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