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.

摘要 广大公众已经敏锐地意识到环境毒素对发育中的身体的影响。简言之， 暴露于毒物经常引起体内炎症活性的变化。炎症可以 全身性传播并影响多个器官系统，包括大脑。慢性炎症，即使在低- 年级水平，与消极的心理和认知健康结果有关，包括在 神经回路的发展以及心理症状和障碍的发作和进展。 了解这些毒素的潜在影响，一种令人惊讶的常见但很少研究的环境毒素是 氡。氡是一种自然产生的放射性气体，在家中积聚，对健康造成重大影响。 风险，包括患某些癌症的风险增加，以及对发育敏感组织的损害 和器官的炎症反应。美国环境保护署 把家居氡气浓度的行动上限定为每升4微居里，即相当于吸烟的致癌量10 每天的香烟全国每15户家庭中就有1户预计会有氡浓度， 达到或超过设定的行动限制，使全国各地的大量年轻人长期暴露在高风险环境中， 氡的水平。然而，将氡毒性与神经和认知发育改变联系起来的研究是极其不可靠的。 稀疏。目前的建议旨在通过研究氡的影响来解决这一关键的知识空白 暴露对炎症活动、神经回路以及认知和心理健康功能的影响。我们开创性 初步工作首次显示了慢性氡暴露与特定炎症之间的强有力联系。 活动，再加上赤字的高阶认知和增加抑郁症。我们还 发现证据表明，氡暴露与额顶叶神经网络中的异常神经动力学有关。 这些区域通常与认知和情绪控制有关。在当前的多式联运中， 神经影像学研究，我们将量化家庭氡暴露对炎症过程的影响， 这种炎症是否在与情绪有关的不同神经回路中发挥中介作用， 规则和高阶认知。为此，一组青少年将接受脑磁图检查， (MEG)在一系列旨在评估多个神经系统的任务中， 控制青少年还将完成针对认知和心理健康的评估，并提供血液样本 来检测外周炎症我们的具体目标是：1）确定慢性氡的影响 暴露在涉及情绪和认知控制的神经回路上，以及2）量化中介作用 氡通过炎症过程改变年轻人的神经回路和行为表型。的 这项研究的结果有可能塑造未来的公共卫生政策周围的氡意识 和缓解工作，这是特别真实的，在当地的家庭氡水平是一些 全国最高。