Grant: Team Grant: CEEHRC Phase II

The Mental Health Commission of Canada has estimated the cost of mood disorders to be $50B/year, with a dramatic rise expected in the near future. Therefore, uncovering disease mechanisms and risk factors is of great importance as well as of scientific interest. A major priority is the identification of personalized disease signatures that promise a customized approach to predicting disease risks, prognosis, and to facilitate early and targeted interventions. Bipolar disorder (BPD) is a debilitating mood disorder that affects around 2.5-4% of the general population, with peak age of onset between 15-25 years old. Family history is the single most robust risk factor, yet there are no individual-specific predictors for BPD. Substantial evidence points to a strong association between an abnormal circadian rhythm and BPD. Circadian rhythmicity allows living organisms on earth to adapt to cyclical day and night changes. There are also studies that highlight the role of epigenetic factors (gene regulating "switches") in BPD. We recently discovered that epigenetic switches oscillate in a circadian fashion. This led us to a new theory that daily changes in epigenetic profiles gradually accumulate mistakes and become major risk factors that disturb brain function and result in BPD. In this project, we propose a unique study of youths with high-risk of BPD. We will look at changes in epigenetic signatures prior to a crucial developmental time-frame for BPD susceptibility. Our goal is to identify molecular signatures that can be used for precise prediction of BPD, long before the onset of the disease. There is evidence that circadian epigenomes play a role in cancer, type 2 diabetes, and Alzheimer's disease. Principles developed in this project can be used in future circadian studies of other diseases. Linking individual molecular circadian changes with specific pathologies can create the foundation for new diagnostic and therapeutic tools in precision medicine.