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

边缘性人格障碍中阿片类药物系统的初步体内研究

基本信息

批准号：
10317111
负责人：
Margaret Taylor Davis
金额：
$ 20.94万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-12-15 至 2024-10-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10317111
关键词：
Address Affect Affective Agonist Amygdaloid structure Analgesics Animals Anterior Anti-Anxiety Agents Antidepressive Agents Attention Autopsy Behavior Binding Borderline Personality Disorder Brain Brain imaging Brain region Chronic Clinical Trials Cognitive Control Groups Depressed mood Development Disease Distress Dopamine Down-Regulation Dynorphins Feeling suicidal Frequencies Functional disorder Funding General Population Goals High Prevalence Human Image Imaging Techniques Impulsivity Individual Injections Intervention Investigation Life Link Low Prevalence Magnetic Resonance Imaging Measurement Mediating Molecular Molecular Target Morbidity - disease rate Naltrexone Opioid Opioid Antagonist Opioid Peptide Pain Pain Threshold Participant Peripheral Pharmaceutical Preparations Pharmacology Play Positron-Emission Tomography Prefrontal Cortex Prevention Psychopathology Recording of previous events Regulation Reporting Resistance Risk Role Savings Scanning Self-Injurious Behavior Severities Social Functioning Stress Suicide Suicide attempt Symptoms System Testing Time Underserved Population Validation Work abuse liability base clinically relevant drug misuse drug of abuse emotion dysregulation emotion regulation endogenous opioids endophenotype epidemiology study experience falls high risk high risk population imaging study in vivo innovation insight interest kappa opioid receptors mu opioid receptors neuroimaging novel opioid mortality opioid use pain perception parametric imaging preclinical study psychiatric symptom radioligand radiotracer receptor-mediated signaling reduce symptoms reducing suicide social stress related disorder suicidal suicidal behavior suicidal morbidity suicidal risk suicide mortality symptom treatment symptomatology targeted agent therapy development treatment risk

项目摘要

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.

项目总结