# Early Life Stress Effects on Threat Learning

> **NIH NIH R01** · NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC · 2021 · $92,358

## Abstract

Abstract from Parent Project
 Early life stress (ELS) significantly increases the risk for emotional disturbance and affective pathology.
Sixty- four percent of individuals will experience at least one significant stressor in childhood, and this single
adverse event increases the lifetime risk for panic disorder, depression, or anxiety disorders by ~30%.
Experiencing three or more early life stressors doubles the lifetime risk for stress-related pathology. Anxiety
disorders alone cost the American people approximately $42 billion a year, which is approximately one third of
the total $148 billion spent on mental health. Further, according to the World Health Organization, the burden of
disease for neuropsychiatric disorders on the country exceeds that of any other medical condition, even doubling
that of cardiovascular disease, and anxiety disorders pose the greatest threat to mental health worldwide. In the
U.S. nearly 29% of people will develop some form of anxiety disorder in their lifetime. Despite the enormous
burden of stress-related disorders, relatively little is known regarding the neurobiological underpinnings of
pathology development. For many, the roots of later emotional disturbance may lie in altered development and
long-term functioning of cortico-limbic circuits that regulate emotional reactivity and threat evaluation, including
the basolateral amygdala (BLA), the site of threat learning, and the infralimbic (IL) and prelimbic (PL) cortices.
Elegant work in control reared animals have shown that these regions are late maturing and in adult animals
these regions have been shown to be highly sensitive to stress. In recent work, we and other have found that
ELS can drive precocious emergence of some forms of threat-associated learning. However, the extent of ELS
effects on regional maturation, connectivity, and behavioral development are still not known. By investigating
developmental process, we have the potential to identify novel effects of ELS on the maturation and assembly
of this brain circuit, and to understand how altering timing of key neurodevelopmental events may impact the
development of threat assessment and risk for later stress-related pathology. In AIM 1, we will determine the
effects of stress genetic and histological markers of maturation, including connectivity between BLA, IL and PL.
In AIM 2 we will test the hypothesis that ELS alters the developmental profile of threat associated learning and
emergence of anxiety-like behavior. In AIM 3, we will test the specific prediction that ELS drives asymmetrical
cortico-limbic maturation, resulting in a developmental disruption in the ability express threat-associated learning,
with implications for risk for later emotional disturbance. Through the lens of ELS, the broad intellectual
significance of this work is in its promise for informing the mechanisms driving risk for pathology and the impact
of the environment on brain and behavioral development. The questions address...

## Key facts

- **NIH application ID:** 10356242
- **Project number:** 3R01MH115914-04S1
- **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:** $92,358
- **Award type:** 3
- **Project period:** 2021-06-05 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10356242

## Citation

> US National Institutes of Health, RePORTER application 10356242, Early Life Stress Effects on Threat Learning (3R01MH115914-04S1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10356242. Licensed CC0.

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