Pathways to mental health: the mediating role of altered cytokines on the relationship between chronic home radon exposure and emotional neural circuitry in developing youths

心理健康之路：细胞因子改变对长期家庭氡暴露与青少年情绪神经回路之间关系的中介作用

• 批准号: 10642381
• 负责人: Brittany Taylor
• 金额: $ 24.45万
• 依托单位: FATHER FLANAGAN'S BOYS' HOME
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-03-10 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10642381
• 关键词: Address; Adolescent; Adolescent Development; Air; Area; Attention; Awareness; Behavioral; Biological Process; Blood specimen; Brain; Carcinogens; Child Development; Chronic; Cigarette; Clinical; Cognition; Cognitive; Country; Coupled; Dangerousness; Data; Development; Developmental Process; Emotional; Emotions; Environment; Environmental Health; Exhibits; Exposure to; Family; Foundations; Future; Gases; Goals; Health; Health Policy; Home; Incidence; Inflammation; Inflammatory; Investigation; Knowledge; Laboratories; Link; Magnetic Resonance Imaging; Magnetoencephalography; Malignant Neoplasms; Malignant neoplasm of lung; Measurement; Measures; Mediating; Mental Health; Mental disorders; National Institute of Environmental Health Sciences; Neurocognitive; Neuropsychology; Organ; Outcome; Outcome Study; Pathway interactions; Pattern; Peripheral; Persons; Process; Psyche structure; Psychometrics; Public Health; Radioactive; Radon; Recommendation; Research; Risk; Role; Severities; Shapes; Smoking; Soil; Source; Strategic Planning; System; Techniques; Tissues; Toxic Environmental Substances; Toxic effect; Toxin; United States; United States Environmental Protection Agency; Well in self; Work; Youth; behavioral phenotyping; biological systems; blood-based biomarker; body system; brain health; carcinogenicity; cognitive ability; cognitive control; cognitive development; cohort; cytokine; depressive symptoms; design; emotion regulation; executive function; indexing; inflammatory marker; innovation; multimodal neuroimaging; multimodality; neural; neural circuit; neurodevelopment; neuroimaging; physical conditioning; psychological symptom; sound; toxicant

Abstract The public at large has grown keenly aware of the effects of environmental toxins on the developing body. Briefly, exposure to toxicants frequently induces changes in inflammatory activity in the body. That inflammation can spread systemically and impact multiple organ systems, including the brain. Chronic inflammation, even at low- grade levels, has been linked to negative mental and cognitive health outcomes, including aberrations in the development of neural circuitry and the onset and progression of psychological symptoms and disorders. Knowing the potential effects of such toxins, one surprisingly common, but rarely studied environmental toxin is radon. Radon is a naturally occurring radioactive gas that accumulates in homes and poses significant health risks, including increased risk of developing certain cancers, and damage to developmentally sensitive tissues and organs through accentuated inflammatory processes. The United States Environmental Protection Agency set the action limit for home radon concentrations at 4 pCi/L, which is the carcinogenic equivalent of smoking 10 cigarettes per day. An astonishing 1 in 15 homes across the country is expected to have radon concentrations at or above the set action limit, leaving a large number of youths across the country chronically exposed to high levels of radon. However, studies linking radon toxicity to altered neural and cognitive development are extremely sparse. The current proposal aims to address this critical gap in knowledge by examining the impact of radon exposure on inflammatory activity, neural circuitry, and cognitive and mental health function. Our groundbreaking preliminary work is the first to show robust links between chronic radon exposure and specific inflammatory activity, coupled with deficits in high order cognition and increased depressive symptomologies. We have also found evidence that radon exposure is associated with aberrant neural dynamics in a network of frontoparietal regions that have been commonly implicated in cognitive and emotional control. In the current multimodal neuroimaging study, we will quantify the impact of home radon exposure on inflammatory processes, and whether such inflammation has a mediating role on functioning in the distinct neural circuits implicated in emotion regulation and higher order cognition. To this end,a cohort of adolescents will undergo magnetoencephalography (MEG) during a battery of tasks designed to assess multiple neural systems serving cognitive and emotional control. Youths will also complete assessments targeting cognitive and mental health, and provide blood samples to capture measures of peripheral inflammation. Our specific aims are to 1) identify the impact of chronic radon exposure on the neural circuitry implicated in emotional and cognitive control, and 2) quantify the mediating role of inflammatory processes through which radon alters neural circuitry and behavioral phenotypes in youths. The outcomes of this study have the potential to shape the future of public health policy surrounding radon awareness and mitigation efforts, and this is especially true in the local region where home radon levels are some of the highest in the nation.

抽象的 整个公众已经敏锐地意识到了环境毒素对发展中心的影响。简要地， 接触毒物经常引起体内炎症活动的变化。炎症可以 系统地传播并影响包括大脑在内的多个器官系统。慢性炎症，即使在低 - 等级水平与负面的心理和认知健康结果有关，包括 神经回路的发展以及心理症状和疾病的发作和发展。 知道这种毒素的潜在影响，一种令人惊讶的常见，但很少研究的环境毒素是 氡。 ra是一种天然存在的放射性气体，可在房屋中积聚并带来重要的健康状况 风险，包括增加某些癌症的风险以及对发育敏感组织的损害 和器官通过强调的炎症过程。美国环境保护局 将家用ra浓度的动作极限设置为4 pci/l，这是吸烟的致癌物质10 每天香烟。预计全国15套房屋中有1个令人惊讶的1个浓度 在设定的行动限制下，全国各地的大量年轻人长期暴露于高位 ra的水平。但是，将ra毒性与改变神经和认知发展的研究极为 疏。当前的建议旨在通过检查ra的影响来解决知识中的这一关键差距 炎症活动，神经回路以及认知和心理健康功能的暴露。我们的开创性 初步工作是第一个显示慢性ra暴露与特定炎症之间牢固联系的工作 活动，以及高阶认知和抑郁症状增加的缺陷。我们也有 发现证据表明ra暴露与额叶网络中的异常神经动力学有关 通常与认知和情感控制有关的地区。在当前的多模式中 神经影像学研究，我们将量化家庭ra暴露对炎症过程的影响，以及 这种炎症是否在与情感有关的独特神经回路中起作用 调节和高阶认知。为此，一群青少年将经历磁脑摄影 （MEG）在一系列旨在评估多个神经系统的任​​务中 控制。年轻人还将完成针对认知和心理健康的评估，并提供血液样本 捕获周围炎症的措施。我们的具体目的是1）确定慢性ra的影响 在涉及情绪和认知控制的神经电路上的暴露，2）量化介导作用 炎症过程通过ra在年轻人中改变神经回路和行为表型的炎症过程。这 这项研究的结果有可能塑造围绕ra的公共卫生政策的未来 和缓解措施，在本地ra是一些的地方，尤其如此 全国最高。