# In vivo imaging of a neural marker of suicidal behavior in Bipolar Disorder

> **NIH NIH R01** · YALE UNIVERSITY · 2021 · $782,677

## Abstract

PROJECT SUMMARY: Bipolar disorder (BD) is associated with a suicide attempt rate of up to 50% and
completion rate of up to 20%, making prevention and treatment of suicidal behavior in BD one of the most
critical challenges that Psychiatry faces. Women with BD have much higher rate of suicide attempts (SA) than
men, and completion rates are on the rise. The RDoC Suicide Task Force revealed several endophenotypes
that may distinguish attempters versus non-attempters including reward responsiveness and response
inhibition. Further, evidence from fMRI studies indicates that attempters and non-attempters have different
brain responses to reward and inhibition tasks. Alterations have been observed in the dlPFC and OFC, and
these are also the brain regions highly associated with the suicide-related endophenotypes. Unfortunately, the
molecular mechanisms underlying suicidal behavior are not well elucidated and current medications are often
ineffective in reducing the rates of suicide completion. In order to provide more effective treatments for the
highly prevalent suicidal behavior in BD, it is necessary to elucidate the molecular mechanisms that underlie its
associated features, so that they can be targeted with new treatments in men and women with BD. We have
exciting new preliminary evidence supporting the involvement of cortical metabotropic glutamatergic receptors
(mGluR5s) in suicidal behavior. mGluR5 aid in regulation of other glutamatergic receptors, neurotransmission
and synaptic plasticity, which are all critical to healthy mood regulation and cognitive processes. Modulation of
mGluR5 was shown to play a role in reward processing and impulsivity, and mGluR5 associated genes and
proteins have been implicated in suicide specifically. Our novel in vivo data suggest that higher dlPFC and
OFC mGluR5 availability may be a trait marker of suicidal behavior in BD and may therefore aid with the
identification of patients at higher risk for completed suicide. We built upon this knowledge and developed an
innovative multidisciplinary approach to studying this novel mechanism in suicidal behavior. State of the art
positron emission tomography (PET) methods will be used to measure prefrontal cortical mGluR5 levels in
groups of individuals with BD who have and have not attempted suicide in the past. The relationships between
mGluR5 levels and suicide-related endophenotypes will be assessed. Importantly, we will examine the role of
sex in the association between severity of dysregulation in mGluR5 and suicide related endophenotypes, with
the hypothesis that women will exhibit a greater extent of dysregulation in mGluR5 as compared to men.
Further, we hypothesize that individuals in the BD attempt group will have the greatest dysregulation in
mGluR5, and that this will be associated with greatest deficits in the related endophenotypes. These results
may lead to a breakthrough in determining a mechanism that may be important in the pathophysiology of
suicidal ...

## Key facts

- **NIH application ID:** 10076569
- **Project number:** 5R01MH116657-03
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Irina Esterlis
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $782,677
- **Award type:** 5
- **Project period:** 2018-12-01 → 2024-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10076569

## Citation

> US National Institutes of Health, RePORTER application 10076569, In vivo imaging of a neural marker of suicidal behavior in Bipolar Disorder (5R01MH116657-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10076569. Licensed CC0.

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