Grant: Project Grant

Major depression is defined by the World Health Organization as one of the highest burdens of disease particularly in the western world. One of the main epidemiological observations on major depression pertains to differences in incidence, prevalence, and prognosis between sexes. Design of novel, faster and more effective pharmacotherapeutic approaches for major depression should thereby focus not just on general understanding of novel antidepressant drugs actions and efficacy, but also on evaluating sex differences that may underlie some of the effects of these drugs, and thereby could be important for development of new therapies.. In the proposed research, we will evaluate the possibility that the extracellular matrix protein Reelin may have fast acting antidepressant effects (as based on our published results and other preliminary data) and will examine the putative molecular mechanisms of these actions. Reelin is differentially expressed in some brain regions of male and female rats, and reelin levels are differentially affected in both sexes in conditions of chronic stress. We believe that these differences on Reelin expression levels may relate to differences between sexes observed in clinical depression, and should be considered when developing Reelin-based therapeutics. We aim to explore these issues by carrying on studies on both animal models, and depression patients. Our hope is that these studies would illustrate the roles of Reelin in major depression in men and women and provide a novel venue for the development of new therapeutics for major depression.