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:
- 金额:$ 20.94万
- 依托单位:
- 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:
- 关键词:AddressAffectAffectiveAgonistAmygdaloid structureAnalgesicsAnimalsAnteriorAnti-Anxiety AgentsAntidepressive AgentsAttentionAutopsyBehaviorBindingBorderline Personality DisorderBrainBrain imagingBrain regionChronicClinical TrialsCognitiveControl GroupsDepressed moodDevelopmentDiseaseDistressDopamineDown-RegulationDynorphinsFeeling suicidalFrequenciesFunctional disorderFundingGeneral PopulationGoalsHigh PrevalenceHumanImageImaging TechniquesImpulsivityIndividualInjectionsInterventionInvestigationLifeLinkLow PrevalenceMagnetic Resonance ImagingMeasurementMediatingMolecularMolecular TargetMorbidity - disease rateNaltrexoneOpioidOpioid AntagonistOpioid PeptidePainPain ThresholdParticipantPeripheralPharmaceutical PreparationsPharmacologyPlayPositron-Emission TomographyPrefrontal CortexPreventionPsychopathologyRecording of previous eventsRegulationReportingResistanceRiskRoleSavingsScanningSelf-Injurious BehaviorSeveritiesSocial FunctioningStressSuicideSuicide attemptSymptomsSystemTestingTimeUnderserved PopulationValidationWorkabuse liabilitybaseclinically relevantdrug misusedrug of abuseemotion dysregulationemotion regulationendogenous opioidsendophenotypeepidemiology studyexperiencefallshigh riskhigh risk populationimaging studyin vivoinnovationinsightinterestkappa opioid receptorsmu opioid receptorsneuroimagingnovelopioid mortalityopioid usepain perceptionparametric imagingpreclinical studypsychiatric symptomradioligandradiotracerreceptor-mediated signalingreduce symptomsreducing suicidesocialstress related disordersuicidalsuicidal behaviorsuicidal morbiditysuicidal risksuicide mortalitysymptom treatmentsymptomatologytargeted agenttherapy developmenttreatment 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.
项目摘要
本研究的目的是探讨κ阿片受体(KOR)在神经病理学中的作用
边缘型人格障碍(BPD),一种与自杀风险惊人升高相关的疾病,
自杀未遂(高达75%)和自杀死亡(高达10%)。尽管BPD的患病率相对较低(1-5%),
一项流行病学研究报告说,最近三分之二以上的自杀企图发生在患有
波士顿警局不幸的是,大多数现有的治疗方法不能解决整体BPD症状
严重程度或迅速降低自杀风险。磁共振成像研究已经确定了结构和
BPD症状表现的网络改变,并与额叶边缘回路失调相关,
BPD症状严重程度增加。研究导致BPD症状的分子机制,
特别是自杀风险是促进新疗法开发的重要下一步,
促进BPD的风险预防。
新出现的证据表明KOR与BPD和自杀行为有关。KOR在情绪中起着关键作用
调节,社会功能和疼痛感知-所有这些都是BPD的核心,并与自杀有关
风险尸检研究表明KOR与自杀死亡之间存在关联。此外,各种
在动物和人类中的研究已经表明KOR靶向药物可以产生抗抑郁药,
抗焦虑甚至抗自杀的作用重要的是,KOR试剂对多巴胺的影响相对于
药物滥用,减少对滥用可能性的担忧。在这里,我们提出了一个新的调查KOR
使用正电子发射断层扫描(PET),一种脑成像技术,
和放射性配体[11 C]EKAP,其选择性结合脑中的KOR(Aim 1)。鉴于高流行率,
BPD中自杀相关行为,我们还将评估KOR可用性、自杀
BPD中的企图史和当前自杀想法(目标2)。最后,我们将评估
冲动性、疼痛耐受性和自伤--BPD的关键内表型,并且对治疗有抵抗力--
和KOR可用性(目标3)。这项研究的结果将提供潜在的关键洞察的关系
这种新的分子靶点,BPD症状表现和自杀行为之间的联系。根据调查结果,我们
将寻求资金进行更大的PET研究,以测试潜在的非成瘾性KOR靶向药物,
整体BPD症状减轻和自杀风险。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Margaret Taylor Davis其他文献
Margaret Taylor Davis的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Margaret Taylor Davis', 18)}}的其他基金
in vivo investigation of KOR as a marker of BPD and suicide related endophenotypes
