Grant: Project Grant

Depression is a devastating chronic illness with incidence in women two times higher than in men. Current antidepressant therapies have notable limitations, showing only moderate efficacy, slow onset of action, and a relatively high rate of treatment resistance. Although gender-specific approaches to healthcare in neuropsychiatry are essential to improve on existing therapies, development of new treatment strategies are dependent upon preclinical research to provide a basic understanding of how sex, and female cycling, contribute to disease pathology. Unfortunately, current preclinical research focuses predominantly on male responses, leaving a gross knowledge gap which limits the development of more personalized treatments. Our preliminary evidence indicates that sex differences in brain communication patterns may play a role in depression susceptibility. Therefore, we will evaluate sex differences in the innate and stress-induced functionality of brain electrical output and communication, and responsiveness of these neural network activity patterns to various therapeutic drugs using animal models of depression. We will identify the impact of fluctuating female hormones on these physiological processes, and additionally, discern a role for the protein GSK-3 in their regulation. Importantly, we will identify how the efficacy of antidepressants to normalize these electrical patterns in depression model systems is influenced by cyclic changes in female hormone levels.