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
项目摘要/摘要
空气污染是一个主要的环境健康威胁,并与以下几个不利的健康后果有关
儿童和青少年包括哮喘、肥胖症和儿童期癌症。越来越多的证据表明,空气
污染物,包括颗粒物(PM),也会对大脑发育产生负面影响,并增加患心脏病的风险
心理健康状况不佳。事实上,最近的研究表明,暴露在空气污染中,特别是PM2.5
(空气动力学直径<;2.5μm的PM)与焦虑的患病率和严重程度都有关
青年时期的精神障碍。此外,焦虑症通常始于青春期和早发性(与成人相比--
发病)与较差的长期结果有关,包括更多的慢性病和较差的治疗
回应。然而,环境焦虑风险背后的神经发育机制是
未知。提议的F32将是第一个测试这一新假设的人,即青少年接触更高的
最近的PM2.5浓度将表现出较差的恐惧消退回忆,较低的额叶边缘激活,和较高的焦虑
症状。这个项目建立在先前研究的基础上,该研究表明,受损的恐惧消退和额叶边缘
功能障碍是焦虑症的神经发育标志,我们的最新和初步数据显示
恐惧调节和额叶边缘回路(即海马体、前额叶皮质)在
青春期早期,对环境侮辱(如创伤应激)敏感。此外,新兴市场
临床前和人类神经成像研究表明,与恐惧相关的学习和额叶边缘脑区
容易接触PM2.5,特别是在青春期,这是一个精神脆弱的时期。这个
拟议的研究将招募暴露在最近PM2.5浓度下的青少年,使用最先进的估计
由共同赞助商Brokamp开发的高分辨率(0.74平方公里)时空模型。参赛者将完成
一项为期两天的恐惧消退功能磁共振成像(FMRI)实验,由
赞助Marusak探索恐惧调节和前缘回路。该范例使用虚拟现实耦合
有心理生理记录和神经成像。这项团契研究提供了重要的第一步
确定精神病理学环境风险的潜在神经发育机制,并将
告知有针对性的早期干预措施,以遏制高危污染暴露青年焦虑的病因。带钥匙
关于环境对大脑发育的影响、心理生理学和功能磁共振成像的培训,以及
对于儿科焦虑症,这个项目非常适合F32机制。这个项目得到了一支
具有互补专业知识的导师,包括赞助商Marusak和共同赞助商Jovanovic,Ryan,Strawn,
还有布罗坎普。该培训项目将为Pi Zundel提供必要的关键数据和培训,以扩大
这项工作是纵向的,评估了暴露在污染中的年轻人的发展轨迹。它还将准备PI
Zundel致力于揭示神经发育机制对环境的贡献
有患神经精神疾病的风险。
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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