in suicidal thoughts and behaviours was observed during follow-up. Depressive symptoms and a history of suicidal thoughts and behaviours were associated with a greater risk of suicidal behaviours. Early intervention services for psychosis were rather associated with a lower risk of death by suicide. The second study, including 382 patients, showed heterogeneity in the evolution of suicidal ideation in persons with FEP by identifying three distinct trajectories: a first trajectory characterized by a low and decreasing risk of presenting suicidal ideation (85.1%), a second trajectory marked by an early decline in suicidal ideation followed by an increase at the end of follow-up (7.8%), and a third trajectory characterized by persistence of suicidal ideation during the five-year follow-up (7.1%) While history of suicidal ideation and cocaine use disorder were associated with the second trajectory, history of suicidal ideation and suicide attempts, and alcohol use disorder were associated with the third trajectory. The third study, including 333 patients (165 in Montreal, 168 in Chennai), found a decrease in suicidal thoughts and behaviours over follow-up in both sites, although the risk was higher throughout follow-up for Montreal patients. Some factors were associated with a higher risk of suicidal thoughts and behaviours across contexts (e.g., depression and history of suicide attempts), while some factors were rather context-specific (e.g., relationship status and gender). Conclusion: The three manuscripts support that the prevalence of suicidal thoughts and behaviours is high among persons with FEP, regardless of sociocultural context or setting. The results argue for early detection of psychosis to assess suicidal risk and intervene promptly with individuals with FEP, as rates of suicidal thoughts and behaviours are particularly high prior to service entry and at the beginning of follow-up. Ongoing assessment of suicidal risk is needed until the very end of follow-up to support different subgroups of patients, including those at higher risk of developing increasing or persistent suicidal ideation. Individuals with depressive symptoms, a history of suicide ideation and attempts, and a substance use disorder should be targeted for suicide-focused interventions early in follow-up. Finally, the dissertation provided a better understanding of the course of suicidal thoughts and behaviours in persons with FEP and allowed for the identification of different areas for future research.

La schizophrénie est un trouble mental qui touche environ un pour cent de la population et dont les symptômes et troubles associés affectent la capacité des individus à fonctionner dans la communauté. Dans la dernière décennie, des services spécialisés dans la détection et l’intervention précoce dès le premier épisode psychotique ont été implantés dans plusieurs pays. Or, ces services ont surtout ciblé, jusqu’ici, la réduction des symptômes et de la demande de soins. Les difficultés fonctionnelles des jeunes adultes schizophrènes justifient que les services qui leur sont destinés misent également sur la réadaptation et l’amélioration du fonctionnement dans la communauté. Les besoins, priorités et préférences de cette population, ainsi que l’impact des particularités développementales du jeune âge adulte sur leur fonctionnement, sont méconnus. Cette étude propose de documenter le fonctionnement dans la communauté des jeunes adultes schizophrènes au stade du premier épisode psychotique et de le comparer à celui de leurs pairs sans psychopathologie. L’utilisation d’un modèle théorique de réadaptation, le modèle de Compétence, permet de conceptualiser le fonctionnement sous l’angle de la relation personne-environnement. Ce projet s’inscrit dans une approche de recherche synthétique ; le devis préconisé est une étude de cas multiples avec l’utilisation de méthodes mixtes (qualitatives et quantitatives), selon un modèle concurrent de triangulation (Creswell & Plano Clark, 2007). Les résultats mettent en lumière des différences entre les deux groupes dans les domaines des relations sociales et conjugales, du cheminement académique et de l’indépendance résidentielle et financière. Les données qualitatives, analysées selon le modèle de la théorisation ancrée (Glaser & Strauss, 1967), permettent de comprendre les processus sociaux impliqués dans l’accomplissement des tâches développementales au jeune âge adulte, ainsi que les conditions personnelles et systémiques sous-jacentes. Les résultats soulignent l’importance d’adapter les services résidentiels aux particularités développementales, de favoriser le soutien aux