# Dysregulation in mGluR5 as a marker of BPD and suicide related endophenotypes

> **NIH NIH K08** · YALE UNIVERSITY · 2022 · $196,628

## Abstract

This mentored clinical scientist research and career development proposal is designed to provide the
candidate advanced training, expert mentoring, and hands-on research experience to facilitate development of
an academic research career. The candidate’s primary goal is to become an independent molecular imaging
researcher studying the neurobiology of suicide in high-risk populations. To achieve that goal, we present a
comprehensive 5-year plan designed to provide rigorous training in four key areas: 1) design and conduct of
PET research in high-risk clinical populations; 2) PET data acquisition and analysis; and 3) advanced statistical
analysis; 4) responsible conduct of research. This proposal will be completed in a diverse, cutting edge
scientific environment (Yale School of Medicine). We further propose conduct of a novel research project using
molecular imaging techniques in a uniquely high-risk population: borderline personality disorder (BPD).
 BPD is a devastating psychiatric condition with alarmingly elevated risk for suicide attempt (up to 75%) and
mortality (up to 10%). Despite BPD’s relatively low prevalence (1-3%), two recent epidemiological studies
reported that more than two thirds of recent suicide attempts occurred in individuals with BPD. Unfortunately,
most of the available treatments are not capable of addressing overall BPD symptom severity or rapidly
reducing suicide risk. Magnetic resonance imaging studies have enhanced our understanding of BPD
pathophysiology, implicating a network of frontal (dlPFC, OFC, ACC), and limbic (amygdala, insula) regions in
BPD symptom presentation. However, investigation of molecular mechanisms subserving BPD
pathophysiology and suicidal behavior is an essential next step to both promote development of novel
treatments and facilitate risk prevention in this population.
 Emerging evidence implicates the metabotropic glutamate 5 receptor (mGluR5) in BPD and suicidal
behavior. mGlur5 plays critical roles in emotion regulation and pain perception which are both central to BPD
pathology and related to suicide risk. Further, genes associated with mGluR5 are linked to suicide attempt and
mortality. Our exciting pilot data in individuals with BPD (n=7) shows higher mGluR5 availability in fronto-llimbic
brain regions linked BPD pathophysiology, with large magnitude differences in those who attempted suicide in
the past. We therefore propose to confirm and extend initial findings by investigating mGluR5 availability in vivo
in BPD using PET and the highly-selective radioligand [18F]FPEB (Aim 1), evaluating the potential role of
mGluR5 as a biomarker for suicide attempt in BPD (Aim 2), and examining the relationship between suicide
and BPD-related behavioral endophenotypes and mGluR5 availability (Aim 3). Results of this study will provide
potentially critical insight into the relationship between this novel molecular target and symptomatology of BPD.
Completion of the proposed training plan and research ...

## Key facts

- **NIH application ID:** 10450146
- **Project number:** 5K08MH117351-05
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Margaret Taylor Davis
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $196,628
- **Award type:** 5
- **Project period:** 2018-08-08 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10450146

## Citation

> US National Institutes of Health, RePORTER application 10450146, Dysregulation in mGluR5 as a marker of BPD and suicide related endophenotypes (5K08MH117351-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10450146. Licensed CC0.

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