Quetiapine modulates anxiety-like behaviours and alleviates the decrease of BDNF in the amygdala of an APP/PS1 transgenic mouse model of Alzheimer’s disease

Quetiapine, an atypical antipsychotic drug, is effective in treating the behavioural and the psychological symptoms of dementia (BPSD). The objective of this study was to examine the effects of quetiapine on anxiety-like behaviour in the amyloid precursor protein (APP)/ presenilin 1 (PS1) double transgenic mouse model of Alzheimer’s disease (AD). The mice were treated with quetiapine (0, 2.5, or 5 mg/kg/day) orally in drinking water for 7 or 10 months starting from 2 months of age. Conditioned anxiety was measured using the elevated T-maze (ETM). To measure memory, the Y-maze and the Morris Water maze were employed. After behavioural testing, â-amyloid (Aâ) plaques in the hippocampus and cortex of transgenic mice were stained using Congo Red. Brain-derived neurotrophic factor (BDNF) in the basolateral amygdala (BLA) and the hippocampus of mice was examined using immunohistochemical methods. The statistics revealed an interaction between quetiapine and APP/PS1 double transgenic mice in the avoidance phase of the ETM. Quetiapine modulates anxiety-like behaviours in the ETM. The anxiety-like behaviours were associated with reductions in BDNF levels in the BLA and hippocampus of the transgenic mice. This was reversed by treatment with quetiapine. Furthermore, chronic administration of quetiapine attenuated the memory impairment and decreased the Aâ plaque load in the brain. This study demonstrates that quetiapine normalizes anxiety-like behaviour and up-regulates cerebral BDNF levels in the APP/PS1 mice, suggesting that quetiapine may function as a neuroprotectant as well as an antipsychotic in treating the BPSD associated with AD

Une validation québécoise du Satisfaction with Life Domains Scale

La version québécoise de l'Échelle de satisfaction avec les domaines de la vie (ESDV), développée aux Etats-Unis auprès de la population générale et adaptée pour des personnes avec des problèmes sévères et persistants de santé mentale a été validée auprèsI d'un échantillon de 266 personnes de la population générale, et de 245 personnes avec des troubles mentaux sévères. Les analyses factorielles ont permis d'identifier quatre sous-échelles dans la population clinique et cinq dans la population générale. La consistance interne de l'échelle globale (alpha = 0,90) et des sous-échelles (alpha entre 0,60 et 0,84) s'est avérée excellente et la stabilité temporelle de l'instrument s'est avérée bonne (r = 0,73). De plus, des analyses de la variance et l'analyse discriminante permettent de constater que les sous-échelles ont un pouvoir discriminant élevé ; elles permettent de distinguer la population générale, les bénéficiaires d'aide sociale et les personnes psychotiques. Les résultats obtenus suggèrent que l'ESDV possède de très bonnes qualités psychométriques et constitue une mesure valide de qualité de vie subjective pour desI études descriptives ou évaluatives.This article presents the results of the Quebec validation of the Sa-tisfaction With Life Domains Scale. This scale was développée in theUnited States for the general population and adapted for severely men-tally ill individuals. Two hundred and sixty six individuals from the ge-neral population and 245 severely mentally ill persons participated inthis study. Factor anlysis allowed the identification of four sub-scalesfor the clinical population and five for the general population. The scale(alpha=0,90) and the sub-scales (alpha between 0,60 et 0,84) show ex-cellent internal consistencies and the test-retest reliability was good (r=0,73). Moreover, analysis of the variance and the discriminant analysisallow to acknowledge that the sub-scales have a high discriminatingpower; they allow to distinguish the general population from welfare re-cipient and people suffering from psychosis. The overall results suggestthat l'Échelle de satisfaction des domaines de vie have good psychome-tric properties and can be considered as a valid instrument for assessingsubjective quality of life in descriptive or evaluative studies

Différences et similitudes dans la perception de la schizophrénie entre les omnipraticiens et la population générale québécoise