études et d’inclure les amis et les pairs dans la réadaptation des personnes touchées. Cette thèse permet à la fois d’identifier les besoins et priorités de cette population, de donner une voix aux jeunes adultes schizophrènes dans l’élaboration des services qui leur sont destinés et d’examiner les enjeux méthodologiques reliés à l’utilisation d’un devis mixte en recherche clinique. / Schizophrenia is a mental health disease that affects approximately one percent of the population and whose symptoms and associated deficits hinder community functioning in affected individuals. Over the last decade, specialized services in early detection and intervention of first-episode psychosis have been implemented in many countries. So far, these services have primarily targeted symptoms and use of psychiatric care as outcomes. The significant functional difficulties experienced by young adults with schizophrenia call for a shift in emphasis towards rehabilitative strategies. No study has documented the needs, preferences and priorities of this population in terms of rehabilitation services and of the influence of developmental characteristics of young adulthood on functional outcome. This study aims to examine community functioning of young adults with schizophrenia after the first episode of psychosis and to compare it with community functioning of their unaffected peers. Community functioning is conceptualized from the perspective of person-environment interaction through the lens of the Model of Competence. A multiple case study is used within the canvas of a synthetic research approach. A concurrent, mixed methods design (qualitative and quantitative) is implemented for triangulation purposes (Creswell & Plano Clark, 2007). Results indicate salient differences between the clinical and comparison groups in the areas of social and conjugal relationships, academic achievement as well as financial and residential independence. Qualitative data analyzed through a grounded theory approach (Glaser & Strauss, 1967) highlight the social processes through which young adults achieve developmental tasks. Personal and systemic conditions that constraint and facilitate processes are recognized. The results have implications for psychiatric practices. First, residential services should be adapted to the developmental characteristics of this age group. Second, supported education should be valued and implemented as a key service for young adults with schizophrenia. Third, friends and members of the social network should be included as early and intensively as possible in the rehabilitation process. Overall, this study leads to methodological innovations in the use of mixed methods in clinical research, to identification of needs and priorities in the design of rehabilitation strategies and to the recognition of the voices and input of young adults with schizophrenia.

No description available.

INTRODUÇÃO: Os transtornos mentais psicóticos são condições frequentes na população geral e estão associados a grande morbidade e disfuncionalidade. Apesar disso, as bases fisiopatológicas destes transtornos ainda estão em investigação. Estudos neuropatológicos post-mortem e de neuroimagem in vivo sugerem haver comprometimento da microestrutura de substância branca (SB) cerebral nestas condições clínicas, associado a alterações da conectividade cerebral. No entanto, nenhuma investigação prévia de neuroimagem avaliou especificamente se tais anormalidades microestruturais podem ser dependentes do estado clínico do paciente, i.e., se tais alterações podem variar de acordo com a fase da doença. Outra linha de investigação biológica em psicoses aponta para alterações na atividade da fosfolipase A2 (PLA2), uma enzima essencial a diversas funções na homeostase cerebral, incluindo manutenção de membrana celular, mielinização e atividade inflamatória. Estudos prévios sugerem haver relação entre alterações na atividade desta enzima e as fases da esquizofrenia. Entretanto, não há estudos translacionais que tenham avaliado como tais alterações se relacionam com anormalidades microestruturais de SB em pacientes psicóticos. OBJETIVOS: Investigar a hipótese de que alterações de microestrutura de SB presentes em pacientes em fase aguda do primeiro episódio psicótico (PEP) sejam potencialmente reversíveis após estabilização clínica; investigar também possíveis alterações estado-dependentes da atividade de PLA2 no PEP; e examinar interações entre manifestações clínicas, microestrutura de SB cerebral e atividade de PLA2 na fisiopatologia do PEP. METODOLOGIA: Pacientes em PEP não afetivo foram avaliados em dois períodos no tempo: