# Neurogenomics of Vulnerability and Resilience to Mental Health Syndromes in Response to Extreme Life Events

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2020 · $409,701

## Abstract

The emergence of high-throughput and cost-efficient sequencing technologies has led to dramatic recent
progress in identifying genetic correlates of mental health syndromes. Despite this progress, the underlying
biological mechanisms remain poorly understood. Critical challenges include determining which variants are
causally related to disease etiology, how this variation is associated with variation in social behavior and
cognition, and how this variation interacts with the environment to produce dysfunction. The standard approach
to address these challenges is to study small animal models like mice and flies, but such models are limited by
their simple behavioral and cognitive repertoire and potential differences in the underlying neural circuitry,
compared with humans. A promising alternative is to define the multi-omic architecture and neuroanatomy
associated with complex social behavior in nonhuman primates, which share core neural and genetic pathways
with humans adapted to social life.
The goal of the proposed research is to identify how the brain processes social experiences to produce a
greater understanding of vulnerability and resilience to life events that ultimately affect health and well-being.
Specifically, we will quantitatively define social support and social vulnerability in the free-ranging rhesus
macaque population of Cayo Santiago Island (Puerto Rico) and will assess the associations between these
factors and the multi-omic architecture and neuroanatomy of the primate brain. We will do so under typical
environmental conditions but will also take advantage of the occurrence of an extreme environmental event, a
major hurricane, to evaluate social resilience in multiple conditions.
First, we will describe the neurogenomic and regulatory landscape in the primate social brain and its
associated anatomical implications under baseline chronic stress conditions. We will generate region specific
transcriptomes and epigenomes for brain areas associated with social information processing and implicated in
mental health genetic models. We will combine these genomic data with detailed measures of structural
connectivity and receptor densities collected using brain imaging and histology techniques. The combination of
these approaches will help us develop a fully-realized biological model that recapitulates the genetic and
environmental contributions to social phenotypes as well as their molecular, structural, and functional
correlates. Finally, we will delineate how social support buffers the impact of a traumatic life event and the
resulting severe and sudden stressful experiences of Hurricane Maria and its aftermath. Development of this
type of animal model will permit us to more effectively target interventions that directly impact the neural
circuits mediating behaviors impaired in a variety of mental health syndromes.

## Key facts

- **NIH application ID:** 10018111
- **Project number:** 5R01MH118203-02
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** MICHAEL L PLATT
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $409,701
- **Award type:** 5
- **Project period:** 2019-09-13 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10018111

## Citation

> US National Institutes of Health, RePORTER application 10018111, Neurogenomics of Vulnerability and Resilience to Mental Health Syndromes in Response to Extreme Life Events (5R01MH118203-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10018111. Licensed CC0.

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