Le rôle potentiel des omnipraticiens à l’égard d’une maladie comme la schizophrénie a été redéfinie lors du dernier Plan d’organisation de la santé mentale au Québec en 2006. Dans cet article les auteurs présentent des résultats concernant la perception et les attitudes des omnipraticiens du Québec vis-à-vis des patients souffrant de cette affection. Les résultats obtenus à travers un sondage sont comparés à ceux obtenus grâce à 5 questions communes posées à la population québécoise en général. Un court questionnaire, composé de 5 items choisis à partir d’un questionnaire plus élargi et présenté à la population générale, a été proposé aux omnipraticiens du Québec. Ces items sondaient la perception et l’attitude des médecins à l’égard de la schizophrénie. À partir d’un échantillon aléatoire de 3 500 omnipraticiens, un taux de 29 %, soit un peu plus de mille (1003, 46 % de femmes et 54 % d’hommes), répondants a été observé. Les auteurs ont constaté des différences significatives entre les omnipraticiens et la population québécoise générale dans la tendance à vouloir offrir de l’aide aux personnes souffrant de schizophrénie (omnipraticiens = 58 % versus population générale : 45 %). Également, un plus haut pourcentage d’omnipraticiens (72 %) a dit ressentir de la compassion envers les patients souffrant de schizophrénie versus 27 % dans la population en général. Les omnipraticiens ont dit se sentir moins à l’aise de discuter ouvertement de la maladie à un membre de la famille si ce dernier était affligé de la schizophrénie (26 % versus 48 %). Il n’y avait pas de différence entre les deux populations en ce qui concerne le jugement de la sévérité de la schizophrénie dans le champ des maladies y compris des maladies mentales.This paper presents results concerning the perceptions and attitudes of Quebec physicians towards patients with schizophrenia and compares data obtained from a previous poll to data drawn from answers of five common questions asked to the general population. A short questionnaire with 5 items selected earlier from a broader questionnaire submitted to the general population, has been distributed to Quebec physicians. These items inquired about the perceptions and attitudes of physicians towards schizophrenia. A randomized sample of physicians was performed. Three thousand and five hundred (3 500) physicians were selected and distributed questionnaires. A response rate of 29 %, a little more than one thousand (1003 responses) was observed, 46 % women and 54 % men. The authors have found significant differences between physicians and the general population in the tendency of wanting to offer help to those suffering from schizophrenia (physicians = 58 % versus general population : 45 %). Also, a higher percentage of physicians (72 %) have expressed feelings of compassion towards patients with schizophrenia versus 27 % in the general population. Results indicate that physicians, with a family member suffering from schizophrenia, are less comfortable discussing openly about the family member’s illness (26 % versus 48 %). With regards to preconception of the severity of schizophrenia, in the field of health, and more specifically mental health, there are no differences observed amongst the physicians and the general population.En este artículo, los autores presentan los resultados concernientes a la percepción y las actitudes de los médicos generales de Québec con respecto a los pacientes que sufren de esquizofrenia y comparan los datos obtenidos a través de una encuesta con aquellos obtenidos gracias a 5 preguntas comunes realizadas a la población quebequense en general. Se propuso a los médicos generales de Québec un cuestionario corto, compuesto de 5 temas escogidos previamente a partir de un cuestionario más largo y presentado a la población en general. Estos temas exploran la percepción y la actitud de los médicos en relación con la esquizofrenia. Un poco más de mil (1,003) médicos generales (46% de las mujeres y 54% de los hombres) respondieron a partir de una muestra aleatoria. De los 3,500 cuestionarios enviados, la tasa de respuesta fue de 29%. Los autores constataron diferencias significativas entre los médicos generales y la población quebequense en general en cuanto a la tendencia a querer ofrecer ayuda a las personas que sufren de esquizofrenia (médicos generales = 58% comparado con la población general: 45%). Del mismo modo, un porcentaje mayor de médicos generales (72%) dijeron sentir compasión por los pacientes que sufren de esquizofrenia, comparado con 27% de la población en general. Los médicos dijeron sentirse menos cómodos para discutir abiertamente acerca de la enfermedad con un miembro de la familia si éste sufre de esquizofrenia (26% comparado con 48%). No hubo diferencia entre las dos poblaciones en cuanto al juicio de la severidad de la esquizofrenia en el campo de las enfermedades, incluyendo las enfermedades mentales.Neste artigo, os autores apresentam resultados a respeito da percepção e das atitudes dos médicos generalistas do Quebec com respeito aos pacientes que sofrem de esquizofrenia e comparam os dados obtidos com uma sondagem aos obtidos graças a cinco questões comuns enviadas à população quebequense em geral. Um curto questionário, composto de cinco itens escolhidos previamente a partir de um questionário mais abrangente e apresentado à população em geral, foi proposto aos médicos generalistas do Quebec. Estes itens sondavam a percepção e a atitude dos médicos com respeito à esquizofrenia. Pouco mais de mil médicos generalistas (1.003 - 46% mulheres e 54% homens) responderam a partir de uma amostragem aleatória. Dos 3.500 questionários enviados, a taxa de resposta foi de 29%. Os autores constataram diferenças importantes entre os médicos generalistas e a população quebequense em geral na tendência de querer oferecer ajuda às pessoas que sofrem de esquizofrenia (médicos generalistas: 58% versus população geral: 45%). Igualmente, uma porcentagem mais alta de médicos generalistas (72%) disseram sentir compaixão pelos pacientes que sofrem de esquizofrenia, versus 27% na população em geral. Os médicos generalistas disseram sentir-se menos à vontade para discutir abertamente sobre a doença a um membro da família, se este sofrer de esquizofrenia (26% versus 48%). Não havia diferença entre as duas populações com respeito ao julgamento da gravidade da esquizofrenia no campo das doenças, incluindo doenças mentais