durante a fase aguda da doença (T0); após remissão estável de sintomas (T1). Um grupo controle de voluntários saudáveis (CS) também foi avaliado longitudinalmente. Para investigar alterações de microestrutura de SB estado-dependentes, análises voxel-a-voxel de mapas cerebrais de índices de anisotropia (fractional anisotropy, FA) e difusividade (trace, TR) foram conduzidas, assim como o cálculo de correlações entre tais índices de DTI, variáveis clínicas e atividade de PLA2. A atividade dos três principais subgrupos de PLA2 em plaquetas foi estimada através de um método radioenzimático. RESULTADOS: 25 pacientes PEP e 51 CS foram avaliados em T0, com coleta de dados clínico-demográficos, ressonância magnética (RM) e amostra de sangue. Destes, 21 PEP e 36 CS realizaram a segunda aquisição de RM. No baseline (T0), os pacientes PEP apresentaram redução difusa de FA (p < 0,05, FDR), afetando principalmente SB fronto-límbica e fascículos associativos, projetivos e comissurais. As análises longitudinais demonstraram que a remissão clínica se associou a aumentos de FA em tratos de SB acometidos em T0 (p < 0,001, não corrigido), além de robustas correlações inversas entre aumentos de FA e redução sintomas ao longo do tempo (p < 0,05, FDR). As análises de PLA2 não demostraram efeitos estado-dependentes ou correlações consistentes com os índices de DTI. CONCLUSÃO: Alterações da microestrutura de SB afetando tratos cerebrais essenciais para a integração de informação perceptual, cognição e emoções são detectáveis logo após o início do PEP e podem ser parcialmente revertidas em relação direta com a remissão de sintomas psicóticos agudos. Nossos achados reforçam a visão de que anormalidades de SB de tratos cerebrais são um componente neurobiológico central nos transtornos psicóticos agudos, e que a recuperação de tal patologia de SB pode levar à melhora clínica. Por outro lado, a atividade de PLA2 não parece ter associação direta com o estado de doença ou moderar as alterações microestruturais dinâmicas de SB aqui observadas. Estudos com amostras maiores e com um maior número de avaliações ao longo do tempo são necessários para confirmar e ampliar os resultados aqui apresentados / INTRODUCTION: Psychotic disorders are frequent conditions in the general population and are associated to severe morbidity and functional impairment. Notwithstanding, the pathophysiological basis of such disorders is still under investigation. Post-mortem neuropathologic investigations and in vivo neuroimaging studies have pointed to the occurrence of abnormalities in the microstructure of brain white matter (WM) in such clinical conditions, which are associated to changes in brain connectivity. However, no previous neuroimaging investigation has specifically examined whether such microstructural abnormalities would be state-dependent, i.e., whether such changes could relate to the illness phase. Another field of biological investigation in psychosis points to changes in the activity of phospholipase A2 enzyme (PLA2), which is essential to several functions implicated in brain homeostasis, such as the maintenance of cellular membrane, myelination and inflammatory activity. Previous studies suggest the existence of a relationship between changes on PLA2 activity and schizophrenia phase. Nonetheless, no translational study to date has examined the potential interplay between PLA2 activity and WM microstructural abnormalities in psychotic patients. OBJECTIVES: To investigate the hypothesis that WM microstructural changes observed in patients during the acute first-episode psychosis (FEP) are potentially reversible following clinical remission; to investigate possible state-dependent changes in PLA2 activity in FEP; and to examine interactions between clinical manifestations, brain WM microstructure and PLA2 activity in the pathophysiology of FEP. METODOLOGY: Patients with non-affective FEP were evaluated in two time points: during the acute phase (T0) and following sustained remission (T1). A control group of healthy volunteers (HC) was also longitudinally studied. In order to investigate state-dependent WM microstructure changes, voxelwise analyses of brain maps of anisotropy (fractional anisotropy, FA) and diffusivity (trace, TR) indexes were conducted, as well as correlations between such DTI metrics, clinical variables and PLA2 activity. The activity of the three main PLA2 subgroups was assessed in platelets using a radioenzymatic method. RESULTS: 25 FEP and 51 HC were evaluated at T0 (clinical and demographic data, MRI scanning, and blood collection). Out of these, 21 FEP and 36 HC also underwent a second MRI acquisition. At