Developmental Impact of Prenatal Exposure to Methamphetamine and Early Adversity on Children

The rapidly escalating abuse of methamphetamine (METH) in the United States places a sense of urgency on understanding the consequences of METH use during pregnancy for the developing child. To our knowledge, our IDEAL (Infant Development Environment and Lifestyle) study is the only prospective longitudinal NIH study of prenatal METH exposure and child outcome.  204 exposed and 208 matched comparison children were recruited at birth from diverse populations in Iowa, Oklahoma, California and Hawaii where METH use is prevalent.  Children were evaluated at birth to age 7 years for neurobehavioral deficits (NNNS), and acoustic cry parameters, mother-infant attachment, cortisol reactivity, cognitive and motor development, behavior problems, school readiness and executive function.  Also measured were psychosocial risk factors (e.g, poverty, out of home placement, maternal psychiatric status, continued substance abuse in the home) to determine how the effects of prenatal METH exposure are affected for early adversity. There are over 30 publications from the IDEAL study.  Primary Investigators: Barry Lester PhD, Linda LaGasse PhD. 

Epigenetics and Infant Stress Reactivity Related to Variations in Parenting

Merging the fields of epigenetics and human behavior is potentially “game changing” and provides an unprecedented opportunity to discover the molecular basis of human behavior.  Here, we are interested in the role of parenting in altering epigenetic mechanisms that could affect the infants physiological stress reactivity (cortisol) which has been shown to be related to later childhood mental and behavioral disorders. The sample includes infants followed from birth to 4 months of age. DNA of the infant from the placenta and infant neurobehavior (NNNS and cry) were collected at birth. At 4 months, DNA was collected from the infant and the quality of mother infant interaction and infant cortisol stress reactivity were measured.  We expect that results will also inform caregiving-induced signatures on the epigenome that influence infant physiological stress reactivity. Primary Investigators: Barry Lester PhD, Elizabeth Conradt PhD, Carmen Marsit PhD.

Fetal Behavior, Brain, and Stress Response: Ultrasound Markers of Maternal Smoking

Maternal smoking during pregnancy is associated with morbidity and mortality in infants and behavioral deficits in infants and older children. Despite pervasive sanctions against smoking during pregnancy, 13-30% of infants are born exposed. This study provides a novel approach to mothers to observe in real-time, pre-birth neurobehavioral and neural markers of risk from maternal smoking using 2 and 3-dimensional fetal ultrasound. Using an approach pioneered by Dr. Salisbury (2D ultrasound combined with fetal actocardiography), our preliminary work revealed effects of maternal smoking on fetal neurobehavioral deficits and altered stress response during third trimester. However, fetal developmental trajectories leading to third trimester deficits are not known. Further, although structural brain deficits have been proposed as a key candidate mechanism underlying links between maternal smoking and offspring neurobehavioral deficits, no studies have integrated neural and behavioral markers of risk from maternal smoking. Our goals are to determine effects of maternal smoking on: 1) trajectories of fetal neurobehavioral deficits, 2) alterations in fetal stress response, and 3) volume decrements in neural and neuroendocrine structures over pregnancy. We will then test the proposal that trajectories of fetal neuro-behavioral and neural markers of risk predict infant neurobehavioral deficits and stress response, leading to discovery of mechanisms of maternal smoking in real-time during pregnancy, new pre-birth markers of risk that could improve clinical care for pregnant smokers and other high-risk pregnancies. Primary Investigators: Laura Stroud, PhD, Amy Salisbury PhD.

Maternal Lifestyle Study

The Maternal Lifestyle Study (MLS) is the largest of the NIH longitudinal studies of children with prenatal cocaine exposure.  MLS is a multi-site observational study of the long term effects of in-utero exposure to cocaine on child development.  The study included 25 data collection visits (birth to age 16 years) in the birth hospital, study clinic, home, and school. Neurobehavior evaluation (NNNS) and acoustic cry analysis were conducted at the 1-month visit.  Quality of attachment was conducted at 18 and 36 months. Heart rate recording occurred during child activity in the study clinic. Cortisol reactivity during the stressful Trier Task and diurnal cortisol pattern both showed a blunted response in cocaine exposed children, suggesting chronic stress in these children’s lives.  Cocaine exposed children are likely to live in adverse circumstances that may increase the likelihood of behavior problems leading to poor executive function and school achievement, psychopathology, delinquency, early sex and drug use.  MLS has published over 75 publications. Primary Investigators: Barry Lester PhD, Linda LaGasse PhD. 

The MLS data set has been submitted for public access to the National Addiction and HIV Data Archive Program, Inter-University Consortium for Political and Social Research (University of Michigan). The URL is http://dx.doi.org/10.3886/ICPSR34312.v1

Neuroendocrine Correlates of Empathy and Stress Reactivity in Registered Nurses

Understanding the mechanisms of stress is essential to create safe healthcare environments. Intimidating and disruptive behaviors create a stressful and hostile work environment and result in serious adverse outcomes for nurses, and most importantly their patients.  Drawing on evidence from a neuroendocrine framework, individuals with oxytocin receptor gene (OXTR) polymorphism (GG allele) have higher levels of self-reported empathy and lower levels of stress reactivity than individuals with one or two copies of the A allele (AA and AG).  Thus, response to a stressful environment has both a genetic and neurohormonal influence as well as the hostile social environment itself. This is an exploratory feasibility study to examine the relationships among oxytocin receptor gene (OXTR) variation; self-reported empathy; self-reported stress reactivity; and perceived work stress, burnout and violence among acute care registered nurses and mid-level nurse managers.  Recruited nurses received a study packet with instructions to  complete the questionnaires and collect buccal cells using an Isohelix collection kit.  This project provides pilot data for a larger study of the neuroendocrine correlates of empathy and stress reactivity in nurses and interventions to alter behavior and create safe healthcare environments for nurses and their patients. Primary Investigator: Kathe Hawes PhD.

Physiologic Reactivity to Social Stimuli in Children with Autism Spectrum Disorders ASDs

The focus of this research is how psychophysiological markers of arousal measured in children and adults with ASDs differ or are similar to those without ASDs.  These markers include those related to the “fight or flight” response (sympathetic and parasympathetic nervous systems) as well as stress hormones (cortisol).  Our goal is to understand how those with ASDs may react differently based on having some difficulties related to their social and non-social environments. Primary Investigators: Todd Levine MD, Stephen Sheinkopf PhD.