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

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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.