# Epigenetic Mechanisms of Depression

> **NIH NIH P50** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2021 · $2,000,000

## Abstract

PROJECT SUMMARY – OVERALL
The objective of this Conte Center is to take maximal advantage of recent advances in chromatin biology, so-
called epigenetics, to fundamentally increase our understanding of the long-lasting abnormalities in the brain
that cause depression. Our work focuses on key limbic brain regions, such as nucleus accumbens and
prefrontal cortex, which have been implicated directly in the control of mood in health and disease. The Center
is composed of four Projects led by Eric Nestler (Mount Sinai), Schahram Akbarian (Mount Sinai), David Allis
(Rockefeller), and Carol Tamminga (UT Southwestern), and two Scientific Cores—the Animal Models Core led
by Venetia Zachariou (Mount Sinai) and Chromatin and Gene Analysis Core led by Li Shen (Mount Sinai). The
PIs, along with several Co-PIs, are leaders in their fields who use their complementary expertise and
approaches to execute a multidisciplinary program of research focused on transcriptional and chromatin
abnormalities both in mouse models of depression and in postmortem brains of depressed humans. A defining
feature of the Center is bidirectional translation, with findings from mice validated in humans, and with
discoveries in humans put back into animal models to study underlying mechanisms. The Center's research is
defined by four themes. First, we study a broad range of epigenetic mechanisms, including histone and DNA
modifications, nucleosome turnover, and the 3D structure of chromatin, which work in concert to control gene
transcription. This involves the use of several next generation sequencing methods and advanced
bioinformatics to analyze the resulting complex datasets. Second, we use this insight to understand how
exposure to stress early in life controls an individual's susceptibility vs. resilience to stress-related disorders for
a lifetime through long-lasting epigenetic mechanisms. Third, we focus on sex differences in this epigenetic
regulation, having defined shared as well as many distinct mechanisms operating in male vs. female brain.
Fourth, these studies are identifying numerous key target genes and molecular pathways that are defining
novel mechanisms underlying depression and other stress-related disorders, which will help drive the field
toward improved treatments and diagnostic tests.

## Key facts

- **NIH application ID:** 10118205
- **Project number:** 5P50MH096890-10
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** ERIC J. NESTLER
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $2,000,000
- **Award type:** 5
- **Project period:** 2012-05-01 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10118205

## Citation

> US National Institutes of Health, RePORTER application 10118205, Epigenetic Mechanisms of Depression (5P50MH096890-10). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10118205. Licensed CC0.

---

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