# The Impact of Maternal Adversity and Attachment Security on Infant Stress Reactivity: Prenatal Epigenetic Pathways

> **NIH NIH P20** · OSU CENTER FOR HEALTH SCIENCES · 2022 · $236,120

## Abstract

PROJECT SUMMARY/ABSTRACT
Exposure to adverse childhood experiences (ACEs) is linked to deleterious, life-long, and intergenerational
consequences for biobehavioral health. Children of mothers exposed to ACEs show altered stress physiology
and have over 5 times greater odds of developing an emotional or mental disturbance, with risks emerging
early in infancy as dysregulated stress reactivity, poor developmental outcomes, and negative emotionality. A
key biological process underlying the intergenerational transmission of maternal ACEs (mACEs) on offspring is
dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis, driven in part by methylation of glucocorticoid
receptor (GR)-related genes that alter offspring cortisol reactivity. Specifically, mACEs are linked to altered
infant methylation of NR3C1 and FKBP5, though directionality of effects has been inconsistent. In addition to
mACEs, maternal adult attachment orientation (mAttach) is another critical but underexplored environmental
factor implicated in modulation of the physiological stress response and transmission of adversity across
generations. Secure attachment is associated with biobehavioral resilience following childhood adversity, and
moderates the link between ACEs and adverse health outcomes. Attachment orientation is linked to epigenetic
modification of both NR3C1 and FKBP5, and secure attachment is associated with better adaptive functioning
for mothers (regulated stress physiology, fewer physical/mental health problems) and for offspring (secure
attachment, social-emotional development). To date, limited prospective information exists on the functional
implications of GR-related methylation for infant stress reactivity, and no studies have examined methylation of
both NR3C1 and FKBP5 during pregnancy in relation to GR-related methylation and acute stress reactivity in
infants. The proposed study will use a prospective longitudinal design to examine if 1) mACEs and mAttach
predict methylation of maternal and infant glucocorticoid-related genes during pregnancy and postpartum
(Aims 1 and 2); and 2) whether GR-related methylation explains the effects of mACEs and mAttach on
maternal and infant cortisol reactivity (Aim 3). A sample of 100 mothers will be recruited (30-35 weeks
gestation, oversampled for ACEs). mACEs and mAttach will be self-reported at baseline as key predictors and
baseline methylation of NR3C1 and FKBP5 will be measured from saliva. Infant methylation of NR3C1 and
FKBP5 will be measured from saliva at 6-weeks postpartum. Maternal and infant salivary cortisol reactivity to
an acute stressor will be measured at 16-weeks postpartum. The proposed research will help clarify how
adversity is transmitted intergenerationally, linking genes, experiences, and developmental timing to differential
lifelong outcomes and intergenerational health. This work is innovative and a critical step toward our long-term
goal of reducing the harms of ACES by identifying novel, precise...

## Key facts

- **NIH application ID:** 10497045
- **Project number:** 2P20GM109097-06
- **Recipient organization:** OSU CENTER FOR HEALTH SCIENCES
- **Principal Investigator:** Lucia Marie Ciciolla
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $236,120
- **Award type:** 2
- **Project period:** 2016-08-01 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10497045

## Citation

> US National Institutes of Health, RePORTER application 10497045, The Impact of Maternal Adversity and Attachment Security on Infant Stress Reactivity: Prenatal Epigenetic Pathways (2P20GM109097-06). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10497045. Licensed CC0.

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