California Initiative to Advance Precision Medicine Using Precision Medicine to Tackle Impacts of Adverse and Unpredictable Experiences on Children's Neurodevelopment (2021-2024): The SoCal Kids Study
Lead Principal Investigator: Dr. Tallie Z. Baram, University of California, Irvine
Project Summary
This project seeks to:
Background
Adverse childhood experiences (ACEs) have a profound cumulative and negative impact on mental and physical health that remains for a lifetime. The burden of ACEs is not equally distributed, with a heightened risk of exposure among individuals in low socioeconomic and underrepresented communities. Remarkably, some children may be severely affected by early-life adversity, and others may be resilient. Thus, it is important to predict those at risk early in life, so that resources will be allocated to those most in need.
The UCI team, in collaboration with Chapman University, aims to identify the degree to which ACEs influence children’s neurodevelopment and discover a predictive marker for each child for resilience or susceptibility to ACEs.
Many factors govern whether or not a child will be resilient to ACEs, including genetic and environmental factors. Importantly, the effects of ACEs can be mitigated, and the UCI/Chapman University group has shown that predictable signals during a child’s care can buffer them from some of the negative impacts of ACEs. For example, the group documented that keeping consistent family routines amid the stress and chaos imparted by the COVID-19 pandemic helped to protect children’s mental health.
Project Goals
The UCI team aims to:
- Identify, for each child, ACEs that influence the developing brain, especially a recently identified type of adversity (unpredictability) that is most amenable to intervention.
- Discover, for each child, a marker that will predict if they have been impacted by ACEs or are resilient, so that targeted interventions can be delivered to children who need them most.
For the first goal, the UCI team is examining the impact of a novel actionable ACE, unpredictability, on neurodevelopment. In partnership with Children’s Hospital Orange County, they are using data science in >100,000 children to determine the additional neurodevelopmental impact of unpredictable signals from parents and the environment, beyond the predictive value of previously established ACEs.
For the second goal, the UCI team is using a novel Precision Medicine approach to identify a robust epigenetic marker profile of DNA methylation that can distinguish children who have been impacted by cumulative ACEs (and unpredictability) from those who are resilient. This approach will facilitate the delivery of interventions to those in greatest need.
Only some genes (within the DNA code) are active in any cell type at any given time. The regulation of which genes are active is critical, and the complex set of mechanisms that regulate which genes are expressed in our trillions of cells is called epigenetics. While genetics are inherited and remain stable over our lifetime, epigenetics are influenced by our environment, which include ACEs.
A common way for epigenetics to change which genes are active occurs through DNA methylation, an epigenetic modification that turns off certain genes in the cell. Researchers have found evidence of trauma-induced DNA methylation, but because people differ widely in their genetics and epigenetics, it is very difficult to use these data to predict if an individual child is at risk.
The novel, powerful approach of this project is to collect two DNA samples from the same child during development, avoiding the variability in DNA methylation across individuals that can cloud the effects of adversity. The project team believes the changes in methylation over this year will provide valuable information about why individual children are more vulnerable to the effects of stress and adversity in early life.
Team Leaders
Dr. Tallie Z. Baram is the Danette Shepard Professor of Neurological Sciences at UC Irvine. Dr. Baram is a child neurologist and developmental neuroscientist and has focused her efforts on the influence of early life experiences on the developing brain, and those underlying mechanisms. She studies this broad topic in two contexts, including: 1) how early life experiences—including stress and adversity—influence resilience and vulnerability to cognitive and emotional disorders, and 2) how early life seizures, especially those associated with fever, can convert a normal brain into an epileptic one. In the context of the CIAPM, Dr. Baram Directs the UCI Conte Center, in which studies involving both human and experimental rodent models focus on an unrecognized form of early-life adversity: unpredictable signals from parent and environment. The group investigates how this, as well as well-described adversities impact the developing brain, aiming to promote resilience and interventions.
Associate Dean for Research
Chapman University
Dr. Laura Glynn is a Professor of Psychology and an Associate Dean for Research at Chapman University in Orange, California. She also is an elected member of the Academy of Behavioral Medicine Research. Her research focuses on psychobiological origins of mental health, with particular interest in 1) the contributions of maternal stress to adverse birth phenotypes (such as preterm birth and restricted fetal growth), 2) the way in which reproductive history shapes women’s health and development, and 3) the role of prenatal and early life experience in fetal, child, and adolescent cognitive and emotional development.
Professor of Pediatrics and Biomedical Engineering
Director of the Institute for Clinical and Translational Research
UC Irvine
Dr. Dan Cooper is the Associate Vice Chancellor for Clinical and Translational Science and a Professor of Pediatrics at UC Irvine. Since 1978 his research has been focused on the mechanisms that link physical activity with growth and development in babies and healthy children and in those suffering from chronic disease and disability. He has 35 years of continuous NIH funding and leadership roles in complex and multicenter clinical trials.
Dr. Cooper completed a pediatric residency at NYU’s Bellevue Hospital and a pediatric pulmonary fellowship at Columbia University’s College of Physicians and Surgeons Babies Hospital. He earned an MD from UC San Francisco.
Co-Director of LEAD-ABC
UC Irvine, Children's Hospital Orange County
As an academic general pediatrician with the UC Irvine, Department of Pediatrics and Pediatric Exercise and Genomics Research Center (PERC) since 2013, Dr. Candice Taylor Lucas has established strong academic and community partnerships with diverse agencies, addressing the health needs of children and families in Orange County and beyond. She is Co-Director of the UCI Program in Medical Education, Leadership Education to Advance Diversity – African, Black and Caribbean (PRIME LEAD-ABC) and an associate program director for the UCI / Children’s Hospital of Orange County pediatric residency program. Her research interests include how caregiver-child interactions impact health, maternal-child health inequities, and childhood obesity prevention.
Dr. Taylor Lucas earned an MD from the Keck School of Medicine at the University of Southern California and completed a residency in pediatrics at UCLA.
UC Irvine
Dr. Michael Weiss is the Vice President of Population Health for Children’s Hospital Orange County. Over the past three decades, Dr. Weiss has built a pediatric career based on helping children and their families lead the healthiest lives possible. His work has led to groundbreaking programs in Orange County.
Before completing his residency at the Children’s Hospital Los Angeles, Dr. Weiss earned a BA in Biology from the University of Michigan and a DO from The Western University of Health Sciences. He went into private practice in 1989 and spent the next two decades providing primary care to children in Orange County.
Partners, Collaborators, and Supporters
- Allevato Pediatrics
- California State University, San Marcos
- Sabrina Liu, PhD
- Children’s Hosptial Orange County
- Charles Golden, DO, FAAP
- Louis Ehwerhemuepha, PhD
- Mary L. Zupanc, MD
- CHOC Health Center Centrum
- CHOC Health Center Garden Grove
- CHOC Primary Care Network
- Clínica CHOC Para Niños
- First 5 Orange County
- Illumina, Inc.
- Illumination Foundation
- Los Alamitos Pediatrics
- Madison Park Neighborhood Association
- MOMS Orange County
- Orange County Health Care Agency
- Orange Doctors of Kids and Teens
- Pediatric and Adult Medicine
- Premier Pediatrics
- Santa Ana Boys & Girls Club
- Sea View Pediatrics
- Simms/Mann Family Foundation
- Southern Orange County Pediatric Associates
- Syntropy Technologies, LLC
- Total Pediatrics of Orange County
- University of California Irvine
- David Keator, PhD
- Ali Mortazavi, PhD
- Hal Stern, PhD
- Leslie Thompson, PhD
- Pramod Khargonekar, PhD