Impact of ambient PM2.5 concentrations on fear extinction recall, frontolimbic circuitry, and anxiety in adolescents

环境 PM2.5 浓度对青少年恐惧消退回忆、额边缘回路和焦虑的影响

• 批准号: 10749203
• 负责人: Clara Zundel
• 金额: $ 6.91万
• 依托单位: WAYNE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10749203
• 关键词: Accounting; Adolescence; Adolescent; Adult; Affect; Age; Air Pollutants; Air Pollution; Animals; Anxiety; Anxiety Disorders; Asthma; Biological Markers; Brain; Brain region; Central Nervous System; Child; Childhood; Chronic Disease; Cognitive Therapy; Coupled; Data; Development; Diameter; Early Intervention; Education; Environmental Exposure; Environmental Health; Environmental Impact; Environmental Risk Factor; Etiology; Evidence based treatment; Exhibits; Exposure to; Extinction; Fellowship; Female; Foundations; Fright; Functional Magnetic Resonance Imaging; Functional disorder; Galvanic Skin Response; Graph; Health; Height; Hippocampus; Hour; Human; Impairment; Interruption; Intervention; Learning; Link; Literature; Lung; Malignant Childhood Neoplasm; Measurement; Measures; Mental Health; Mental disorders; Mentors; Modeling; National Institute of Mental Health; Neurobiology; Neurotoxins; Obesity; Outcome; Participant; Particulate Matter; Pathway interactions; Penetration; Physiological; Pollution; Predisposition; Prefrontal Cortex; Prevalence; Psychopathology; Psychophysiology; Recording of previous events; Regulation; Reporting; Research; Research Infrastructure; Resolution; Risk; Role; Severities; Socioeconomic Factors; Structure; Testing; Therapeutic; Toxic Environmental Substances; Training; Training and Infrastructure; Underachievement; Work; Youth; anxiety symptoms; anxiety treatment; blood-brain barrier permeabilization; career; childhood anxiety; cohort; conditioned fear; early adolescence; early onset; experimental study; fine particles; imaging study; interest; learning extinction; negative affect; neural; neural circuit; neurobehavioral; neuroimaging; neuroinflammation; neuropsychiatric disorder; neurotoxic; novel; pre-clinical; recruit; response; spatiotemporal; stem; systematic review; systemic inflammatory response; training project; traumatic stress; treatment of anxiety disorders; treatment response; virtual reality

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.

项目概要/摘要 空气污染是一个主要的环境健康威胁，并与多种不良健康结果相关 越来越多的证据表明，空气对儿童和青少年有影响，包括哮喘、肥胖和儿童癌症。 包括颗粒物 (PM) 在内的污染物也会对大脑发育产生负面影响，并增加患此病的风险 事实上，最近的研究表明，接触空气污染，特别是 PM2.5 会导致心理健康状况不佳。 （空气动力学直径 < 2.5 μm 的 PM）与焦虑的患病率和严重程度相关 此外，焦虑症通常始于青春期和早期发病（相对于成人）。 发病）与不良的长期结果相关，包括更多的慢性疾病和较差的治疗 然而，焦虑环境风险背后的神经发育机制是。 未知。拟议的 F32 将是第一个检验青少年接触更高浓度的新假设的项目。 最近的 PM2.5 浓度会表现出较差的恐惧消退记忆、较低的额边缘激活和较高的焦虑 该项目建立在先前的研究基础上，该研究表明恐惧消退和额叶功能受损。 功能障碍是焦虑症的神经发育标志，我们最近和初步的数据显示 恐惧调节和额边缘回路（即海马体、腹内侧前额叶皮层）在 青春期早期，对环境伤害（例如创伤性应激）敏感。 临床前和人类神经影像学研究表明，与恐惧相关的学习和额叶大脑区域 容易受到 PM2.5 暴露的影响，尤其是在青春期，这是一个精神脆弱的时期。 拟议的研究将招募最近暴露于 PM2.5 浓度的青少年，并使用最先进的技术进行估计 参与者将完成由共同赞助商 Brokamp 开发的高分辨率（0.74 km2）时空模型。 为期两天的恐惧消退功能磁共振成像 (fMRI) 实验由 赞助 Marusak 探索恐惧调节和额边缘电路。该范例使用虚拟现实耦合。 这项奖学金研究提供了重要的第一步。 识别病理环境风险背后的心理神经发育机制，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少年的焦虑病因。 环境对大脑发育的影响、心理生理学和功能磁共振成像以及神经生物学的培训 儿科焦虑症，该项目非常适合 F32 机制 该项目由一个团队支持。 具有互补专业知识的导师，包括赞助商 Marusak 和联合赞助商 Jovanovic、Ryan、Strawn、 该培训项目将为 PI Zundel 提供扩展所需的关键数据和培训。 这项工作是纵向的，评估暴露于污染的青少年的发展轨迹，它还将准备 PI。 Zundel 致力于揭示有助于环境的神经发育机制 神经精神疾病的风险。