# Childhood adversity, DNA methylation, and psychopathology symptoms: A longitudinal study of sensitive periods and chrono-epigenetics

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2022 · $670,300

## Abstract

Project Summary. Childhood adversity is a potent risk factor for depression, increasing lifetime risk of
this common and burdensome disorder by at least two-fold. While the association between adversity and
depression is well documented, the mechanisms explaining this relationship are poorly understood. In a
BRAINS R01 award, we made several new discoveries about how childhood adversity could become
biologically embedded to shape depression risk through DNA methylation (DNAm), a major type of
epigenetic modification. We showed that DNAm associations with adversity may not merely be molecular
records of adversity exposure, but rather, possibly function as a biological mediator linking childhood
adversity to depression risk. We also identified potential sensitive periods after birth and in the first five
years of postnatal life when adversity exposure imparted more enduring effects on the epigenome and in
shaping depression risk. However, these analyses were limited to mostly European-ancestry samples of
children with low/moderate adversity exposure and only 2 time points of blood DNAm. In this renewal, we
build on our prior work by exploring these relationships in a population-based longitudinal sample of
children in South Africa, who are part of the Drakenstein Child Health Study (DCHS). Relative to our prior
work and the field of epigenetics at large, the DCHS birth cohort provides an unprecedented opportunity
to study these associations within an established group of more racially/ethnically diverse children, many
of whom have experienced considerable early adversity directly or indirectly through their families own
exposure. We will capitalize on existing, repeated adversity markers collected by the DCHS during early
childhood and derive epigenetic data from stored blood samples collected at ages 1, 3, and 5. With these
rich longitudinal data, we will identify the genetic and social drivers and outcomes of chrono-epigenetics,
a newly coined term to describe the temporal dynamics of epigenetic processes, across the early life
course. In Aim 1, we will characterize the effects of genotype on DNAm levels at specific ages and
DNAm trajectories across time. In Aim 2, we will investigate the role of repeated adversity exposure
measures before age 5 on DNAm patterns using a two-stage structured life-course modeling approach
that our interdisciplinary team developed for high-dimensional epigenetic analyses. In Aim 3, we will use
statistical mediation and causal inference approaches (e.g., Mendelian Randomization) to evaluate the
extent to which these DNAm patterns explain the relationship between adversity timing and children’s
internalizing symptoms at age 8, one of the earliest signs of depression risk. In sum, this renewal project
will identify specific genetic and social factors shaping DNAm patterns, determine the ages when
adversity is most likely to affect this biomarker, and generate biological insights that may lead to new
intervention strate...

## Key facts

- **NIH application ID:** 10444309
- **Project number:** 2R01MH113930-06
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Erin Cathleen Dunn
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $670,300
- **Award type:** 2
- **Project period:** 2017-07-18 → 2027-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10444309

## Citation

> US National Institutes of Health, RePORTER application 10444309, Childhood adversity, DNA methylation, and psychopathology symptoms: A longitudinal study of sensitive periods and chrono-epigenetics (2R01MH113930-06). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10444309. Licensed CC0.

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