About a billion people live with mental illness (including severe mental illness (SMI) such as schizophrenia spectrum disorder, bipolar disorder, and major depressive disorder) globally, which present a major global and economic health burden. SMI patients have shorter life expectancy (5-20 years on average) and are at a greatly increased risk of dementia mainly attributed to accelerated brain aging. However, the risk factors for accelerated brain aging in SMI remain unknown. In this project, we will jointly analyze both structural and functional imaging data to study brain aging trajectories among individuals with SMI in the UK Biobank, capturing the different temporal, spatial, and biological characteristics in assessing brain age. We will further integrate with multi-omics (e.g. genotype and metabolite profiles) and lifestyle (e.g. smoking, alcohol drinking, diet, obesity and physical activity) data available in UK Biobank to identify the genetic and lifestyle risk and protective factors that modulate accelerated brain aging in SMI. Our specific aims (SA) are: SA1. To identify the genetic risk and protective factors of brain aging. SA2: To identify the lifestyle risk and protective factors of brain aging. The project will last for 3 years from beginning of 2023 to end of 2026. Our work addresses the global mental health issue and provides possible solutions to clinical implications for SMI patients, which can potentially reduce the excess morbidity and mortality of SMI and improve health of millions of people.
