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Mental illness, substance use, and cardiovascular disease: Unravelling causal relationships

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

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Programme(s)

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Topic(s)

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Funding Scheme

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HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) ERC-2022-STG

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Host institution

STICHTING AMSTERDAM UMC
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 1 500 000,00
Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 1 500 000,00

Beneficiaries (1)

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