Project description
How the mental illness and related comorbidities correlate
Severe psychiatric disorders, such as psychosis, depression, and bipolar disorder, have a significant socio-economic impact. Identifying the causative mechanisms between these disorders and their comorbidities, such as cardiovascular disease or substance misuse, is essential. The EU-funded UNRAVEL-CAUSALITY project aims to investigate whether mental illness leads to comorbidities or if comorbidities increase the risk of mental illness or its severity. The project will take an interdisciplinary approach, combining epidemiological and genetic causal methods, longitudinal analyses, model genomic structural equitation, and Mendelian randomisation to establish causality. The findings will enhance our understanding of psychiatric symptoms, as well as prevention and treatment strategies. By shedding light on these complex relationships, the project will improve mental health outcomes for individuals with severe psychiatric disorders.
Objective
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.
Keywords
Programme(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Topic(s)
Funding Scheme
HORIZON-ERC - HORIZON ERC GrantsHost institution
1081 HV Amsterdam
Netherlands