Project Summary: Postpartum depression (PPD) is highly prevalent in new mothers, with incidence rates estimated to be as high as 1 in 5 mothers, yet we know little about its underlying biology. Several risk factors have been identified, including maternal stress and poor social support in the time around birth. More recently, the neuropeptide oxytocin (OT) has also been implicated in PPD. Variation in circulating levels of OT has been associated with development of PPD and epigenetic modification of the OT receptor gene, OXTR, has been implicated as a risk factor. The proposed experiments seek to model several characteristics of PPD using the prairie vole, including epigenetic regulation of Oxtr, the role of social support before birth and in the postnatal period, and maternal care and anxiety-like behaviors, all in an effort to understand the role OT pathways play in regulating various characteristics associated with PPD. Oxtr DNA methylation and gene expression will be measured at multiple time points across gestation in pregnant females and immediately following birth in new mothers and non-pregnant sister controls to examine the shift in epigenetic regulation of Oxtr across pregnancy. At these same time points, levels of plasma OT will also be examined across pregnancy or soon after birth to characterize changes in the OT peptide in response to pregnancy and birth of offspring. The combination of data on the peptide and epigenetic regulation of its receptor will provide a broad understanding of how the birth experience impacts OT pathways. The persistence of these epigenetic markers will be examined in additional mothers and non-pregnant sister controls either one week after birth or one week after weaning of offspring, after the mother has stopped lactating. This will provide insight into whether these markers on Oxtr are long lasting and if they are dependent on the mother nursing offspring. A lack of social support in the time around childbirth is a known risk factor for PPD in women. Therefore, additional mothers will give birth and rear offspring with or without a social partner present to determine the impact of social support on epigenetic regulation of Oxtr, maternal care of offspring, and maternal anxiety-like and depressive behaviors. The proposed experiments seek to develop a more complete animal model of PPD, one that incorporates both environmental (social support) and genetic (Oxtr epigenetic regulation) components, to gain a better understanding of the development of PPD. This model has the potential to provide valuable information on how pregnancy, birth, and lactation effect functioning of OT pathways to shape the maternal brain.