Precision-medicine findings from the FACE-SZ cohort to develop motivation-enhancing programs in real-world schizophrenia

Background: In people with schizophrenia, major areas of everyday life are impaired, including independent living, productive activities, social relationships and overall quality of life. Enhanced understanding of factors that hinder real-life functioning is vital for treatments to translate into more positive outcomes. Aim: The goal of the present study was to identify factors associated with motivation deficits in real-life schizophrenia, and to assess its contribution to impaired functioning and quality of life. Methods: Based on previous literature and clinical experience, several factors were selected and grouped into factors potentially explaining motivation deficits. Some of these variables were never investigated before in relationship with motivation deficits. Results: In 561 patients with schizophrenia of the national FACE-SZ cohort living in the community, 235 (41.9%) reported severe motivation deficits. These deficits were found to be significantly associated with impaired socially useful activities, psychological and physical quality of life (in almost all domains), alcohol use disorder (aOR = 2.141, p = 0.021), severe nicotine dependence (aOR = 2.906, p < 0.001) independently of age and sex. No significant association was found for body mass index, metabolic syndrome or physical activity level. In the second model, we identified the following modifiable factors associated with motivation deficits: history of suicide attempt (aOR = 2.297, p = 0.001), positive symptoms (aOR = 1.052, p = 0.006), current major depressive episode (aOR = 2.627, p < 0.001), sleep disorders (aOR = 1.474, p = 0.024) and lower medication adherence (aOR = 0.836, p = 0.001) independently of gender, current alcohol use disorder, second-generation antipsychotics and akathisia. No significant association was found for negative symptoms, childhood trauma and inflammation. These results were maintained after removing patients with schizoaffective disorders or those with major depressive disorder. Interpretation: Motivation deficits are frequent and remain persistent unmet need in real-world schizophrenia that should be addressed in future guidelines. Based on our results, literature and clinical experience, we recommend to address in priority major depression, sleep, suicide, positive symptoms (when present and as early as possible) and medication adherence to improve motivation deficits of schizophrenia. © 2022 Informa UK Limited, trading as Taylor & Francis Group.Sorbonne Universités à Paris pour l'Enseignement et la RechercheFondaMental-Cohorte

Recommandations du réseau des centres experts schizophrénie pour le dépistage, la prévention, et le traitement des troubles du sommeil dans la schizophrénie

Contexte : les facteurs associés aux troubles du sommeil ont été peu explorés dans la schizophrénie. La littérature scientifique suggère une fréquence importante et hétérogène de ces troubles.Objectifs : les objectifs de la présente étude étaient de déterminer la prévalence et les facteurs de risque associés aux troubles du sommeil dans la schizophrénie à partir de la cohorte nationale en vie réelle FACE-SZ.Matériels et méthodes : des patients pris en charge en ambulatoire avec une schizophrénie stabilisée ont été recrutés au sein de 10 centres experts - schizophrénie. La qualité du sommeil a été explorée à l’aide de l’index de qualité du sommeil de Pittsburgh (PSQI). Les troubles du sommeil étaient définis par un score PSQI > 5. La sévérité psychotique a été mesurée avec l’échelle des syndromes positifs et négatifs (PANSS), la présence actuelle d’un épisode dépressif caractérisé avec l’échelle de dépression pour la schizophrénie de Calgary (CDSS), l’agressivité verbale avec le questionnaire d’agressivité de Buss et Perry (BPAQ), l’adhésion aux traitements avec l’échelle de cotation de l’adhésion aux traitements (MARS), l’akathisie avec l’échelle d’akathisie de Barnes (BAS). Les comorbidités somatiques actuelles ainsi que l’indice de masse corporelle ont été recueillis. Les variables avec une valeur de p < 0,20 dans les analyses univariées ont été incluses dans le modèle de régression multivarié.Résultats : 327 sujets parmi les 562 inclus (58,2%, intervalle de confiance à 95% [54,1% - 62,3%]) ont rapporté avoir des troubles du sommeil. Après ajustement, les troubles du sommeil étaient significativement associés à la migraine (rapport de côtes ajusté RCa = 2,23, p = 0,041), à l’épisode dépressif caractérisé (RCa = 1,79, p = 0,030), à la mauvaise adhésion aux traitements (RCa = 0,87, p = 0,006), à l’akathisie (RCa = 1,29, p = 0,042), et à l’agressivité verbale (RCa = 1,09, p = 0,002).Conclusion : d’après nos résultats, plus d’un patient ambulatoire sur deux, avec une schizophrénie stabilisée, présenteraient des troubles du sommeil. En accord avec les données de la littérature scientifique, nous avons émis des recommandations d’experts pour le traitement et la prévention des troubles du sommeil. Nous recommandons entre autres de traiter les épisodes dépressifs caractérisés comorbides ainsi que la migraine, et d’adapter le traitement antipsychotique afin d’améliorer l’adhésion et l’akathisie

