Severe mental illnesses, including psychotic disorders, are associated with increased morbidity, mortality, and a significantly shortened lifespan. Recent evidence points to immune-metabolic dysfunction and alterations in brain structure and function as key contributors to these outcomes. However, the precise mechanisms remain unclear. This project will explore how these factors intersect to influence physical and mental health trajectories in individuals with severe mental illness, focusing on the following key areas:
1. Immune system dysfunction – We will analyse inflammatory markers, including cytokines, acute-phase proteins (e.g., CRP), and differential white blood cell counts, to explore how immune dysregulation contributes to health outcomes in severe mental illness.
2. Metabolic markers – We will assess metabolic dysfunction, including insulin resistance, lipid profiles, and other biomarkers of metabolic disturbances, to determine their role in psychosis and related disorders.
3. Neuroimaging – Structural and functional MRI data will be used to examine how immune-metabolic dysfunction relates to brain structure, cognitive performance, and connectivity alterations in key neural networks.
4. Cardiovascular and other physical health measures – We will investigate cardiovascular health using ECG and cardiac MRI, alongside other physical health measures (e.g., BMI) to understand how systemic health trajectories intersect with mental illness.
5. Genetic and environmental contributions – We will explore how polygenic risk scores for psychiatric, cardiovascular, and metabolic conditions, along with early-life environmental exposures (e.g., childhood trauma, cannabis use), impact immune-metabolic dysfunction and brain health. We will also include DNA methylation data and transcriptome-wide association studies (TWAS) to further investigate molecular signatures.