baseline (T0), FEP patients presented widespread reduction of FA (p < 0.05, FDR), affecting mainly fronto-limbic WM and associative, projective and commissural fasciculi. Longitudinal analyses showed that clinical remission was associated with FA increase in WM tracts that were affected at T0 (p < 0.001, uncorrected), besides robust inverse correlations between FA increase and symptoms reduction over time (p < 0.05, FDR). PLA2 analyses failed to show state-dependent effects or consistent correlations to DTI indexes. CONCLUSION: WM changes affecting brain tracts critical to the integration of perceptual information, cognition and emotions are detectable soon after the onset of FEP and may partially reverse in direct relation to the remission of acute psychotic symptoms. Our findings reinforce the view that WM abnormalities are a key neurobiological feature of acute psychotic disorders, and that recovery from such WM pathology can lead to amelioration of symptoms. In the other hand, it seems that PLA2 activity has no direct relationship to the disease state or modulatory effects on the dynamic WM changes observed herein. Studies with larger samples and with more time points evaluations are necessary to confirm and expand the findings reported herein

INTRODUÇÃO: Os transtornos mentais psicóticos são condições frequentes na população geral e estão associados a grande morbidade e disfuncionalidade. Apesar disso, as bases fisiopatológicas destes transtornos ainda estão em investigação. Estudos neuropatológicos post-mortem e de neuroimagem in vivo sugerem haver comprometimento da microestrutura de substância branca (SB) cerebral nestas condições clínicas, associado a alterações da conectividade cerebral. No entanto, nenhuma investigação prévia de neuroimagem avaliou especificamente se tais anormalidades microestruturais podem ser dependentes do estado clínico do paciente, i.e., se tais alterações podem variar de acordo com a fase da doença. Outra linha de investigação biológica em psicoses aponta para alterações na atividade da fosfolipase A2 (PLA2), uma enzima essencial a diversas funções na homeostase cerebral, incluindo manutenção de membrana celular, mielinização e atividade inflamatória. Estudos prévios sugerem haver relação entre alterações na atividade desta enzima e as fases da esquizofrenia. Entretanto, não há estudos translacionais que tenham avaliado como tais alterações se relacionam com anormalidades microestruturais de SB em pacientes psicóticos. OBJETIVOS: Investigar a hipótese de que alterações de microestrutura de SB presentes em pacientes em fase aguda do primeiro episódio psicótico (PEP) sejam potencialmente reversíveis após estabilização clínica; investigar também possíveis alterações estado-dependentes da atividade de PLA2 no PEP; e examinar interações entre manifestações clínicas, microestrutura de SB cerebral e atividade de PLA2 na fisiopatologia do PEP. METODOLOGIA: Pacientes em PEP não afetivo foram avaliados em dois períodos no tempo: durante a fase aguda da doença (T0); após remissão estável de sintomas (T1). Um grupo controle de voluntários saudáveis (CS) também foi avaliado longitudinalmente. Para investigar alterações de microestrutura de SB estado-dependentes, análises voxel-a-voxel de mapas cerebrais de índices de anisotropia (fractional anisotropy, FA) e difusividade (trace, TR) foram conduzidas, assim como o cálculo de correlações entre tais índices de DTI, variáveis clínicas e atividade de PLA2. A atividade dos três principais subgrupos de PLA2 em plaquetas foi estimada através de um método radioenzimático. RESULTADOS: 25 pacientes PEP e 51 CS foram avaliados em T0, com coleta de dados clínico-demográficos, ressonância magnética (RM) e amostra de sangue. Destes, 21 PEP e 36 CS realizaram a segunda aquisição de RM. No baseline (T0), os pacientes PEP apresentaram redução difusa de FA (p < 0,05, FDR), afetando principalmente SB fronto-límbica e fascículos associativos, projetivos e comissurais. As análises longitudinais demonstraram que a remissão clínica se associou a aumentos de FA em tratos de SB acometidos em T0 (p < 0,001, não corrigido), além de robustas correlações inversas entre aumentos de FA e redução sintomas ao longo do tempo (p < 0,05, FDR). As análises de PLA2 não demostraram efeitos estado-dependentes ou correlações consistentes com os índices de DTI. CONCLUSÃO: Alterações da microestrutura de SB afetando tratos cerebrais essenciais para a integração de informação perceptual, cognição e emoções são detectáveis logo após o início do PEP e podem ser parcialmente revertidas em relação direta com a remissão de sintomas psicóticos