Grant: Project Grant

50% of clinical depression cases are treatment resistant, most likely because clinical depression is composed of multiple biological changes, and these changes may vary from one case to another. We think the approach to overcoming treatment resistance is to discover these key biological changes and to match treatment to such changes so as to improve rates of treatment response. We think 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. We also think it is also likely to be elevated in clinical depression with head injury (Head injuries are associated with much higher rates of clinical depression). In this study we will use a special brain imaging method to measure MAO-B levels and determine if they are elevated in people with clinical depression as well as clinical depression with head injury. Then we will study, in people with clinical depression, and clinical depression with head injury unresponsive to treatment, whether cases 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 and clinical depression with comorbid head injury. 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.