A mechanistic investigation of risk factors for opioid use disorder: Examining hippocampal-based context-dependent learning and memory associated with adverse childhood experiences
A mechanistic investigation of risk factors for opioid use disorder: Examining hippocampal-based context-dependent learning and memory associated with adverse childhood experiences
批准号:
10707793
负责人:
Elizabeth Duval
金额:
$70.79万
依托单位国家:
美国
项目类别:
财政年份:
2023
资助国家:
美国
项目状态:
未结题
起止时间:
2023-09-15 至 2028-06-30
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
中文摘要
摘要
英文摘要
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.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Neural mechanisms involved in contextual processing in PTSD
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批准号:10378188
-
项目类别:
-
资助金额:$5.09万
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财政年份:2021
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负责人:Elizabeth Duval
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依托单位:
Neural Mechanisms Involved in Contextual Processing in PTSD
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批准号:9974590
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项目类别:
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资助金额:$17.7万
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财政年份:2017
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负责人:Elizabeth Duval
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依托单位: