Grant: CIHR Fellowship

According to the World Health Organization, in countries like Canada, clinical depression is the leading cause of death and disability. Four per cent of Canadians suffer from clinical depression, and in half of these cases the clinical depression is treatment resistant. We think that one cause of treatment resistance is that commonly used current treatments which raise a brain chemical called serotonin miss key brain changes in clinical depression. We think the approach to overcoming treatment resistance is to discover these key biological changes and to carefully match treatment to such changes so as to improve rates of treatment response. We have begun to discover a new biological change in clinical depression, which is increased levels of a protein in the brain called MAO-B. MAO-B has several properties, including having an effect opposite to antioxidants, and removing brain chemicals that support normal mood. In this study, using a unique brain imaging technology only available in Toronto, we will determine whether MAO-B level is increased in brain regions that influence mood during clinical depression and treatment resistant clinical depression. Then we will study whether cases of clinical depression with elevated MAO-B levels will preferentially respond to a special antidepressant that shuts down MAO-B. These are the first definitive studies of MAO-B in clinical depression. If we find that elevated MAO-B predicts clinical response to the treatment that shuts down MAO-B, this could be developed as a new way to match specific treatment to specific biology in clinical depression so as to get better treatment outcomes.