# Neurobiology of Suicide: Childhood Adversity, Neuroinflammation and Genomics

> **NIH NIH P50** · NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC · 2021 · $290,339

## Abstract

SUMMARY- PROJECT 1
Childhood adversity is associated with greater risk for adulthood depression (MDD), aggressive traits and
suicide. The overall goal of Project 1 is to define a biological phenotype for suicide and assess the contribution
of reported childhood (before age 16) adversity. In MDD suicides, we find a higher rate of childhood adverse
events. The biological basis of this relationship is mostly unknown, but recent studies, including finds from our
previous Conte Center of thinner prefrontal cortex (PFC) and smaller hippocampus (HC) volume and reduced
BDNF, suggest glucocorticoid excess and impaired trophic effect is a consequence of stress and contributes to
suicide risk. Stress and suicide are also associated with fewer cells and dendritic shrinkage in prefrontal cortex
(PFC) and hippocampus (HC). The thinner PFC and smaller HC volume may constitute a biological risk factor
for stress-related psychopathology. We hypothesize that this neurobiological phenotype may result from
neuroinflammation, environment and epigenetic effects. In the new Conte Center, we aim to determine in the
PFC and HC, whether inflammatory cytokines are increased, whether neurons, glia or both express those
inflammatory markers, and whether the presence of those markers is associated with changes in neuron
number or morphology in 5 groups (n=15 per group) of age- and sex-matched MDD suicides and
nonpsychiatric controls with and without reported childhood adversity (before 15y) and 10 non suicide MDDs,
all with psychological autopsy and brain toxicology. We propose to measure: 1) 62 markers of the
inflammasome in the dorsal PFC (dPFC), ACC and HC; we will estimate total number of neurons and glia in
HC and neuronal and glial density in the dPFC and ACC, with neurons and glia double-labeled with select
cytokines identified from the inflammasome assay; 2) we will count the number of microglia in the HC (at
anterior, mid- and posterior levels) and the density of microglia in dPFC and ACC using microglia specific
markers; and 3) Determine the dendrite length and branching as indices of neuron morphology.
Exploratory aims will: 1) separate the effect of MDD from that of suicide or adversity on neuron and glia
expression of select inflammatory markers comparing the suicide and non-suicide MDD groups; 2) compare
cytokines from brain and blood; TSPO level in postmortem brain and measured by PET; cortical thickness and
HC volume in postmortem brain and measured in vivo by MRI. The proposed studies will provide evidence
whether CA and suicide are associated with a neuroinflammatory response.
!

## Key facts

- **NIH application ID:** 10207363
- **Project number:** 5P50MH090964-09
- **Recipient organization:** NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC
- **Principal Investigator:** MARK D UNDERWOOD
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $290,339
- **Award type:** 5
- **Project period:** 2013-07-19 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10207363

## Citation

> US National Institutes of Health, RePORTER application 10207363, Neurobiology of Suicide: Childhood Adversity, Neuroinflammation and Genomics (5P50MH090964-09). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10207363. Licensed CC0.

---

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