agudos. Nossos achados reforçam a visão de que anormalidades de SB de tratos cerebrais são um componente neurobiológico central nos transtornos psicóticos agudos, e que a recuperação de tal patologia de SB pode levar à melhora clínica. Por outro lado, a atividade de PLA2 não parece ter associação direta com o estado de doença ou moderar as alterações microestruturais dinâmicas de SB aqui observadas. Estudos com amostras maiores e com um maior número de avaliações ao longo do tempo são necessários para confirmar e ampliar os resultados aqui apresentados / INTRODUCTION: Psychotic disorders are frequent conditions in the general population and are associated to severe morbidity and functional impairment. Notwithstanding, the pathophysiological basis of such disorders is still under investigation. Post-mortem neuropathologic investigations and in vivo neuroimaging studies have pointed to the occurrence of abnormalities in the microstructure of brain white matter (WM) in such clinical conditions, which are associated to changes in brain connectivity. However, no previous neuroimaging investigation has specifically examined whether such microstructural abnormalities would be state-dependent, i.e., whether such changes could relate to the illness phase. Another field of biological investigation in psychosis points to changes in the activity of phospholipase A2 enzyme (PLA2), which is essential to several functions implicated in brain homeostasis, such as the maintenance of cellular membrane, myelination and inflammatory activity. Previous studies suggest the existence of a relationship between changes on PLA2 activity and schizophrenia phase. Nonetheless, no translational study to date has examined the potential interplay between PLA2 activity and WM microstructural abnormalities in psychotic patients. OBJECTIVES: To investigate the hypothesis that WM microstructural changes observed in patients during the acute first-episode psychosis (FEP) are potentially reversible following clinical remission; to investigate possible state-dependent changes in PLA2 activity in FEP; and to examine interactions between clinical manifestations, brain WM microstructure and PLA2 activity in the pathophysiology of FEP. METODOLOGY: Patients with non-affective FEP were evaluated in two time points: during the acute phase (T0) and following sustained remission (T1). A control group of healthy volunteers (HC) was also longitudinally studied. In order to investigate state-dependent WM microstructure changes, voxelwise analyses of brain maps of anisotropy (fractional anisotropy, FA) and diffusivity (trace, TR) indexes were conducted, as well as correlations between such DTI metrics, clinical variables and PLA2 activity. The activity of the three main PLA2 subgroups was assessed in platelets using a radioenzymatic method. RESULTS: 25 FEP and 51 HC were evaluated at T0 (clinical and demographic data, MRI scanning, and blood collection). Out of these, 21 FEP and 36 HC also underwent a second MRI acquisition. At baseline (T0), FEP patients presented widespread reduction of FA (p < 0.05, FDR), affecting mainly fronto-limbic WM and associative, projective and commissural fasciculi. Longitudinal analyses showed that clinical remission was associated with FA increase in WM tracts that were affected at T0 (p < 0.001, uncorrected), besides robust inverse correlations between FA increase and symptoms reduction over time (p < 0.05, FDR). PLA2 analyses failed to show state-dependent effects or consistent correlations to DTI indexes. CONCLUSION: WM changes affecting brain tracts critical to the integration of perceptual information, cognition and emotions are detectable soon after the onset of FEP and may partially reverse in direct relation to the remission of acute psychotic symptoms. Our findings reinforce the view that WM abnormalities are a key neurobiological feature of acute psychotic disorders, and that recovery from such WM pathology can lead to amelioration of symptoms. In the other hand, it seems that PLA2 activity has no direct relationship to the disease state or modulatory effects on the dynamic WM changes observed herein. Studies with larger samples and with more time points evaluations are necessary to confirm and expand the findings reported herein

