# Childhood Maltreatment and Disease Risk in Young Adulthood: The Role of HPA Regulation in Adolescence

> **NIH NIH R01** · KAISER FOUNDATION RESEARCH INSTITUTE · 2024 · $629,785

## Abstract

Abstract
Child maltreatment is a significant and costly social issue with over 670,000 documented cases annually. The
effects of maltreatment are wide-ranging and include increased rates of morbidity and mortality from chronic
diseases. To improve the health and mortality of this vulnerable population it is critical to delineate the
pathways through which maltreatment contributes to increased risk for disease and identify opportunities for
prevention. Dysregulation of the body’s physiological stress response systems constitutes a key pathway
through which early maltreatment shapes biological aging processes and risk for subsequent disease. In
addition, recalibration of the stress system during adolescence may mitigate the effects of early trauma on
disease risk. Although the HPA axis in particular has been implicated as a key mechanism linking maltreatment
with disease, these associations have only been tested between any two of these variables (i.e., maltreatment
and HPA axis function, maltreatment and disease, or HPA axis function and disease) using cross-sectional or
retrospective reports of maltreatment. This study will be the first to test this hypothesized mediation model from
maltreatment to disease risk via HPA functioning using a developmental framework from childhood to young
adulthood, incorporating multiple indices of disease risk. Second, the proposed work will be the first to use
innovative new modeling techniques to characterize HPA axis functioning across four timepoints in
adolescence to pinpoint the particular aspects of the stress response and developmental periods of stress
system sensitivity that may lead to disease risk. Finally, this study will move beyond current conceptualizations
of stress system dysfunction by identifying resilient profiles of HPA axis functioning and moderators of HPA
axis recalibration that will provide critical new insights for intervention efforts focused on mitigating the effects
of maltreatment on disease risk. The importance of assessing disease risk in young adulthood is bolstered by
data indicating this period of life as a potential inflection point for long-term disease risk. As such, young
adulthood may be a critical window for prevention and an optimal time to assess modifiable health risks. To
accomplish this, we will leverage a unique prospective longitudinal dataset including youth with documented
maltreatment histories and a comparison group from the same communities (90% minority race/ethnicity). This
exemplary dataset will be augmented with follow-up assessment in young adulthood to capture disease risk.
The findings will provide the first longitudinal evidence of HPA axis as a critical mechanism through which
childhood maltreatment contributes to a lifelong trajectory of disease and whether recalibration of the HPA axis
in adolescence can mitigate the effects of early trauma on disease risk in young adulthood. Identification of
specific moderators of HPA axis recalibration can directl...

## Key facts

- **NIH application ID:** 10848422
- **Project number:** 5R01HD105691-03
- **Recipient organization:** KAISER FOUNDATION RESEARCH INSTITUTE
- **Principal Investigator:** Sonya L Negriff
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $629,785
- **Award type:** 5
- **Project period:** 2022-08-15 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10848422

## Citation

> US National Institutes of Health, RePORTER application 10848422, Childhood Maltreatment and Disease Risk in Young Adulthood: The Role of HPA Regulation in Adolescence (5R01HD105691-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10848422. Licensed CC0.

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