Brain exosome biomarker targets to optimize pharmacologic treatment of depression in pregnancy

点击翻译按钮获取中文摘要

This proposal aims to determine whether biomarkers in central nervous system-derived exosomes are useful predictors of functional drug activity in the maternal and fetal brain in women treated for depression during pregnancy with selective-serotonin reuptake inhibitors (SSRIs). PAR-20-299 specifically requests translational projects that will enhance the usage of existing drugs for safer and more effective treatment. Barriers to pharmacologic studies to optimize drug treatment in pregnant women include changes in maternal physiology, circulating binding proteins, biologically available drug levels, and drug metabolism. Real-time measurements of fetal drug levels are not currently feasible. Purification of CNSEs from maternal blood allows non- invasive independent evaluation of both the maternal and fetal CNS SSRI targets without significant contamination from each other or non-CNS sources. The goal of this pilot project is to develop a new testing paradigm to rapidly identify women who are poor responders to SSRIs and to investigate the relationship between SSRI treatment, exosome marker levels, and maternal clinical response at a steady state for a given SSRI dose. We will use fetal CNSEs isolated from the same maternal samples to determine if fetuses at risk for neonatal withdrawal symptoms can be identified prior to delivery. This would allow for improved evidence-based management of maternal SSRI treatment in the third trimester based on individualized fetal/neonatal risk and ultimately has the potential to avoid unnecessary medication discontinuation. Completion of this project can change the paradigm for how we assess the safety and efficacy of psychoactive medications in pregnancy.