Abstract Child maltreatment is among the most devastating of childhood adversities and increases vulnerability for deleterious outcomes across a number of domains of functioning. However, not all who experience child maltreatment develop problems and those with similar maltreatment experiences may show very different outcomes. Differential biological embedding of maltreatment likely explains this heterogeneity in outcomes. Epigenetics, or the processes that influence gene expression, are crucial to our understanding of how child maltreatment influences later development. DNA methylation (DNAm) is the most well-studied epigenetic mechanism and has been proposed to link early life experiences to alterations in gene expression and mental health symptoms. Only a few studies have used a genome-wide approach to examine these associations and importantly have shown different DNAm patterns for maltreated youth within genes linked with mental health, but did not actually assess outcomes. No longitudinal investigations have tested genome-wide differences in DNAm that emerge after maltreatment and predict the emergence of, or change in, mental health symptoms. A relatively new measure of biological vulnerability, DNAm age, has emerged as an indicator of biological aging that is associated with life stress and has initial support for predicting risk for poor mental health functioning. Although maltreatment is linked with advanced biological aging using other indices (e.g., telomere length), there have been no longitudinal studies testing the effect of maltreatment on DNAm age, nor testing DNAm age as a mediator between maltreatment and later mental health symptoms. To address these gaps, we will use an existing longitudinal sample of maltreated and comparison children (n=454) followed for 10 years with 4 waves of archived samples and a myriad of psychosocial data. This data is optimal to assess the timing of maltreatment effects on genome-wide DNAm, DNAm patterns associated with subsequent mental health, and the potential resolution of problematic DNAm patterns across adolescence (ages 9-23). This is an unprecedented opportunity to capitalize on existing data from a well-designed longitudinal study of maltreated youth with a matched comparison group, which allows us to separate maltreatment effects from other aspects of early life stress and adversity, including neighborhood and socioeconomic factors. This study will contribute important new evidence crucial to our understanding of how maltreatment affects genome-wide epigenetic patterns of vulnerability that result in mental health problems. This will further the development of clinical risk assessment and prevention approaches for maltreated youth which will be of substantial benefit to population health.

R01HD098161

2020-03-01

2025-02-28