# Understanding the Epigenetic Mechanisms Underlying Stress-related Neuropsychiatric Disorders

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2020 · $546,521

## Abstract

Abstract
Epidemiological studies provide mounting evidence supporting that environmental and
experiential influences, such as stressful life events, interact with genetic variations and
compound the risks for neuropsychiatric disorders, such as major depressive disorder (MDD).
MDD afflicts about 6.7% of the United States adults, but treatment options for MDD are limited
and not effective. The objective of this proposal is to define the global epigenetic landscape
associated with stress experience and assess the effect of locus-specific epigenetic changes on
the manifestation of depression-like phenotypes. We propose to first expose both male and
female mice to chronic unpredictable stress paradigms. We will then take a genomic approach
to identify the stress responsive epigenetic code in targeted neuronal cell types in the brain.
Finally, we will modify and apply CRISPR/Cas9 technology to address the causal relationship
between the identified epigenetic code to the expression of depression-like behaviors. With
currently available state-of-the-art technologies and our newly developed, genetically modified
mouse tools, we hope to gain an insight into the epigenetic mechanisms through which stress
interacts with susceptibility genes and confers increased risk to MDD. Our proposed study will
also allow greater understanding of the underlying causes of stress-related neuropsychiatric
disorders and provide the necessary foundation for improved diagnosis and intervention.

## Key facts

- **NIH application ID:** 9849318
- **Project number:** 5R01MH111719-03
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Zhaolan Zhou
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $546,521
- **Award type:** 5
- **Project period:** 2018-01-18 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9849318

## Citation

> US National Institutes of Health, RePORTER application 9849318, Understanding the Epigenetic Mechanisms Underlying Stress-related Neuropsychiatric Disorders (5R01MH111719-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9849318. Licensed CC0.

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