# Preliminary in vivo investigation of the opioid system in borderline personality disorder

> **NIH NIH R21** · YALE UNIVERSITY · 2022 · $209,375

## Abstract

PROJECT SUMMARY
 The goal of this study is to investigate the role of the kappa opioid receptor (KOR) in the symptomatology
of borderline personality disorder (BPD), a condition associated with alarmingly elevated risk for suicide
attempt (up to 75%) and death by suicide (up to 10%). Despite BPD’s relatively low prevalence (1-5%), an
epidemiological study 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 identified structural and
network alterations in BPD symptom presentation and have associated fronto-limbic circuit dysregulation with
an increase in BPD symptom severity. Investigation of molecular mechanisms responsible for BPD symptoms,
and suicide risk specifically is an essential next step to both promote development of novel treatments and
facilitate risk prevention in BPD.
 Emerging evidence implicates KOR in BPD and suicidal behavior. KOR plays critical roles in emotion
regulation, social functioning, and pain perception – all of which are both central to BPD and related to suicide
risk. Postmortem studies have shown an association between KOR and death by suicide. Further, a variety of
studies in both animals and humans have shown that KOR targeted medications can produce antidepressant,
anxiolytic, and even anti-suicidal effects. Importantly, KOR agents’ effect on dopamine is modest relative to
drugs of abuse, reducing concerns about abuse potential. Here, we propose a novel investigation of KOR
availability of in individuals with BPD using positron emission tomography (PET), a brain imaging technique,
and radioligand [11C]EKAP which binds selectively to KOR in the brain (Aim 1). Given the high prevalence of
suicide-related behavior in BPD, we will also evaluate the association between KOR availability, suicide
attempt history, and current suicidal thoughts in BPD (Aim 2). Lastly, we will evaluate the association between
impulsivity, pain tolerance, and self-injury – key endophenotypes of BPD and which are resistant to treatment –
and KOR availability (Aim 3). Results of this study will provide potentially critical insight into the relationship
between this novel molecular target, BPD symptom presentation, and suicidal behavior. Based on findings we
will pursue funding for a larger PET study to test potential non-addictive KOR targeted medications for both
overall BPD symptom reduction, and suicide risk.

## Key facts

- **NIH application ID:** 10317111
- **Project number:** 5R21MH122887-02
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Margaret Taylor Davis
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $209,375
- **Award type:** 5
- **Project period:** 2020-12-15 → 2024-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10317111

## Citation

> US National Institutes of Health, RePORTER application 10317111, Preliminary in vivo investigation of the opioid system in borderline personality disorder (5R21MH122887-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10317111. Licensed CC0.

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