# Animal Models of Suicide: Behavior, Neurobiological and Molecular Phenotypes

> **NIH NIH P50** · NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC · 2021 · $157,504

## Abstract

SUMMARY – PROJECT 2 
The experience of childhood adversity in the form of neglect/abuse is a major risk factor for future suicidal 
behavior perhaps via long-term changes in molecular and neurobiological substrates of depression and 
impulsivity/aggression. The effect of early life adversity interacts with genetic vulnerability to confer heightened 
risk of psychopathology and adverse health outcomes. The mechanistic links between childhood adversity, 
genetic risk, molecular/neurobiological pathways, and suicide risk have yet to be established. We propose to 
investigate key hypotheses regarding: 1) whether childhood adversity interacts with 5-HT1A genotype to 
generate heightened risk of suicide behavioral; 2) the relationship between environment and genetic risk for 
suicide on the brain transcriptome and epigenetic variation; 3) the impact on peripheral and brain inflammatory 
pathways of the combined effects of environmental and genetic vulnerability to suicide behavior and the 
relationship of these inflammasome measures to risk behavioral phenotypes. We propose to use mouse 
models as mice are especially well suited to mechanistic studies and transgenic manipulations. Our 
experiments are designed to parallel the molecular, neurobiological and immune outcomes in human studies 
within the center and can thus readily inform the other projects. In Aim 1, we will investigate whether suicide- 
relevant phenotypes in mice (depressive-like, impulsivity/aggression) are heightened through a combination of 
early life adversity (maternal separation) and a targeted genetic manipulation of the 5-HT1A system that results 
in elevated expression of 5-HT1A autoreceptors and subsequent decreased 5-HT levels. Aim 2 determines 
whether early adversity and elevated 5-HT1A autoreceptor levels in the brain result in an altered hippocampal 
and prefrontal cortex transcriptome (using RNA-Seq) and variation in DNA methylation within the BDNF and 
Nr3c1 genes (using bisulfite pyrosequencing). In Aim 3 we will explore the inflammatory consequences of 
genetic and environmental vulnerability to suicide behavior and the relationship of these measures to specific 
suicide behavior phenotypes. To achieve this aim, we will profile cytokine levels within the blood, hippocampus 
and prefrontal cortex of mice that have experienced postnatal maternal separation combined with elevated 
expression of 5-HT1A autoreceptors and assess microglial activation within the brain as a consequence of this 
gene-environment interaction.

## Key facts

- **NIH application ID:** 10207364
- **Project number:** 5P50MH090964-09
- **Recipient organization:** NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC
- **Principal Investigator:** Rene Hen
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $157,504
- **Award type:** 5
- **Project period:** 2013-07-19 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10207364

## Citation

> US National Institutes of Health, RePORTER application 10207364, Animal Models of Suicide: Behavior, Neurobiological and Molecular Phenotypes (5P50MH090964-09). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10207364. Licensed CC0.

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