A mechanistic investigation of risk factors for opioid use disorder: Examining hippocampal-based context-dependent learning and memory associated with adverse childhood experiences
阿片类药物使用障碍危险因素的机制研究:检查与不良童年经历相关的基于海马的情境依赖学习和记忆
基本信息
- 批准号:10707793
- 负责人:
- 金额:$ 70.79万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-09-15 至 2028-06-30
- 项目状态:未结题
- 来源:
- 关键词:AdultAmygdaloid structureAnimalsAnxietyBehavioralBrainBuprenorphineCessation of lifeChronic DiseaseClinicalCognitiveComplexControl GroupsCross-Sectional StudiesCuesDangerousnessDetectionDevelopmentDisparateEmotionalFoundationsFunctional disorderFutureHippocampusHormonesIndividualInjuryInvestigationLearningLinkLongitudinal StudiesMeasuresMedicalMemoryMental DepressionMental disordersModelingModernizationNeurocognitiveNeurocognitive DeficitNeuronsNeurosciencesOpioid agonistOutcomeOverdosePain DisorderPanthera leoPathway interactionsPatient Self-ReportPatientsPerformancePersonsPopulationPost-Traumatic Stress DisordersPrefrontal CortexPreventionProcessPublic HealthRewardsRiskRisk FactorsSamplingSeveritiesShapesStressStructureSubstance Use DisorderTestingTraumaWorkadverse childhood eventsanxiety symptomsassociated symptombrain basedchronic paincommon symptomcomorbidityconditioned fearcostdepressive symptomsdesigndisorder riskemotional functioningexperiencemortalityneuralopioid epidemicopioid misuseopioid overdoseopioid useopioid use disorderprescription opioidprogramspsychiatric symptomrecruitremediationrisk sharingstress related disordersubstance usesurgical paintoolway finding
项目摘要
Abstract
Opioid medications have been widely prescribed in efforts to control medical and surgical pain, but opioid use
disorder (OUD) has become a serious, prevalent, and costly public health problem. Identifying risk factors for
the development of OUD after prescribed opioid use could help reduce serious injury and mortality-related
outcomes, like overdose. Hippocampal (Hpc)-circuit based context processing is an important neuro-cognitive
process associated with OUD. Evidence for context processing deficits is seen in psychiatric, substance use,
and chronic pain populations. One major predictor of adult OUD that is also linked to context processing is
adverse childhood experiences (ACEs). ACEs predict high OUD rates and are associated with complex co-
morbidity (e.g., chronic pain, psychiatric conditions, other substance use disorders) that complicates treatment
for OUD. ACEs also compromise Hpc function through detrimental effects of stress hormones on Hpc neurons.
Thus, ACEs may lead to Hpc circuitry dysfunction and context processing deficits, providing a shared pathway
to chronic pain, prescribed opioid use, and OUD development. This Katz R01 will utilize the PI’s expertise in
neurocognitive mechanisms of trauma to provide the first direct examination of a mechanistic pathway of risk
for OUD that involves links between ACEs and context processing deficits. We will examine 75 adults with
OUD taking the prescription opioid agonist buprenorphine (BUP) and compare them to two control groups: 75
adults without OUD taking BUP and 75 adults without OUD and not taking BUP, in a cross-sectional study. We
will use a well-validated context processing paradigm to interrogate Hpc structure and function and behavioral
performance. Validated self-report and objective measures of opioid misuse, OUD, and ACEs will be used to
examine links between ACEs, context processing, and OUD. Our specific aims include: 1) identifying Hpc-
circuit based context processing deficits in OUD, independent of opioid agonist effects; 2) establishing
links between ACEs, context processing, and OUD severity; and 3) exploring how common symptom
domains are associated with ACEs, context processing, and OUD. The findings from this project will lead
to longitudinal work with the potential to trace a mechanistic pathway that helps explain co-morbidities between
chronic pain, stress-related disorders, and OUD development after prescribed opioid use. This may ultimately
open new doors to discovery of prevention and treatment paradigms that will identify those at risk when opioids
are prescribed (high ACEs, poor context processing), and ultimately shape neuroscience-informed ways to
remediate functional deficits even after they have developed.
抽象的
阿片类药物已被广泛规定以控制医学和手术疼痛,但使用阿片类药物
疾病(OUD)已成为严重,普遍且昂贵的公共卫生问题。确定风险因素
开处方使用阿片类药物后的OUD的发展可能有助于减少严重的伤害和死亡率有关
结果,例如过量。海马(HPC)基于电路的上下文处理是重要的神经认知
与Oud相关的过程。上下文处理缺陷的证据在精神病,使用物质中可以看出
和慢性疼痛人群。与上下文处理有关的成人OUD的一个主要预测指标是
不利的童年经历(ACE)。 ACE可以预测高速率,并与复杂的共同共同
发病率(例如,慢性疼痛,精神病,其他物质使用障碍)使治疗复杂化
对于Oud。 ACE还通过应力角对HPC神经元的有害影响损害了HPC功能。
这可能会导致HPC电路功能障碍和上下文处理缺陷,提供共享途径
慢性疼痛,处方阿片类药物的使用和OUD发育。这个Katz R01将利用Pi的专业知识
创伤的神经认知机制,以首次直接检查风险的机械途径
对于涉及ACE和上下文处理缺陷之间的链接的OUD。我们将检查75名成年人
OUD服用处方阿片类动力学丁丙诺啡(BUP),并将它们与两个对照组进行比较:75
在一项横断面的研究中,没有Oud的成年人,没有OUD和75名没有OUD且不服用BUP的成年人。我们
将使用验证良好的上下文处理范例来询问HPC结构,功能和行为
表现。经过验证的自我报告和阿片类遗物,OUD和ACE的客观度量将用于
检查ACE,上下文处理和OUD之间的链接。我们的具体目的包括:1)确定HPC-
基于电路的上下文处理防御源,与阿片类药物激动剂效应无关; 2)建立
ACE,上下文处理和OUD严重性之间的联系; 3)探索常见症状
域与ACE,上下文处理和OUD相关联。该项目的发现将领导
进行纵向工作,以追踪有助于解释合并症的机械途径的潜力
处方使用阿片类药物后,慢性疼痛,与压力相关的疾病和OUD发育。这可能最终
打开发现预防和治疗范式的新门,这些范例将确定阿片类药物时有危险的人
开处方(高昂的王牌,不良的上下文处理),并最终塑造神经科学知识的方法
补救功能缺陷即使在开发之后。
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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Elizabeth Duval其他文献
Elizabeth Duval的其他文献
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{{ truncateString('Elizabeth Duval', 18)}}的其他基金
Neural mechanisms involved in contextual processing in PTSD
参与 PTSD 情境处理的神经机制
- 批准号:
10378188 - 财政年份:2021
- 资助金额:
$ 70.79万 - 项目类别:
Neural Mechanisms Involved in Contextual Processing in PTSD
参与 PTSD 情境处理的神经机制
- 批准号:
9974590 - 财政年份:2017
- 资助金额:
$ 70.79万 - 项目类别:
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