Mother Infant Research Institute (MIRI)
Elizabeth Yen, MD, MA, is an Associate Professor of Pediatrics at Tufts University School of Medicine and a Neonatologist at Tufts Medical Center. Caring for infants born of mothers with opioid use disorder, Dr. Yen witnessed the withdrawal signs experienced by these infants, called neonatal abstinence syndrome (NAS) or neonatal opioid withdrawal syndrome (NOWS). Some infants, males more than females, develop severe enough withdrawal and require medication(s). Through saliva analysis and brain imaging of these infants, Dr. Yen investigates how prenatal opioids exert a sex-dependent impact on the developing brain. Her research is funded by NIH K12 BIRCWH (Building Interdisciplinary Research Careers for Women’s Health) grant.
Research Area Focus
Our research focuses on non-invasive salivary gene expression and brain imaging data to elucidate sex-differential roles of the prenatal opioids on the brain, particularly the hypothalamus and reward centers that regulate feeding behavior in infants with NAS. Estimated to cost two billion dollars annually, NAS remains a major public health problem that lacks objective measures due to the largely unknown biological mechanisms underlying the overt withdrawal signs in these infants. Given the proximity of feeding and drug receptors in the brain, we examine the expression of several hypothalamic/reward genes in neonatal saliva to understand a hallmark withdrawal sign, i.e., uncoordinated and excessive sucking (hyperphagia). We found that the expression of a key reward gene, dopamine receptor type 2 (DRD2), was significantly higher in males with severe withdrawal. The expression of DRD2 also correlated significantly with the caloric intake in these males, evidence that DRD2 is linked to hyperphagia, which substitutes for the reward signaling previously provided by the maternal opioids. With multidisciplinary collaborations, we further acquire functional brain imaging to evaluate brain oxygen level dependent (BOLD) signaling changes in response to hunger and satiety signaling in opioid exposed- vs. non-exposed infants. Through these non-invasive platforms, the overarching goal of the Yen Laboratory is to identify which infants with NAS are at risk for severe withdrawal. Understanding this neurobiological mechanism will provide the basis to develop objective measures that will accurately stratify risk and allocate resources for infants with NAS.