Perspective d’usagers suivis en clinique externe d’établissements de première, deuxième et troisième lignes

L'étude regroupe les résultats de quatre enquêtes majeures sur la satisfaction de la clientèle de services de consultation externe en santé mentale de Montréal. Elle implique des milieux offrant des services de base, des services spécialisés et des services ultra-spécialisés. Effectuée à l'aide d'entrevues individuelles auprès d'un total de 856 patients, elle a permis de documenter la perspective de ces usagers. Les principales tendances observées indiquent que les patients sont généralement très satisfaits de la façon d'être des intervenants et de l'alliance thérapeutique établie avec eux. L'organisation et le fonctionnement des services génèrent toutefois des taux de satisfaction nettement inférieurs. Ces résultats semblent refléter l'impact des transformations récentes dans le système de services en santé mentale.This study is based on results of four major surveys on the satisfaction of the clientele regarding external consultation of mental health services in Montréal. It covers milieux offering primary care, specialized and ultra-specialized services. Conducted with 856 patients through personal interviews, this study has allowed to document consumers' perspectives. The major tendencies observed indicate that patient are generally highly satisfied with the work of mental health professionals and the therapeutic alliance they establish with them. Organization as well as functioning of services however, generate less satisfaction. These results appear to reflect the impact of recent transformation of the mental health system.El estudio reagrupa los resultados de cuatro grandes encuestas sobre la satisfacción de la clientela de los servicios de consulta externa en salud mental de Montreal. Esta implica los medios que ofrecen servicios de base, servicios especializados y servicios ultra especializados. Efectuada por medio de entrevistas individuales a 856 pacientes, la misma ha permitido documentar la perspectiva de estos usuarios. Las principales tendencias observadas indican que en general los pacientes se encuentran satisfechos de la manera de ser de los trabajadores y de la alianza terapéutica que se ha establecido con ellos. La organización y el funcionamiento de los servicios generan sin embargo algunos porcentajes de satisfacción, netamente inferiores. Estos resultados parecen reflejar el impacto de las recientes transformaciones en el sistema de servicios en salud mental

Sur la première ligne : sondage pour un partage. Les omnipraticiens et la schizophrénie

