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.

项目摘要/摘要 空气污染是一种主要的环境健康威胁，与几种不良健康结果有关 儿童和青少年在内，包括哮喘，肥胖和儿童癌。越来越多的证据表明空气 污染物（包括特定物质（PM））也可能对大脑发育产生负面影响，并增加 心理健康状况不佳。确实，最近的工作表明，暴露于空气污染，特别是PM2.5 （空气直径<2.5μm的PM）与焦虑的患病率和严重程度有关 青年疾病。此外，焦虑症通常在青春期和早发期间开始 发作）与长期不良结局有关，包括更多的慢性疾病和较差的治疗 回复。但是，动画环境风险的基础神经发育机制是 未知。提出的F32将是第一个检验新假设的人，即青少年暴露于较高的假设 最近的PM2.5浓度将杀死不良的延伸召回，下叶降低的激活和更高的焦虑 症状。该项目以先前的研究为基础，证明恐惧扩展和额叶额的受损 功能障碍是焦虑症的神经发育标记，我们最近的初步数据显示 恐惧调节和额骨电路（即海马，海马，腹侧前额叶皮层）在 青少年早期，对环境侮辱敏感（例如，创伤性压力）。此外，新兴 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脑区域是 容易受到PM2.5暴露的影响，尤其是在青少年期间，这是精神病脆弱的时期。这 拟议的研究将招募暴露于最近的PM2.5浓度的青少年，并使用最先进的 高分辨率（0.74 km2）由Brokamp共同开发的时空模型。参与者将完成 为期两天的恐惧扩展功能磁共振成像（fMRI）实验由 赞助商Marusak探究恐惧的调节和额叶额回路。此范式使用虚拟现实耦合 带有心理生理​​记录和神经影像学。这项奖学金研究提供了重要的第一步 旨在确定心理病理环境风险的神经发育机制，并将 告知有针对性的早期干预措施，以阻止处于危险污染的青年中的动画病因。用钥匙 培训环境对脑发育，心理生理学和功能磁共振成像以及神经生物学的影响 小儿动画，该项目非常适合F32机制。该项目得到了一个团队的支持 具有完整专业知识的导师，包括赞助商Marusak和Jovanovic，Ryan，Strawn， 和Brokamp。该培训项目将为Pi Zundel提供扩展所需的关键数据和培训 这项工作纵向，评估暴露于污染的青年中的发展轨迹。它也会准备pi Zundel从事致力于揭示致力于环境的神经发育机制的职业 神经精神病的风险。