Given that fluctuations in estrogen coincide with PPD symptoms and can be antidepressant when administered as a treatment,7,13–16 we hypothesized that predisposition to PPD risk is due to an altered sensitivity to estrogen-mediated epigenetic changes that act in a cell autonomous manner detectable in the blood. In this study, we performed a multitiered translational approach to predict PPD status in a prospective cohort using DNA methylation from both the human blood and the hippocampus of mice administered E2. We first define genomic regions of E2-mediated epigenetic change in E2-treated mice and investigated the relationship between E2-induced DNA methylation and PPD risk at syntenic regions in humans. Finally, we use E2-induced methylation models generated in the mice to predict PPD status in the humans.
