# in vivo investigation of KOR as a marker of BPD and suicide related endophenotypes

> **NIH NIH R01** · YALE UNIVERSITY · 2023 · $805,619

## 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 (SA; up to 75%) and death by suicide (up to 10%). Despite BPD’s relatively low prevalence (1-5%),
epidemiological research has shown that up to 33% of suicide deaths in the general population are attributable
to BPD. Adding complexity, research suggests that significant sex differences exist in BPD with respect to both
symptoms’ presentation and neurobiology; BPD males have higher suicide risk, but less access to effective
treatment. Despite this, available treatments are largely not capable of addressing overall BPD symptom
severity or rapidly reducing suicide risk. Magnetic resonance imaging (MRI) studies have identified structural
and network alterations in BPD and have associated structural differences and dysregulation in a frontolimbic
circuit of regions with incidence of BPD and increased symptom severity, and suicidal behavior in BPD.
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 impulsivity– 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 antagonists can produce antidepressant, anxiolytic,
and even anti-suicidal effects, though research also suggests men and women may respond differently to such
agents. Importantly, KOR agents’ effect on dopamine is modest relative to drugs of abuse, reducing concerns
about abuse potential. Based on support from novel pilot data using the same techniques, we now propose a
novel investigation of KOR availability in individuals with BPD relative to healthy adults (HA) using positron
emission tomography (PET), a brain imaging technique, and radioligand [11C]EKAP which binds selectively to
KOR in the brain (Aim 1a). We will also evaluate the association between KOR availability and SA history in
BPD (Aim 1b). Next, we will evaluate the association between impulsivity, emotion dysregulation, and BPD
symptom severity – key endophenotypes related to prognosis and suicide risk and resistant to treatment – and
KOR availability in BPD (Aim 2). Finally, we will evaluate sex differences in KOR availability in BPD and HA.
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 bo...

## Key facts

- **NIH application ID:** 10735604
- **Project number:** 1R01MH131720-01A1
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Margaret Taylor Davis
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $805,619
- **Award type:** 1
- **Project period:** 2023-06-20 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10735604

## Citation

> US National Institutes of Health, RePORTER application 10735604, in vivo investigation of KOR as a marker of BPD and suicide related endophenotypes (1R01MH131720-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10735604. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*