Longitudinal Antecedents of Attention Problems in Very Preterm Children: Role of Epigenetics, Executive Function, and Caregiver Psychological Distress

PROJECT SUMMARY/ABSTRACT This K01 proposal will prepare the candidate for an independent research career studying environmental and biological contributors to child neurodevelopmental trajectories in typically-developing and high-risk populations, with specific expertise in human developmental behavioral epigenetics and clinically-relevant cognitive

phenotypes (e.g., inattention). Research in developmental psychopathology has been successful in identifying risk factors for attention problems across multiple domains, including biological, cognitive, and caregiving factors. However, a missed opportunity is the study of multiple, longitudinal trajectories of risk factors in relation to

trajectories of inattention. Specifically, there is a need to understand whether there are heterogeneous trajectories of inattention in early childhood, particularly during the transition to formal schooling (age 5-7) when increases in inattention are common. Further, understanding how changes in risk factors across early childhood

relate to changes in inattention across the transition to formal schooling could provide critical information regarding modifiable targets and optimal timing for screening and intervening with high-risk children. The proposed study will leverage existing data from two parent grants (R01HD072267; R01HD084515; NOVI study)

focused on neurodevelopmental outcomes in children born very preterm. The current study proposes to test associations between trajectories of biological (i.e., DNA methylation), cognitive (i.e., executive function) and caregiving (i.e., psychological distress) factors and trajectories of child inattention in a sample of children born

very preterm, a group known to be at elevated risk for attention problems. Specific aims are as follows: (1) to

characterize trajectories of inattention in very preterm children; (2) to test the contributions of biological, cognitive, and caregiving factors to trajectories of inattention; and (3) to test how changes in biological, cognitive, and caregiving factors relate to trajectories of inattention. The applicant’s mentorship team will scaffold completion

of the study aims and provide needed training in (1) processing and (2) analysis of high-dimensional, longitudinal epigenetic data, (3) advanced statistical techniques for longitudinal data analysis, and (4) frameworks (e.g., RDOC) for studying child psychopathology. The resources and intellectual environment at the Brown Center for

the Study of Children at Risk, Women and Infant’s Hospital, and Warren Alpert Medical School of Brown University constitute an ideal setting to launch an independent research career. This project will provide preliminary data for a future R01 investigating how trajectories of DNA methylation are established and altered

across development (e.g., as a function of environmental risk factors) as well as grants that follow NOVI children into later childhood. This project is aligned with NIMH strategic priorities given its focus on charting the development of inattention in childhood, identifying risk factors and biomarkers for inattention that could serve

as novel intervention targets, and isolating sensitive periods for interventions aimed at mitigating long-term functional impairment.