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 - 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.
