# Antecedents of Suicidal Behavior Related Neurobiology

> **NIH NIH P50** · NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC · 2020 · $2,655,515

## Abstract

SUMMARY – OVERALL
A 27% increase in US suicides in the past 15 years demands a paradigm shift in prevention driven by research
into causes of suicidal behavior. The Conte Center’s first 4 years of funding identified related brain changes in
suicide and nonfatal suicidal behavior, indicating common causal factors and potential prevention by detecting
future suicide decedents. Key findings include thinner prefrontal cortex and smaller dentate gyrus, partly due to
neuronal loss. We found potential causal abnormalities in HPA axis and inflammasome indices and
deficiencies in trophic systems including the serotonin system (more 5-HT1A autoreceptors) and low BDNF.
These findings link genetics, childhood adversity, epigenetics, mood regulation and cognition to PET and fMRI
abnormalities, stress responses and suicidal behavior. The current proposal seeks to study the neural circuitry
and molecular detail of abnormal stress responses in suicide and nonfatal suicidal behavior, emphasizing
potential etiological and pathogenic roles of the inflammasome, HPA axis and BDNF. Project 1 (Underwood
/Boldrini) uses postmortem brain tissue from suicides with major depressive disorder (MDD) to examine
childhood adversity (psychological autopsy), neuroinflammation and process/synaptic mass in prefrontal
cortex, anterior cingulate cortex and hippocampus, and existing data on genomics (HPA, trophic/apoptotoic,
GABA, Glu, 5-HT, BDNF), neuron and glial number, growth and apoptotic factors, HPA axis and the serotonin
system. Project 2 (Champagne/Hen) applies a maternal separation mouse model to examine effects on
homologous genomics, brain biology and depression, anxiety and aggressive behaviors in a mouse model of
over-expressing 5-HT1A autoreceptors (geneXenviron). Project 3 (Mann) uses PET to quantify a
depression/suicide/aggression/oxidative load-related neurotransmitter index (MAOA), a neuroinflammation
marker (PBR28), & a synaptic marker (UCB-J) and Project 4 (Ochsner) uses fMRI to study mood regulation
and memory in MDD suicide attempters, MDD nonattempters and healthy volunteers. Project 5 (Stanley) will
use ecological momentary assessment and TSST biological stress responses (HPA, adrenergic and
inflammatory) to study emotional and biological stress responses with respect to impulsive or planned suicidal
behavior and reported childhood adversity. Project 6 (Ogden) will use high dimensional brain imaging, genomic
and inflammasome data to develop statistical methods to measure suicidal risk. Findings are compared across
projects in exploratory aims to test a model where childhood adversity leads to greater inflammation, impaired
serotonin and BDNF trophic effects and long-lasting impaired stress responses related to altered brain
morphology and function underlying risk of suicide.!

## Key facts

- **NIH application ID:** 9959463
- **Project number:** 5P50MH090964-08
- **Recipient organization:** NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC
- **Principal Investigator:** Joseph John Mann
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $2,655,515
- **Award type:** 5
- **Project period:** 2013-07-19 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9959463

## Citation

> US National Institutes of Health, RePORTER application 9959463, Antecedents of Suicidal Behavior Related Neurobiology (5P50MH090964-08). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9959463. Licensed CC0.

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