# Childhood adversity, DNA methylation, and risk for depression: A longitudinal study of protective factors and sensitive periods in development

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2024 · $868,520

## Abstract

Project Summary. Exposure to childhood adversity is one of the strongest risk factors for depression
across the life course, increasing risk by at least twofold. Although these exposures are clearly harmful,
there is substantial variation in how people respond to adversity; not all children who experience early-life
adversity go on to develop mental health problems. This finding raises the question: Are there modifiable
factors early in life that protect against the effects of adversity, contribute to resilient biological processes,
and prevent new onsets of depression? Family- and community-level factors, including maternal social
support, parenting behaviors, grandparent involvement, peer support, and school quality, are established
promotive factors for depression, even among children with a history of adversity. Emerging research
also suggests DNA methylation (DNAm), a well-studied epigenetic modification, may function as a
pathway to explain the biological embedding of these promotive factors. Yet, prior studies in this field
have been small, cross-sectional, and focused mostly on candidate genes. As such, our interdisciplinary
team seeks to considerably advance these insights by identifying the extent to which DNAm mediates, or
partially explains, the effect of these positive life experiences on risk for depression across childhood to
adulthood. We will study these relationships in two birth cohorts: the US-based Fragile Families and
Child Wellbeing Study (FFCWS) and the UK-based Avon Longitudinal Study of Parents and Children
(ALSPAC). Both cohorts are rare in containing repeated measures of positive life experiences, childhood
adversities, DNAm, symptom and/or diagnostic markers of depression risk, and indicators of positive
adaptation. Leveraging our team’s track-record of identifying adversity-linked sensitive periods for DNAm
and depression, we will capitalize on these data to pursue three aims. In all aims, we will model risk (i.e.,
childhood adversity exposure) and positive life experiences simultaneously, which few studies have done
before. In Aim 1, we will characterize the time-dependent effects of positive life experiences on
depression from childhood to adulthood. In Aim 2, we will investigate the time-varying impacts of positive
life experiences on DNAm patterns and trajectories. For Aims 1 and 2, we will use a two-stage structured
life-course modeling approach (SLCMA) our team developed for high-dimensional data. In Aim 3, we will
evaluate the extent to which these DNAm patterns explain the relationship between positive life
experiences and depression using statistical mediation. In sum, this study will: 1) identify modifiable
positive life experiences that shape DNAm and depression patterns, 2) determine if there are sensitive
periods when these experiences are more influential in shaping these outcomes, and 3) generate
insights about promotive and protective biological mechanisms that could lead to new targeted
interventions...

## Key facts

- **NIH application ID:** 10836552
- **Project number:** 5R01MH130442-02
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Erin Cathleen Dunn
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $868,520
- **Award type:** 5
- **Project period:** 2023-05-03 → 2024-06-01

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10836552

## Citation

> US National Institutes of Health, RePORTER application 10836552, Childhood adversity, DNA methylation, and risk for depression: A longitudinal study of protective factors and sensitive periods in development (5R01MH130442-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10836552. Licensed CC0.

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