# Fragmented early-life experiences, aberrant circuit maturation, emotional vulnerabilities

> **NIH NIH P50** · UNIVERSITY OF CALIFORNIA-IRVINE · 2020 · $497,759

## Abstract

This trans-disciplinary Center renewal proposal addresses early environmental signals that influence cognitive
and emotional outcomes and the mechanisms by which these signals modulate the development of brain
circuits underlying emotion and cognition. We have identified that patterns of maternal signals profoundly
influence cognitive and emotional development: Specifically, unpredictable and fragmented patterns of
maternal mood and behavior (FRAG) beginning in the fetal period increase the risk for internalizing symptoms
that presage anhedonia and cognitive impairments in infancy through adolescence. Importantly, the effects of
FRAG are additional to those of previously identified influences (e.g. maternal depression, anxiety, sensitivity).
In this revised renewal application we benefit from Reviewer suggestions and capitalize on a cohort of children
developed during the original award period for whom we have an unprecedented pre and postnatal exposure
history, to test the hypothesis that FRAG is a novel form of adversity that influences mental health outcomes
via aberrant maturation of brain circuits. Extending our existing cognitive and emotional assessments and
considering sex and ages at exposure and assessment as important variables, we will emphasize anhedonia,
a novel FRAG outcome identified across species with emerging significance as an important transdiagnostic
dimensional entity in mental illness. We will examine the early manifestation of anhedonia in 3-6 year old
children using a dimensional RDoC approach, determine novel maternal signals that increase risk for its
expression, and identify mechanisms and biomarkers focusing, respectively, on disruption of normal brain
circuit development and epigenetic signatures. Thus, we shall capitalize on our cutting edge neuroimaging,
intra-individual methylomics and novel assessment tools to test the following hypotheses: (1) that early life
exposure to fragmented and unpredictable maternal signals increases risk for anhedonia in 3 to 6-year-old
children. (2) that exposure to a fragmented and unpredictable early life home environment increases the risk of
anhedonia in 3 to 6-year-old children. (3) that early life exposure to fragmented and unpredictable maternal
and environmental signals increases risk for anhedonia in early childhood through the disruption of
pleasure/reward brain circuits and that methylome changes (signatures) in two paired samples from the same
infant will provide predictive biomarkers of this risk.

## Key facts

- **NIH application ID:** 9939736
- **Project number:** 5P50MH096889-07
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** CURT ALAN SANDMAN
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $497,759
- **Award type:** 5
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9939736

## Citation

> US National Institutes of Health, RePORTER application 9939736, Fragmented early-life experiences, aberrant circuit maturation, emotional vulnerabilities (5P50MH096889-07). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9939736. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*