Grant: Project Grant

Although emotional "ups" and "downs" are a natural part of life, major depression results in a significant deviation from our normal patterns of thoughts, feelings and behaviors. Ranging from mild to severe, major depression robs its victims of the natural emotional "coloring" of life and creates a mental state that can best be described as "lifeless". It is estimated that about 8- 12% of Canadians will suffer from an episode of major depression during their lives. The emotional, societal and economic burden of the disease for the Canadian society is enormous. Feelings of hopelessness and guilt may pervade, along with significant disturbances in thought patterns, energy/motivation, sleep and appetite, in the pleasure in previously enjoyable activities, lack of concentration, and others. Despite the existence of pharmaceutical interventions for depression, their lack of clinical efficacy in approximately 30% of patients and delay in action (up to 3 weeks) points to a pressing need for research. It's often said that depression results from a chemical imbalance, notably of the neurotransmitter serotonin. However, that figure of speech dramatically falls short of providing a satisfactory explanation of how the activity of serotonin-secreting neurons in the brain operate. Indeed, mood-related networks in the brain constantly talk to one another to ultimately control key aspects of our behaviors such as motivation and decision-making process. We currently have a poor understanding of how these networks communicate and the nature of the signals that are being communicated. In this proposal, we propose to take advantage of recent technical developments to gain a better understanding of how brain networks involved in depression are functioning. These studies will significantly improve our current understanding and provide a rich framework that will contribute to the development of new and novel therapeutic strategies.