KOR 作为 BPD 和自杀相关内表型标志物的体内研究
- 批准号:
10735604 - 财政年份:2023
- 资助金额:
$ 20.94万 - 项目类别:
Dysregulation in mGluR5 as a marker of BPD and suicide related endophenotypes
mGluR5 失调作为 BPD 和自杀相关内表型的标志
- 批准号:
10450146 - 财政年份:2018
- 资助金额:
$ 20.94万 - 项目类别:
Dysregulation in mGluR5 as a marker of BPD and suicide related endophenotypes
mGluR5 失调作为 BPD 和自杀相关内表型的标志
- 批准号:
10224000 - 财政年份:2018
- 资助金额:
$ 20.94万 - 项目类别:
Dysregulation in mGluR5 as a marker of BPD and suicide related endophenotypes
mGluR5 失调作为 BPD 和自杀相关内表型的标志
- 批准号:
9582281 - 财政年份:2018
- 资助金额:
$ 20.94万 - 项目类别:
Dysregulation in mGluR5 as a marker of BPD and suicide related endophenotypes
mGluR5 失调作为 BPD 和自杀相关内表型的标志
- 批准号:
9977813 - 财政年份:2018
- 资助金额:
$ 20.94万 - 项目类别:
Dysregulation in mGluR5 as a marker of BPD and suicide related endophenotypes
mGluR5 失调作为 BPD 和自杀相关内表型的标志
- 批准号:
9756464 - 财政年份:2018
- 资助金额:
$ 20.94万 - 项目类别:
相似海外基金
Affective Virality on Social Media: The Role of Culture and Ideal Affect
社交媒体上的情感病毒传播:文化和理想情感的作用
- 批准号:
2214203 - 财政年份:2022
- 资助金额:
$ 20.94万 - 项目类别:
Standard Grant
'Essaying Affect: the contemporary essay as a place of affective possibility'
“散文情感:当代散文作为情感可能性的场所”
- 批准号:
2438692 - 财政年份:2020
- 资助金额:
$ 20.94万 - 项目类别:
Studentship
Influence of Physical Activity on Daily Positive Affect & Affective Neural Activity in Preschoolers
体力活动对日常积极影响的影响
- 批准号:
10231121 - 财政年份:2018
- 资助金额:
$ 20.94万 - 项目类别:
Influence of Physical Activity on Daily Positive Affect & Affective Neural Activity in Preschoolers
体力活动对日常积极影响的影响
- 批准号:
10475608 - 财政年份:2018
- 资助金额:
$ 20.94万 - 项目类别:
Influence of Physical Activity on Daily Positive Affect & Affective Neural Activity in Preschoolers
体力活动对日常积极影响的影响
- 批准号:
10474838 - 财政年份:2018
- 资助金额:
$ 20.94万 - 项目类别:
Affect- and Psychotechnolog Studies. Emergent Technologies of Affective and Emotional (Self-)Control
影响和心理技术研究。
- 批准号:
279966032 - 财政年份:2015
- 资助金额:
$ 20.94万 - 项目类别:
Scientific Networks
Does minute listeners' head movement affect affective aspects of human spatial hearing perception?
听众的微小头部运动是否会影响人类空间听觉感知的情感方面?
- 批准号:
26540093 - 财政年份:2014
- 资助金额:
$ 20.94万 - 项目类别:
Grant-in-Aid for Challenging Exploratory Research
RI: Small: An Affect-Adaptive Spoken Dialogue System that Responds Based on User Model and Multiple Affective States
RI:Small:基于用户模型和多种情感状态进行响应的情感自适应口语对话系统
- 批准号:
0914615 - 财政年份:2009
- 资助金额:
$ 20.94万 - 项目类别:
Standard Grant
Affective Rendering ? Toward the Realization of Affect Adapted Image Synthesis
情感渲染?
- 批准号:
21300033 - 财政年份:2009
- 资助金额:
$ 20.94万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
A Study by Means of Analysis of Structure of Covariunce, on Factors which Affect Japanese Language Acquisition and Mother Tongue Maintenance of Children from Overseas-an Integral Study of Cognitive Linguistic / Affective / Socio Cultural Factors-
协方差结构分析影响海外儿童日语习得和母语维持的因素研究-认知语言/情感/社会文化因素的综合研究-
- 批准号:
11480051 - 财政年份:1999
- 资助金额:
$ 20.94万 - 项目类别:
Grant-in-Aid for Scientific Research (B)