# Mechanisms driving sex differences in cognitive outcomes following early life stress

> **NIH NIH R01** · NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC · 2021 · $531,237

## Abstract

ABSTRACT'
!
In the U.S. 16 million children live at or below the poverty line, with as many as 2.5 million children that are
homeless during a given year, and over 700,000 confirmed cases of abuse and/or neglect. Poverty,
displacement, and parental stress, represent some of the most common and potent sources of stress for young
children. Females are at particularly high risk for stress-related pathology, and twice as likely as men to develop
depression or PTSD, conditions that are highly comorbid with cognitive impairments and inflexibility. The goal of
this proposal is to use a mouse model of early life stress (ELS) to identify mechanism underlying sex differences
in risk for early life stress-induced cognitive dysfunction. We will test the novel hypothesis that ELS drives altered
development of parvalbumin-positive interneurons in orbitofrontal cortex (OFC) of female but not male mice, an
effect that underlies stress-associated deficits in rule-reversal learning females. In AIM 1, we will determine the
effects of stress interneuron development in OFC and two control regions. Select cortical populations of
Parvalbumin (PV) interneurons have been heavily implicated in cognitive control, and are significantly affected
by stress. In AIM 2 we will test the hypothesis that inhibiting activity of PV-interneurons in OFC will phenocopy
cognitive deficits observed in female mice reared under ELS conditions. In AIM 3, we will test the impact of ELS
on physiology of PV-positive interneurons in OFC of control and ELS reared male and female mice to determine
if ELS alters the functional development or integration of these cells into the OFC. Through the lens of ELS, the
broad intellectual significance of this work is in its promise for informing the mechanisms driving sex differences
in risk for pathology and the impact of the environment on brain and behavioral development. The questions
addressed here are relevant to a broad scientific audience and also have immediate impact on the development
of translational programming aimed at identifying factors mediating risk and resilience in children and animals
exposed to early adversity.

## Key facts

- **NIH application ID:** 10152672
- **Project number:** 5R01MH115049-05
- **Recipient organization:** NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC
- **Principal Investigator:** Kevin George Bath
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $531,237
- **Award type:** 5
- **Project period:** 2020-10-22 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10152672

## Citation

> US National Institutes of Health, RePORTER application 10152672, Mechanisms driving sex differences in cognitive outcomes following early life stress (5R01MH115049-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10152672. Licensed CC0.

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