Description du projet
Corrélation entre la maladie mentale et les comorbidités associées
Les troubles psychiatriques graves, tels que la psychose, la dépression et le trouble bipolaire, ont un impact socio-économique considérable. L’identification des mécanismes de causalité entre ces troubles et leurs comorbidités, telles que les maladies cardiovasculaires ou la toxicomanie, est primordiale. Le projet UNRAVEL-CAUSALITY, financé par l’UE, entend déterminer si la maladie mentale entraîne des comorbidités ou si les comorbidités augmentent le risque de maladie mentale ou sa gravité. Le projet adoptera une approche interdisciplinaire, combinant des méthodes causales épidémiologiques et génétiques, des analyses longitudinales, une équation structurelle génomique modélisée et une randomisation mendélienne, pour établir la causalité. Les résultats amélioreront notre compréhension des symptômes psychiatriques, ainsi que des stratégies de prévention et de traitement. En mettant ces relations complexes en lumière, le projet améliorera les résultats en matière de santé mentale pour les personnes souffrant de troubles psychiatriques graves.
Objectif
Serious mental illness – depression, bipolar, and psychotic disorder – is among the leading causes of disability worldwide, disproportionately affecting people of non-European ancestry. On top of the burden posed by its symptoms, mental illness is also associated with comorbid health problems. The two most important ‘comorbidities’ of mental illness, given their driving role in decreasing quality and duration of life, are substance (mis)use and cardiovascular disease. Whether these comorbidities arise due to causal relationships is surprisingly unclear. The causal direction is also uncertain: does mental illness lead to comorbidities, and / or do comorbidities increase the risk of (more severe) mental illness? Through several prestigious fellowships, I have established myself as an expert in epidemiological and genetic causal inference methods. In this ambitious project, I will bring together innovative approaches to unravel the relationships of mental illness with substance (mis)use and cardiovascular disease. My aims are to: 1) assess bidirectional relationships between mental illness and its comorbidities by conducting longitudinal analyses in (multi-ancestry) prospective cohort studies, 2) distinguish bidirectional relationships from shared genetic liability by jointly modelling the complete genetic architecture of mental illness and its comorbidities (genomic structural equation modelling), 3) establish causality by using only highly significant genetic variants as instruments for one variable and testing causal effects on another (Mendelian randomization), 4) fully unravel the nature of relationships between mental illness and its comorbidities by ‘triangulating’ evidence from aims 1 to 3, and 5) assess how informing medical doctors about the outcomes of aim 4 influences their clinical decisions in a randomized online experiment. This interdisciplinary project sets the stage for more effective prevention and treatment of mental illness, across ancestry groups.
Mots‑clés
Programme(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Thème(s)
Régime de financement
HORIZON-ERC - HORIZON ERC GrantsInstitution d’accueil
1081 HV Amsterdam
Pays-Bas