# PET Neuroimaging in Vivo in Mood Disorders and Suicidal Behavior

> **NIH NIH P50** · NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC · 2021 · $575,573

## Abstract

SUMMARY - PROJECT 3
Suicide is the 10th leading cause of death in the United States, the 3rd leading cause of death among
individuals age 35-44, and the 2nd leading cause of death among those age 15-34. Completed suicide rates
have risen annually in the United States over the past decade. The molecular pathways contributing to
depression and suicide risk are not well understood, which has hampered novel treatment development. In the
previous period of funding, we used positron emission tomography (PET) to quantify proteins in the serotonin
system, the serotonin transporter and the serotonin 1A receptor, and their association to depression, suicide
attempt history, and neural responses to emotional stimuli. In this renewal application, we propose to expand
our studies to several molecular pathways that appear to be highly relevant to the neurobiology of depression
and suicide. Neuroinflammation is induced by stress, involves activation of microglia in the central nervous
system, and leads to several downstream effects, including impairments in neuroplasticity in the brain as well
as effects on multiple neurotransmitter systems. It may contribute to loss of synapses in brain regions relevant
to the pathophysiology of depression and suicide, including the prefrontal cortex and the hippocampus. Our
group has identified evidence of inflammation in depressed individuals at high risk for suicide from peripheral
blood measurements of inflammatory cytokines, as well as convergent findings of elevated inflammatory
cytokines in the brain through postmortem studies in suicide victims. We now propose to examine
neuroinflammation in vivo in individuals with current major depressive disorder with and without a history of
previous suicide attempt (MDD+SA and MDD-SA), and to compare these groups to healthy volunteers (HV).
We will also gather pilot data to examine a potentially downstream consequence of neuroinflammation, loss of
synaptic density, in a subset of MDD+SA, MDD-SA and HV participants using PET with a novel radiotracer that
serves as a marker or synaptic density. We will follow-up on our findings from the previous funding period by
quantifying the monoamine oxidase A enzyme, which is induced by stress and catabolizes serotonin,
dopamine and norepinephrine. MAO-A has been found to be elevated in MDD and to scale with suicidal
ideation; we will examine its relationship to both depression and suicide attempt history. Lastly, we will
compare PET findings from this project to peripheral measures of inflammation and HPA-axis activity, clinical
symptom profiles, and functional MRI data acquired in other projects of the proposed Conte Center. There are
existing clinical interventions known to target each of the molecular processes being quantified in this proposal,
and great potential for additional treatment development aimed at these targets if we validate their relationship
to depression and suicide risk, which would greatly advance the goal of intervening...

## Key facts

- **NIH application ID:** 10207365
- **Project number:** 5P50MH090964-09
- **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:** 2021
- **Award amount:** $575,573
- **Award type:** 5
- **Project period:** 2013-07-19 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10207365

## Citation

> US National Institutes of Health, RePORTER application 10207365, PET Neuroimaging in Vivo in Mood Disorders and Suicidal Behavior (5P50MH090964-09). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10207365. Licensed CC0.

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