La schizophrénie est un trouble mental qui touche environ un pour cent de la population et dont les symptômes et troubles associés affectent la capacité des individus à fonctionner dans la communauté. Dans la dernière décennie, des services spécialisés dans la détection et l’intervention précoce dès le premier épisode psychotique ont été implantés dans plusieurs pays. Or, ces services ont surtout ciblé, jusqu’ici, la réduction des symptômes et de la demande de soins. Les difficultés fonctionnelles des jeunes adultes schizophrènes justifient que les services qui leur sont destinés misent également sur la réadaptation et l’amélioration du fonctionnement dans la communauté. Les besoins, priorités et préférences de cette population, ainsi que l’impact des particularités développementales du jeune âge adulte sur leur fonctionnement, sont méconnus. Cette étude propose de documenter le fonctionnement dans la communauté des jeunes adultes schizophrènes au stade du premier épisode psychotique et de le comparer à celui de leurs pairs sans psychopathologie. L’utilisation d’un modèle théorique de réadaptation, le modèle de Compétence, permet de conceptualiser le fonctionnement sous l’angle de la relation personne-environnement. Ce projet s’inscrit dans une approche de recherche synthétique ; le devis préconisé est une étude de cas multiples avec l’utilisation de méthodes mixtes (qualitatives et quantitatives), selon un modèle concurrent de triangulation (Creswell & Plano Clark, 2007). Les résultats mettent en lumière des différences entre les deux groupes dans les domaines des relations sociales et conjugales, du cheminement académique et de l’indépendance résidentielle et financière. Les données qualitatives, analysées selon le modèle de la théorisation ancrée (Glaser & Strauss, 1967), permettent de comprendre les processus sociaux impliqués dans l’accomplissement des tâches développementales au jeune âge adulte, ainsi que les conditions personnelles et systémiques sous-jacentes. Les résultats soulignent l’importance d’adapter les services résidentiels aux particularités développementales, de favoriser le soutien aux études et d’inclure les amis et les pairs dans la réadaptation des personnes touchées. Cette thèse permet à la fois d’identifier les besoins et priorités de cette population, de donner une voix aux jeunes adultes schizophrènes dans l’élaboration des services qui leur sont destinés et d’examiner les enjeux méthodologiques reliés à l’utilisation d’un devis mixte en recherche clinique. / Schizophrenia is a mental health disease that affects approximately one percent of the population and whose symptoms and associated deficits hinder community functioning in affected individuals. Over the last decade, specialized services in early detection and intervention of first-episode psychosis have been implemented in many countries. So far, these services have primarily targeted symptoms and use of psychiatric care as outcomes. The significant functional difficulties experienced by young adults with schizophrenia call for a shift in emphasis towards rehabilitative strategies. No study has documented the needs, preferences and priorities of this population in terms of rehabilitation services and of the influence of developmental characteristics of young adulthood on functional outcome. This study aims to examine community functioning of young adults with schizophrenia after the first episode of psychosis and to compare it with community functioning of their unaffected peers. Community functioning is conceptualized from the perspective of person-environment interaction through the lens of the Model of Competence. A multiple case study is used within the canvas of a synthetic research approach. A concurrent, mixed methods design (qualitative and quantitative) is implemented for triangulation purposes (Creswell & Plano Clark, 2007). Results indicate salient differences between the clinical and comparison groups in the areas of social and conjugal relationships, academic achievement as well as financial and residential independence. Qualitative data analyzed through a grounded theory approach (Glaser & Strauss, 1967) highlight the social processes through which young adults achieve developmental tasks. Personal and systemic conditions that constraint and facilitate processes are recognized. The results have implications for psychiatric practices. First, residential services should be adapted to the developmental characteristics of this age group. Second, supported education should be valued and implemented as a key service for young adults with schizophrenia. Third, friends and members of the social network should be included as early and intensively as possible in the rehabilitation process. Overall, this study leads to methodological innovations in the use of mixed methods in clinical research, to identification of needs and priorities in the design of rehabilitation strategies and to the recognition of the voices and input of young adults with schizophrenia.

