Descripción del proyecto
Cómo se correlacionan las enfermedades mentales y sus enfermedades concomitantes
Los trastornos psiquiátricos graves, como la psicosis, la depresión y el trastorno bipolar, tienen un impacto socioeconómico importante. Es esencial identificar los mecanismos causales entre estos trastornos y sus enfermedades concomitantes, como las enfermedades cardiovasculares o el abuso de sustancias. El equipo del proyecto UNRAVEL-CAUSALITY, financiado con fondos europeos, se propone investigar si las enfermedades mentales conducen a enfermedades concomitantes o si estas aumentan el riesgo de padecer enfermedades mentales o su gravedad. Se adoptará un enfoque interdisciplinario, combinando métodos causales epidemiológicos y genéticos, análisis longitudinales, equiparación estructural genómica de modelos y aleatorización mendeliana para establecer la causalidad. Los hallazgos mejorarán nuestra comprensión de los síntomas psiquiátricos, así como las estrategias de prevención y tratamiento. Al arrojar luz sobre estas complejas relaciones, los investigadores mejorarán los resultados en materia de salud mental de personas con trastornos psiquiátricos graves.
Objetivo
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.
Palabras clave
Programa(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Régimen de financiación
HORIZON-ERC - HORIZON ERC GrantsInstitución de acogida
1081 HV Amsterdam
Países Bajos