Yen Laboratory

Caring for infants born to 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). It is challenging, if not impossible, to predict which infants will develop severe withdrawal and require medication(s). Through saliva analysis and brain imaging of these infants, Dr. Yen investigates how maternal opioid use exerts sex-specific effects on the developing brain and infant withdrawal. Her research is funded by the NIH K12 BIRCWH (Building Interdisciplinary Research Careers for Women’s Health), K23 (National Institute on Drug Abuse), and Charles H. Hood Foundation grants.

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 male infants with severe withdrawal. The expression of DRD2 also correlated significantly with the caloric intake, 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 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 and feeding dysregulation. Understanding this neurobiological mechanism will provide the basis for developing objective measures to stratify risk and accurately allocate resources for infants with NAS. Ongoing research also examines the impact of maternal opioid use on offspring growth and developmental outcomes.