Introduction : Quoique plus de 90 minutes/semaine d’activité physique (AP) soient recommandées, peu d'individus présentant un premier épisode psychotique (PEP) en pratiquent, malgré la présence de complications métaboliques fréquentes. La littérature suggère qu'une intervention d'AP incluant leurs préférences d’AP et des conseils motivationnels faciliterait leur adhésion. Objectifs: Vérifier la faisabilité, l’acceptabilité et l’impact d’une intervention d’AP sur la motivation à l’AP, le niveau d’AP, de sédentarité et la participation sociale. Méthodes: Essai clinique ouvert (étude pilote) conduit auprès de PEP. L’intervention de 24 séances d’AP supervisées est basée sur les « préférences-patient » et inclut des conseils motivationnels utilisant le modèle transthéorique. La faisabilité et l’acceptabilité étaient mesurées grâce au taux d’abandon, de présence et à la satisfaction. La motivation à l’AP, la participation sociale, le niveau d’AP et de sédentarité ont été mesurés. Résultats: Des 40 PEP (25,63±4,22 ans, 52,5% de femmes) recrutés, 40% ont abandonné; le taux de présence était 67,5%. Les PEP (94%) étaient beaucoup (4/5) à énormément (5/5) satisfaits. Le niveau d’AP est passé de 52,71 à 91,79 minutes/semaine (recommandations atteints) et la sédentarité de 90,85 à 33,75 ± 49,16 minutes. Aucun impact observé sur la motivation d’AP et la participation sociale. Conclusion: Les résultats préliminaires suggèrent qu'une intervention basée sur les préférences-patients est faisable et acceptable chez les PEP. De futures études contrôlées randomisées permettraient de déterminer si la diminution de la sédentarité et l’augmentation d’AP sont réellement attribuables à cette intervention et si elle peut contribuer à réduire les complications métaboliques chez les PEP. / Introduction: Although 90 minutes or more/week of physical activity (PA) is recommended, few individuals with early psychosis (IEP) practice it despite the frequent presence of metabolic complications. The literature suggests that a PA intervention including their preferred PA and motivational counseling would facilitate their adherence. Objectives: To determine the feasibility, acceptability and impact of a PA intervention on PA motivation, PA level, sedentary time and social participation. Methods: Open clinical trial (pilot study) conducted with IEP. The PA intervention of 24 supervised PA sessions is based on “patients-preferences” and includes motivational counseling using the transtheoretical model. Feasibility and acceptability were measured by drop-out rates and attendance and satisfaction level. PA motivation, PA level, level of physical inactivity and social participation were measured pre and post intervention. Results: Of the 40 IEP (age: 25.63 ± 4.22 years, 52.5% of women) recruited, 40% dropped out and the attendance rate was 67.5%. The satisfaction was rated (94%) “very satisfied” to “very much”. The PA level increased from 52,71 to 91.79 minutes/week (reaching recommendations) and physical inactivity decreased from 90,85 to 33.75 ± 49.16 minutes. The intervention had no impact on PA motivation and social participation. Conclusion: Our preliminary results suggest that an intervention based on patient preferences is feasible and acceptable in IEP. Future randomised controlled trials would allow to determine if the decreased physical inactivity and increased PA levels are due to this intervention and if it may contribute to reduce the frequent metabolic complications in IEP.