Impact of ambient PM2.5 concentrations on fear extinction recall, frontolimbic circuitry, and anxiety in adolescents
Impact of ambient PM2.5 concentrations on fear extinction recall, frontolimbic circuitry, and anxiety in adolescents
批准号:
10749203
负责人:
Clara Zundel
金额:
$6.91万
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
项目状态:
未结题
起止时间:
2023-09-01 至 2026-08-31
关键词:
AccountingAdolescenceAdolescentAdultAffectAgeAir PollutantsAir PollutionAnimalsAnxietyAnxiety DisordersAsthmaBiological MarkersBrainBrain regionCentral Nervous SystemChildChildhoodChronic DiseaseCognitive TherapyCoupledDataDevelopmentDiameterEarly InterventionEducationEnvironmental ExposureEnvironmental HealthEnvironmental ImpactEnvironmental Risk FactorEtiologyEvidence based treatmentExhibitsExposure toExtinctionFellowshipFemaleFoundationsFrightFunctional Magnetic Resonance ImagingFunctional disorderGalvanic Skin ResponseGraphHealthHeightHippocampusHourHumanImpairmentInterruptionInterventionLearningLinkLiteratureLungMalignant Childhood NeoplasmMeasurementMeasuresMental HealthMental disordersMentorsModelingNational Institute of Mental HealthNeurobiologyNeurotoxinsObesityOutcomeParticipantParticulate MatterPathway interactionsPenetrationPhysiologicalPollutionPredispositionPrefrontal CortexPrevalencePsychopathologyPsychophysiologyRecording of previous eventsRegulationReportingResearchResearch InfrastructureResolutionRiskRoleSeveritiesSocioeconomic FactorsStructureTestingTherapeuticToxic Environmental SubstancesTrainingTraining and InfrastructureUnderachievementWorkYouthanxiety symptomsanxiety treatmentblood-brain barrier permeabilizationcareerchildhood anxietycohortconditioned fearearly adolescenceearly onsetexperimental studyfine particlesimaging studyinterestlearning extinctionnegative affectneuralneural circuitneurobehavioralneuroimagingneuroinflammationneuropsychiatric disorderneurotoxicnovelpre-clinicalrecruitresponsespatiotemporalstemsystematic reviewsystemic inflammatory responsetraining projecttraumatic stresstreatment of anxiety disorderstreatment responsevirtual reality
中文摘要
项目总结/文摘
英文摘要
PROJECT SUMMARY/ABSTRACT
Air pollution is a major environmental health threat and is associated with several adverse health outcomes in
children and adolescents including asthma, obesity, and childhood cancer. Growing evidence indicates that air
pollutants, including particulate matter (PM), can also negatively affect brain development and increase risk of
poor mental health outcomes. Indeed, recent work has shown that exposure to air pollution, specifically PM2.5
(PM with an aerodynamic diameter < 2.5 μm) is associated with both the prevalence and severity of anxiety
disorders in youth. Further, anxiety disorders commonly begin during adolescence and early-onset (vs. adult-
onset) is associated with poor long-term outcomes, including more chronic disease and poorer treatment
response. However, the neurodevelopmental mechanisms underlying environmental risk of anxiety are
unknown. The proposed F32 will be the first to test the novel hypothesis that adolescents exposed to higher
recent PM2.5 concentrations will exhibit poor fear extinction recall, lower frontolimbic activation, and higher anxiety
symptoms. This project builds on prior research demonstrating that impaired fear extinction and frontolimbic
dysfunction are neurodevelopmental markers of anxiety disorders, and our recent and preliminary data show
that fear regulation and frontolimbic circuitry (i.e., hippocampus, ventromedial prefrontal cortex) develop during
early adolescence and are sensitive to environmental insults (e.g., traumatic stress). Further, emerging
preclinical and human neuroimaging studies suggest that fear-related learning and frontolimbic brain regions are
susceptible to PM2.5 exposure, particularly during adolescence, a period of psychiatric vulnerability. The
proposed study will recruit adolescents exposed to recent PM2.5 concentrations, estimated using state-of-the-art
high resolution (0.74 km2) spatiotemporal models developed by Co-Sponsor Brokamp. Participants will complete
a two-day fear extinction functional magnetic resonance imaging (fMRI) experiment developed and validated by
Sponsor Marusak to probe fear regulation and frontolimbic circuitry. This paradigm uses virtual reality coupled
with psychophysiological recordings and neuroimaging. This fellowship study provides an important first step
towards identifying neurodevelopmental mechanisms underlying environmental risk of psychopathology, and will
inform targeted early interventions to stem the etiology of anxiety in at-risk pollution-exposed youth. With key
training in environmental impacts on brain development, psychophysiology and fMRI, and the neurobiology of
pediatric anxiety, this project is ideally suited for the F32 mechanism. This project is supported by a team of
mentors with complementary expertise, including Sponsor Marusak and Co-Sponsors Jovanovic, Ryan, Strawn,
and Brokamp. This training project will provide PI Zundel with the critical data and training needed to expand on
this work longitudinally, evaluating developmental trajectories in pollution-exposed youth. It will also prepare PI
Zundel for a career committed to uncovering neurodevelopmental mechanisms contributing to environmental
risk of neuropsychiatric disease.
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