Breast feeding mothers lose as much as 10% of bone mass during the first six months of a baby's life due to the demand for calcium in the milk. Breastfeeding is a recommended best practice by the American Association of Pediatrics for babies. Use of selective serotonin reuptake inhibitors have been linked with long-term decreased bone mineral density and increase rate of fracture. Though bone density is restored in most women after weaning, without apparent adverse long-term outcomes, our results raise a new concern for the 12% of women who succumb to perinatal depression and the 6% who use selective serotonin reuptake inhibitors (SSRIs) during pregnancy and lactation. Using the pregnant and lactating mouse model we will examine the effect of SSRI use on maternal bone health. Work in our laboratory has shown that serotonin is important for the regulation maternal calcium status during pregnancy and lactation in a rodent model. Furthermore, we have demonstrated that the mechanism by which serotonin controls calcium homeostasis during lactation is through DNA methylation of sonic hedgehog. The novelty of the experiments proposed in this application is that we will perform experiments to test the impact of SSRI treatment during pregnancy and lactation on maternal bone mineral density and the ability of high-dose folic acid supplementation to reverse these results. The results of this experiment are designed to develop a novel intervention for women suffering from perinatal depression that breastfeed to prevent long term reduced bone mineral density. This proposal is highly consistent with the mission of NICHD to ensure “that all children have the chance to achieve their full potential for healthy and productive lives.” We will achieve this by determining the effects of SSRI treatment during pregnancy and lactation on maternal bone health.