Grant: Doctoral Research Award: Canada Graduate Scholarships

Major depressive disorder (MDD), commonly referred to as depression, is a mental disorder that is a leading cause of disability and suicide worldwide. Afflicting millions of Canadians, MDD is the most common outcome of chronic stress, with women twice as likely to develop MDD as men. Antidepressant drugs and counselling are available to treat MDD but have variable outcomes. A better grasp of the biological causes of MDD is vital for developing improved treatment strategies. Growing evidence suggests that inflammation may lead to poor treatment outcomes in MDD and could be an important target for new medicines to treat MDD. The human immune system produces a protein called CD5 antigen-like (CD5L), which is elevated in the blood of men with MDD, but not in women who are more susceptible to developing inflammation under chronic stress. CD5L could be a protective factor against inflammation and depression in males, but not females. Here, I will investigate CD5L's ability to control brain inflammation and protect against depression, as well as explore how this protection differs with sex. Using a preclinical mouse model of human depression, I will subject mice of both sexes to chronic stress and evaluate differences in the onset of behaviours related to depression, between mice that have healthy levels of CD5L and mice lacking this protein. I will dissect brains from these mice to compare signs of inflammation, determine whether there are any differences in brain immune cell function during chronic stress, and assess the impact of adding CD5L. Lastly, I will study the biological properties of CD5L, to help understand sex-dependent factors protecting against depression and guide the design of new anti-MDD drugs. Ultimately, discovery of more effective methods to treat MDD will help to alleviate the social and economic burden of this disease.