Fondation FondaMental

Major Depressive Disorder (MDD) is a debilitating psychiatric disorder that is a leading cause of disability worldwide. Although treatment with antidepressants, such as Selective Serotonin Reuptake Inhibitors (SSRIs), has demonstrated clinical efficacy, the "trial and error" approach in choosing the most effective antidepressant treatment for each patient allows for only a subset of patients to achieve response to the first line of treatment. Circular RNAs (circRNAs), are highly stable and brain-enriched non-coding RNAs that are mainly derived from the backsplicing and covalent joining of exons and introns of protein-coding genes. They are known to be important for brain development and function, cross the blood-brain-barrier, and be highly sensitive to changes in both synaptic activity and neuronal receptor signaling. Here we present evidence that expression of the brain-enriched circRNA, CDR1as, is associated with symptomatic response to SSRI treatment, and regulated by serotonin and Brain-Derived Neurotrophic Factor (BDNF) receptor activity. We present data using circRNA-specific PCR in baseline whole blood samples from two independent cohorts, drawn from the Establishing moderators and biosignatures of antidepressant response in clinical care (EMBARC) and the Biomarkers of ANTidepressant RESponse (ANTARES) clinical studies, showing that before treatment CDR1as is differentially expressed between future symptomatic responders and non-responders to treatment with the SSRI sertraline. Additional data from naturalistic antidepressant response studies further highlight the association between CDR1as and antidepressant effects of SSRIs as a class. In addition, we show that CDR1as levels are altered following sertraline treatment in responders with the trajectory of change post-treatment associated with long-term remission. Furthermore, we report that levels of CDR1as in the blood can specifically predict remission with SSRI treatment, but not response/remission with Placebo or Bupropion treatments. Lastly, we provide evidence in animal mechanistic and neuronal culture studies, suggesting mouse Cdr1as is strongly regulated by 5-HT2A and BDNF receptor signaling. Taken together, our data identify a brain-enriched circRNA associated with known mechanisms of antidepressant response that can serve as a blood biomarker for predicting response and remission with SSRI treatment.

Health literacy influences the ability to understand, process, and act upon health-related information. In the context of oncology, this competence becomes particularly crucial given the high level of complexity associated with diagnoses, treatments, and care. Accordingly, a narrative literature review was conducted with the aim of identifying evidence-based interventions to promote health literacy in patients with oncological disease. Ten scientific articles published between 2019 and 2025 were selected. Geographically, these studies span four continents, demonstrating the global relevance and growing interest in health literacy research within oncology. The analysis identified ten categories of health literacy interventions: assessment, communication, patient navigation, education, awareness campaigns, professional training, organizational interventions, community-based and integrated interventions, research and monitoring, and cross-cutting interventions. These interventions were shown to have a positive impact on knowledge growth, treatment adherence, improved use of health services, and the promotion of person-centered care. It was concluded that individuals with higher levels of health literacy make more informed decisions regarding their health processes, contributing to health gains through person-centered care and to the sustainability of the healthcare system. Nevertheless, there remains a need for clearer conceptualization, standardized assessments, and more rigorous, comprehensive, and culturally adapted research to support the development and implementation of effective health literacy interventions.

Generative artificial intelligence, particularly large language models, offers an opportunity to rethink how patient-reported outcomes (PROs) are assessed and implemented in health systems. Despite decades of psychometric and digital innovation, PROs remain conceptually limited and underused in both clinical practice and AI models. Rooted in top-down, predefined instruments and assumptions of unidimensionality, traditional PROs struggle to capture the fluctuating and multidimensional nature of lived health experiences. In contrast, generative AI supports bottom-up, narrative-based approaches that process language in a flexible and context-aware way. Our viewpoint supports two distinct directions: one that refines current psychometric models through generative artificial intelligence integration, and another that embraces a more disruptive shift toward language-native tools capable of synthesising patient narratives. Realising this potential will require addressing key challenges, including validation, clinical actionability, equity, and trust. Bridging these gaps could make PROs a true lever for more personalised, meaningful, and inclusive care.

BackgroundWhile recovery orientation is national policy in many countries, evidence remains limited for the effectiveness at a service level. This paper describes the protocol for implementing a pro-recovery training intervention (REFOCUS-RETAFORM) in specialist mental health services across France. The aim is to evaluate whether REFOCUS-RETAFORM plus usual care leads to improved outcomes for adolescent and adult mental health service users compared with usual care alone.MethodsA two-step stepped wedge cluster randomised controlled trial will be conducted, with a nested qualitative sub-study exploring stakeholders’ views on changes in staff-user relationships and implementation influences. The REFOCUS-RETAFORM intervention is a training intervention for mental health staff, to develop recovery-promoting relationships and pro-recovery working practices. Clusters are services, which transition sequentially from control to intervention condition in a randomised order. Eight clusters are randomised to deliver REFOCUS-RETAFORM in year one and eight clusters in year two. Each cluster delivers REFOCUS-RETAFORM to two teams from their organisation (32 teams in total). Participants are a) service users aged 13–65 years attending services implementing REFOCUS-RETAFORM, and b) staff receiving the intervention. The primary outcome is the Questionnaire about the Process of Recovery. Secondary outcomes include perceived stigma and coercion, self-stigma and wellbeing for service users, and recovery-orientation for staff. Data will be collected from 540 service users (180 at baseline, 180 at month 12, 180 at month 24) and 220 staff. We will use multilevel mixed-effects models, adjusting for secular trends and thematic analysis for the qualitative interview data.DiscussionFindings will inform the continued transformation of French specialist mental health services toward a recovery orientation.Trial registrationClinical Trials NCT05824234, registered 21 April 2023.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12888-025-07253-w.

Recent studies on Metabolic dysfunction-associated fatty liver (MAFLD) in schizophrenia show inconsistent findings, often based on small or specific samples. This study aims to assess the prevalence of MAFLD and its sociodemographic, clinical, and treatment-related risk factors in a large cohort of chronic patients with schizophrenia. A secondary goal is to identify an immuno-inflammatory signature associated with MAFLD. 1009 stable outpatients with schizophrenia were included in the cross-sectional analysis. Individuals with liver disease, hepatitis B/C, or current alcohol use disorder were excluded. MAFLD was screened using the Fatty Liver Index (FLI), with FLI>60 indicating MAFLD. Risk factors were assessed using multivariate logistic regression, and inflammatory markers were analysed with penalized logistic regression. In a sample of 1009 individuals with schizophrenia, MAFLD prevalence was 36.6%, higher in men than in women (38.3% vs 32.0%, p<0.0001). Multivariate analysis identified male gender, older age, current smokers, mood stabilizers, antidepressant, clozapine, olanzapine and quetiapine as risk factors for MAFLD. The use of risperidone was associated with a lower risk of MAFLD (0.63 (0.42-0.94). Elevated levels of inflammatory markers such as TNF-α, CRP, and IL-12/IL-23p40 were also linked to a higher likelihood of MAFLD. Although not generalizable to all patients with schizophrenia, this study confirms the high prevalence of MAFLD in individuals with schizophrenia. Psychiatrists should promote healthy lifestyle changes, such as weight control, improved diet, better sleep, and increased physical activity, to improve both physical health and quality of life in these patients.