Contexte : Les omnipraticiens (MFs) jouent un rôle prépondérant dans le traitement des patients atteints de schizophrénie. Buts : Découvrir le nombre de patients atteints de schizophrénie qui sont traités par les MFs ; les besoins et attitudes des MFs, leurs connaissances en matière de diagnostic, et le traitement qu’ils prodiguent. Méthodologie : Un sondage postal a été conduit auprès de MFs du Québec choisis de façon aléatoire. Résultats : Un total de 1 003 MFs ont répondu au sondage. Parmi eux, un faible pourcentage a à rencontrer une schizophrénie débutante et les MFs désirent être plus informés sur l’accessibilité aux services des spécialistes. Les résultats objectivés aux questions portant sur les diagnostics et les connaissances sur les traitements sont inconsistants. La majorité des MFs traite les premiers épisodes psychotiques avec des antipsychotiques. Seulement un tiers d’entre eux proposent de maintenir le traitement après un premier épisode psychotique, conformément aux recommandations internationales et au récent guide de pratique canadien qui préconisent au moins de 6 à 12 mois de traitement après la réponse clinique partielle ou complète. Le temps consacré par les MFs masculins à un premier contact s’étale entre 10 et 20 minutes, tandis que 80 % des MFs femmes y consacrent au moins 20 minutes Les effets secondaires des antipsychotiques les plus préoccupants sont les gains de poids avant les signes neurologiques. Conclusion : un certain nombre de données de ce sondage devraient être reprises par les différentes associations professionnelles et gouvernementales, afin de bonifier la place des MFs dans un plan de santé à l’égard de la schizophrénie.Context: General practitioners (GP) play a preponderant role in the treatment of patients suffering of schizophrenia. Objectives: Discovering the number of patients with schizophrenia who are treated by GPs ; the needs and attitudes of GPs, their knowledge concerning diagnosis, and the treatment they provide. Methodology: A postal survey was conducted with Quebec GPs who were randomly chosen. Results: A total of 1 003 GPs have participated in the survey. Among them, a small percentage have to treat an early onset schizophrenia and the GPs have expressed their wish to be more informed on the accessibility of specialized services. Results pertaining to questions on diagnoses and knowledge on treatments are inconsistent. The majority of GPs treat the first psychotic episodes with antipsychotic medication. Only a third of GPs surveyed propose maintaining the treatment after a first psychotic episode, in accordance with international recommendations and the recent Canadian guidelines on practices that recommends at least 6 to 12 months of treatment after a partial or complete clinical response. Time given by male GPs to a first contact varies between 10 and 20 minutes, while 80 % of female GPs spend at least 20 minutes. The adverse effects of antipsychotic medication that raise most concern is weight gain before neurological signs. Conclusion: some of this survey’s data should be considered by various professional and governmental associations, in order to improve the place of GPs in a health plan destined to treat schizophrenia.Contexto: Los médicos familiares (MFs) desempeñan un papel preponderante en el tratamiento de pacientes que sufren de esquizofrenia. Objetivos: Descubrir el número de pacientes que sufren de esquizofrenia y que son tratados por los MFs; las necesidades y actitudes de los MFs, sus conocimientos en materia de diagnóstico y el tratamiento que ofrecen. Metodología: Se realizó una encuesta por correo con los MFs de Quebec elegidos de modo aleatorio. Resultados: Un total de 1,003 MFs respondieron a la encuesta. Entre ellos, un porcentaje bajo han encontrado una esquizofrenia inicial y los MFs desean estar más informados sobre la accesibilidad a los servicios de los especialistas. Los resultados asociados a las preguntas sobre los diagnósticos y los conocimientos acerca de los tratamientos son inconsistentes. La mayoría de los MFs tratan los primeros episodios psicóticos con antipsicóticos. Solamente un tercio de ellos propone mantener el tratamiento después de un primer episodio psicótico, conforme a las recomendaciones internacionales y a la reciente guía de práctica canadiense que preconiza al menos de 6 a 12 meses de tratamiento después de la respuesta clínica parcial o completa. El tiempo consagrado por los MFs masculinos en un primer contacto se extiende de 10 a 20 minutos, mientras que el 80% de los MFs femeninas consagran al menos 20 minutos. Los efectos secundarios de los antipsicóticos más preocupantes son el aumento de peso antes que los signos neurológicos. Conclusión: un cierto número de datos de esta encuesta deberían ser retomados por las diferentes asociaciones profesionales y gubernamentales a fin de bonificar el lugar de los MFs en un plan de salud con respecto a la esquizofrenia.Contexto: os clínicos gerais (médicos de família - MFs) representam um papel preponderante no tratamento dos pacientes que sofrem de esquizofrenia. Objetivos: descobrir o número de pacientes que sofrem de esquizofrenia que são tratados por MFs, as necessidades e atitudes dos MFs, seus conhecimentos em matéria de diagnóstico, e o tratamento que prescrevem. Metodologia: uma sondagem postal foi realizada com MFs do Quebec, escolhidos de maneira aleatória. Resultados: um total de 1.003 MFs responderam à sondagem. Dentre eles, uma pequena porcentagem encontrou uma esquizofrenia inicial e os MFs desejam ser melhor informados sobre a acessibilidade aos serviços de especialistas. Os resultados obtidos com as questões sobre os diagnósticos e os conhecimentos sobre os tratamentos são inconsistentes. A maioria dos MFs trata os primeiros episódios psicóticos com antipsicóticos. Apenas um terço dentre eles propõe manter o tratamento após um primeiro episódio psicótico, conforme as recomendações internacionais e o recente guia de prática canadense, que preconiza pelo menos 6 a 12 meses de tratamento após a resposta clínica parcial ou completa. O tempo dedicado pelos MFs masculinos a um primeiro contato dura entre 10 e 20 minutos, ao passo que 80% das MFs femininas consagram, pelo menos, 20 minutos. O efeito colateral dos antipsicóticos mais inquietante é o aumento de peso antes dos sinais neurológicos. Conclusão: um certo número de dados desta sondagem deverão ser retomados por diferentes associações profissionais e governamentais, a fim de melhorar a importância dos MFs em um plano de saúde com respeito à esquizofrenia

