Grant: CIHR Fellowship

Mental illnesses like anxiety and depression affect more than 20% of the Canadian population, and lead to an economic burden at the population level of an estimated $51 billion per year. A common risk factor for these conditions is adversity or abuse during early life. Interestingly, even during prenatal development, exposure to stress or adversity in the mother can be transferred to the fetus brain, and subsequently can permanently affect how the stress hormone system is regulated. Given the prevalence of mental illnesses and the role of stress in causing them, it is imperative to learn more about the biological mechanisms involved and the system components where intervention is possible. Some progress has been made in elucidating the neurobiology of stress, but many questions cannot be addressed with current tools, which include animal models and 2-dimensional human cell culture systems. This proposal aims to establish 3-dimensional culture systems called cerebral organoids or "mini-brains" - stem-cell derived tissues that mimic the human brain - as research models for developmental psychiatric disturbances. Stress will be simulated in these cerebral organoids by manipulating the main hormone associated to stress, cortisol. Molecular mechanisms will be investigated comparing 'stressed' and 'unstressed' conditions in cerebral organoids by studying specialized cells types. This is important, because the human brain is very complex, and very different processes occur from cell to adjacent cell (i.e. neurons, etc.). Comparing findings from this model to evidence from brains of individuals who experienced severe adversity during early childhood and subsequently suffered from depression in adulthood, will allow placement of our findings into the clinical context. The outcomes from this research have the potential to expedite identification of at-risk populations, and even guide development of intervention strategies.