Microbiota-Orientated Treatments for Major Depression and Schizophrenia

International audienceBackground and significance. There is a need to develop new hypothesis-driven treatment for both both major depression (MD) and schizophrenia in which the risk of depression is 5 times higher than the general population. Major depression has been also associated with poor illness outcomes including pain, metabolic disturbances, and less adherence. Conventional antidepressants are partly effective, and 44% of the subjects remain unremitted under treatment. Improving MD treatment efficacy is thus needed to improve the SZ prognosis. Microbiota-orientated treatments are currently one of the most promising tracks. Method. This work is a systematic review synthetizing data of arguments to develop microbiota-orientated treatments (including fecal microbiota transplantation (FMT)) in major depression and schizophrenia. Results. The effectiveness of probiotic administration in MD constitutes a strong evidence for developing microbiota-orientated treatments. Probiotics have yielded medium-to-large significant effects on depressive symptoms, but it is still unclear if the effect is maintained following probiotic discontinuation. Several factors may limit MD improvement when using probiotics, including the small number of bacterial strains administered in probiotic complementary agents, as well as the presence of a disturbed gut microbiota that probably limits the probiotics' impact. FMT is a safe technique enabling to improve microbiota in several gut disorders. The benefit/risk ratio of FMT has been discussed and has been recently improved by capsule administration. Conclusion. Cleaning up the gut microbiota by transplanting a totally new human gut microbiota in one shot, which is referred to as FMT, is likely to strongly improve the efficacy of microbiota-orientated treatments in MD and schizophrenia and maintain the effect over time. This hypothesis should be tested in future clinical trials

The impact of parent history of severe mental illness on schizophrenia outcomes: results from the real-world FACE-SZ cohort

International audienceParent history of severe mental illness (PHSMI) may have long-term consequences in adult offspring due to genetic and early environmental factors in preliminary studies. To compare the outcomes associated in subjects with PHSMI to those in patients without PHSMI. The participants with schizophrenia and schizoaffective disorders were recruited in the ongoing FACE-SZ cohort at a national level (10 expert centers) and evaluated with a 1-day-long standardized battery of clinician-rated scales and patient-reported outcomes. PHSMI was defined as history of schizophrenia or bipolar disorders in at least one parent and was included as explanatory variable in multivariate models. Of the 724 included patients, 78 (10.7%) subjects were classified in the PHSMI group. In multivariate analyses, PHSMI patients had a better insight into schizophrenia and the need for treatment and reported more often childhood trauma history compared to patients without PHSMI. More specifically, those with paternal history of SMI reported more severe outcomes (increased childhood physical and emotional abuses, comorbid major depression and psychiatric hospitalizations). PHSMI is associated with increased risk of childhood trauma, major depressive disorder and psychiatric hospitalization and better insight in individuals with schizophrenia. Specific public health prevention programs for parents with SMI should be developed to help protect children from pejorative psychiatric outcomes. PHSMI may also explain in part the association between better insight and increased depression in schizophrenia

Recommendations of the Schizophrenia Expert Center network for adequate physical activity in real-world schizophrenia (FACE-SZ)

International audienceThe World Health Organization (WHO) recommends adults complete 150-300 min per week of moderate physical activity or 75-150 min of vigorous physical activity or an equivalent combination of both, to optimize health. To explore the factors associated with adequate MVPA in stabilized outpatients with schizophrenia. 425 stabilized outpatients were recruited in the national FACE-SZ cohort between 2015 and 2018 were evaluated with the International Physical Activity Questionnaire and a 1-day long standardized battery. We explored in multivariate analyses the clinical and pharmacological factors associated with MVPA (model 1) and the biological factors and patient-reported outcomes (model 2). Overall, only 86 (20.2%) of the 425 participants achieved the recommended MVPA threshold. In model 1, the adequate MVPA group was associated with younger age, mood stabilizers prescription and adherence to treatment, independent of sex, positive and depressive symptoms, first-generation antipsychotics prescription, anxiolytic medication, and akathisia. In model 2, adequate MVPA was associated with better glycemic and lipidic profile and better physical and psychological well-being, self-esteem, sentimental life, and resilience independently of age, sex, and current psychotic severity. The expert centers recommend the importance of promoting promote effective MVPA programs for stabilized patients with schizophrenia. Interventions studies suggest that MVPA may be a useful strategy to maximize physical and psychological well-being and self-esteem and potentially to prevent or manage metabolic disturbances