Acoustic Cry Analyzer for the Diagnosis of Infants Suffering Withdrawal Due To Prenatal Opioid Exposure

The current national opioid epidemic has called for more objective measures of Neonatal Abstinence Syndrome (NAS), thewithdrawal that occurs in newborn infants due to the abrupt discontinuation of prenatal exposure to opiates such as prescription pain medication. Current methods to diagnose NAS rely heavily on cry characteristics (e.g. pitch, amount of crying) but are highly subjective and could lead to the misdiagnosis of NAS and poor or inappropriate treatment. We have developed an automated, computerized Infant Cry Analyzer (ICA) that quantifies the acoustic characteristics of infant cries. This system provides a reliable, objective measure of the acoustical properties of the cry necessary for the accurate diagnosis and clinical management of NAS. Our objective is to quantify the acoustic characteristics of cries of infants with NAS. This proof-of-concept project will enable us to collect data that would attract potential investors in the development of an automated, hand held "iPhone-like" device. Such a device would provide a digital readout indicative of whether or not the infant's cry is symptomatic of NAS. This information can then be used to provide a more accurate diagnosis of NAS, thereby reducing the likelihood of misdiagnosis, and improve the treatment and management of these infants. Primary Investigators: Barry Lester PhD, Stephen Sheinkopf PhD, Harvey Silverman PhD. 

Maternal Smoking: HPA and Epigenetic Pathways to Infant Neurobehavioral Deficits

This study is an intensive investigation of pathways to infant neurobehavioral deficits from maternal smoking. The study involves prospective examination of smokers and controls over pregnancy followed by developmentally-sensitive measures of infant neurobehavior and cortisol reactivity at 1 and 6 months and measurement of novel markers of maternal-placental HPA and epigenetic regulation. The goals are: 1) to characterize effects of maternal smoking on infant neurobehavior and cortisol reactivity at 1 and 6 months, 2) to test the possibility that maternal smoking programs the HPA axis via regulation of maternal glucocorticoids and placental 11β –HSD-2 and that these changes influence infant neurobehavior/cortisol reactivity, 3) to test the hypothesis that maternal-placental HPA regulation is mediated by epigenetic regulation of GR, and 4) to explore sex differences in proposed pathways. Results from the proposed study will elucidate the earliest biomarkers of risk from maternal smoking and may lead to the development of novel therapeutic targets to protect infants whose mothers continue to smoke. Primary Investigators: Laura Stroud PhD, Amy Salisbury PhD.

Preschool Neurobehavior and Prenatal Antidepressant Exposure

Over 400,000 pregnant women and their fetuses experience Major Depressive Disorder (MDD) every year in the United States.   Serotonin/Norepinephrine Reuptake Inhibitors (SRIs), are the most commonly chosen antidepressant medications for MDD during pregnancy.  The original prenatal project focused on prenatal and postnatal development of infants whose mothers had MDD during pregnancy, with and without SRI treatment, compared to non-depressed mothers.  Our early findings suggest that prenatal MDD and SRI exposure are both associated with alterations in sensory-motor development in the fetal period and early infancy. We are now following these children and their families through the preschool years. We hypothesize that the early motor effects of prenatal SRI exposure are related to alterations in fetal serotonin development and that these effects will diminish in exposed children by preschool age.  By comparison, effects attributed to maternal MDD will be longer-lasting.  We are currently examining the role of maternal MDD and prenatal SRI exposure on child sensory-motor integration, gross and fine motor control (kinematics), temperament, behavioral and emotional development, and sleep state with circadian biomarkers (urinary melatonin sulfate levels) related to psychiatric symptoms.  We are also identifying potential epigenetic markers associated with these effects.  The rationale for the proposed research is that once we know how early SRI exposure affects these key areas related to serotonin function, we will be able to identify specific mechanistic pathways, including epigenetic targets and biomarkers, for psychopathology.  The expected outcomes will have a positive impact because they will lead to informed risk-benefit decision-making for pregnant women with MDD and provide new preventive and therapeutic targets for psychopathology in children.  This will further translate into enormous reductions in overall costs due to the social and functional disability that may result from such conditions. Primary Investigators:  Amy Salisbury PhD.

Psychophysiologic Responses in Children and Adults with Autism

Physiological reactivity in response to social stimuli is a strong potential area for developing biomarkers of Autism Spectrum Disorders (ASD).   Biomarkers may be used to improve diagnosis and prediction of functional outcomes. We investigate the activation of the parasympathetic nervous system by using multiple measures of physiologic responses, including heart rate variability, electrodermal responses, and pupilary responses. These measures yield information on individuals’ readiness to engage with the environment, and may be related to social functioning and developmental outcomes in children and adults with ASD. We are exploring how biomarkers may yield insights into the development of early symptoms of autism and whether they may be useful as measures of response to treatment. A goal of our current work in this area is to explore potential differences in physiologic responses during multiple baseline measures and in response to multiple social and nonsocial experiences.  Primary Investigators: Stephen Sheinkopf  PhD, Todd LevineMD, Carolyn McCormick PhD