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.
项目总结
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)
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Margaret Taylor Davis其他文献
Margaret Taylor Davis的其他文献
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{{ 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:
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