Grant: Doctoral: Vanier Canada Graduate Scholarships

Depression is a devastating disorder with incidence in women two times higher than in men, however little is known about the mechanisms that contribute to this increased vulnerability. Normal brain function requires coordinated electrical activity of networks for the communication within and between brain regions. Not only has the dysregulation of electrical activity been shown to play an important role in depression, the normalization of aberrant activity relates directly to treatment success. In these studies, sex differences in innate and stress-induced changes in the functionality of brain electrical output will first be evaluated using a rat model of depression. The goal is to assess the capacity of these electrical alterations to associate with and predict subsequent depression behaviours. In a second study, we will evaluate sex differences in antidepressant responsiveness using a specific diagnostic measure: the normalization of brain electrical patterns. In the final study we will evaluate whether sex differences in the activity of the protein GSK-3 influences brain electrical activity and depression behaviours, and whether suppressing GSK-3 activation can be protective for the development of depression. In all studies, female cycling will be monitored to determine the relationship between the reproductive cycle and changes in brain patterns and behaviour. The goal of these studies is to take a novel approach to evaluate how brain regions are functionally linked in depression, and to identify critical sex differences in brain electrical patterns that may contribute to, or predict, depression susceptibility and drug responsiveness. This research will identify a potential mechanism by which brain activity may be regulated in a sex-dependent manner, via GSK-3. The results will identify electrical patterns that may serve as biomarkers for depression and will lead to more personalized therapies to offer significantly improved health outcomes for this disorder.