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

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。简单地说， 暴露在毒物中经常会引起体内炎症活动的变化。炎症可以 系统性传播并影响包括大脑在内的多个器官系统。慢性炎症，即使是低水平的- 年级水平与消极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障碍的发生和发展。 了解这类毒素的潜在影响，一种令人惊讶的常见但很少被研究的环境毒素是 氡气。氡是一种自然产生的放射性气体，积聚在家庭中，对健康构成重大威胁。 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 和器官通过加重的炎症过程。美国环境保护局 将家庭氡浓度的行动限值设定为4pci/L，这相当于吸烟的致癌作用 每天抽一支烟。令人惊讶的是，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上限，使全国各地的大量青年长期暴露在高危状态 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非常多。 稀疏。目前的提案旨在通过审查氡的影响来解决这一关键的知识差距。 暴露在炎症活动、神经回路以及认知和心理健康功能上。我们的开创性工作 初步工作首次显示了慢性氡暴露和特定炎症之间的密切联系。 活动，加上高阶认知障碍和抑郁症状增加。我们还有 发现证据表明，氡暴露与额顶顶叶神经网络的异常神经动力学有关 通常与认知和情绪控制有关的区域。在当前的多式联运 神经成像研究，我们将量化家庭氡暴露对炎症过程的影响，以及 这种炎症是否对与情绪有关的不同神经回路的功能起到了中介作用 调节和更高层次的认知。为此，一组青少年将接受脑磁图检查。 (MEG)在一系列旨在评估服务于认知和情绪的多个神经系统的任务期间 控制力。青少年还将完成针对认知和精神健康的评估，并提供血液样本 以捕捉外周炎症的指标。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 在炎性过程中，氡通过改变年轻人的神经回路和行为表型。这个 这项研究的结果有可能塑造围绕氡意识的公共卫生政策的未来 和缓解努力，这在当地地区尤其如此，那里的家庭氡水平是 是全国最高的。

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.