Real-Time Experimental Comparison of Two Depth Control Schemes for Underwater Vehicles Regular Paper

International audienceThis paper deals with an experimental comparison be‐ tween the proportional integral derivative (PID) control law and the adaptive nonlinear state feedback control, both applied on the AC-ROV underwater vehicle. The experi‐ mental results evaluate the closed-loop behaviour of the system under each controller in various operating condi‐ tions in order to compare how robust they are towards parameters' change and how they can reject external disturbances. It was concluded that the adaptive controller ensures a faster convergence and can adapt to a change of parameters as well as compensate for external disturban‐ ces. The PID needs to be retuned for every parameter change and is more sensitive to external disturbances

Clinical utility of combinatorial pharmacogenomic testing in depression: A Canadian patient- and rater-blinded, randomized, controlled trial

The pharmacological treatment of depression consists of stages of trial and error, with less than 40% of patients achieving remission during first medication trial. However, in a large, randomized-controlled trial (RCT) in the U.S. (“GUIDED”), significant improvements in response and remission rates were observed in patients who received treatment guided by combinatorial pharmacogenomic testing, compared to treatment-as-usual (TAU). Here we present results from the Canadian “GAPP-MDD” RCT. This 52-week, 3-arm, multi-center, participant- and rater-blinded RCT evaluated clinical outcomes among patients with depression whose treatment was guided by combinatorial pharmacogenomic testing compared to TAU. The primary outcome was symptom improvement (change in 17-item Hamilton Depression Rating Scale, HAM-D17) at week 8. Secondary outcomes included response (≥50% decrease in HAM-D17) and remission (HAM-D17 ≤ 7) at week 8. Numerically, patients in the guided-care arm had greater symptom improvement (27.6% versus 22.7%), response (30.3% versus 22.7%), and remission rates (15.7% versus 8.3%) compared to TAU, although these differences were not statistically significant. Given that the GAPP-MDD trial was ultimately underpowered to detect statistically significant differences in patient outcomes, it was assessed in parallel with the larger GUIDED RCT. We observed that relative improvements in response and remission rates were consistent between the GAPP-MDD (33.0% response, 89.0% remission) and GUIDED (31.0% response, 51.0% remission) trials. Together with GUIDED, the results from the GAPP-MDD trial indicate that combinatorial pharmacogenomic testing can be an effective tool to help guide depression treatment in the context of the Canadian healthcare setting (ClinicalTrials.gov NCT02466477)

Pharmacotherapy of Schizophrenic Patients: Preponderance of Off-Label Drug Use

Multiple drug class combinations are often prescribed for the treatment of schizophrenia, although antipsychotic monotherapy reflects FDA labeling and scientific justification for combinations is highly variable. This study was performed to gain current data regarding drug treatment of schizophrenia as practiced in the community and to assess the frequencies of off-label drug class combinations. 200 DSM IV-diagnosed schizophrenic patients recruited from community treatment sources participated in this cross-sectional study of community based schizophrenic patients. Drug class categories include First and Second Generation Antipsychotic drugs (FGA and SGA, respectively), mood stabilizers, antidepressants and anti-anxiety drugs. 25.5% of patients received antipsychotic monotherapy; 70% of patients received an antipsychotic and another drug class. A total of 42.5% of patients received more than one antipsychotic drug. The most common drug class combination was antipsychotic and a mood stabilizer. Stepwise linear discriminant function analysis identified the diagnosis of schizoaffective schizophrenia, history of having physically hurt someone and high scores on the General Portion of the PANSS rating scale predicted the combined use of an antipsychotic drug and a mood stabilizer. “Real world” pharmacotherapy of schizophrenia has developed its own established practice that is predominantly off-label and may have outstripped current data support. The economic implications for public sector payers are substantial as well as for the revenue of the pharmaceutical industry, whose promotion of off-label drug use is an increasingly problematic. These data are consistent with the recognition of the therapeutic limitations of both first and second generation antipsychotic drugs