Inflammatory biomarkers and oral microbiome alterations in depression and anxiety disorders: a systematic review.

Each individual’s unique environment and lived experiences play an essential role in shaping cognitive neurodevelopment. Previous work has identified numerous environmental factors that relate to neurodevelopment and cognition, including physical and chemical exposures (e.g. lead poisoning () or air pollution (; )), psychosocial experiences (e.g. caregiver relationship (, ) or adverse life events ()), and external environments (e.g. socioeconomic resources () or cultural influences ()). Most studies to date have examined associations with just one or a few environmental factors at a time. However, it is increasingly accepted that these features often co-occur non-randomly and likely have additive and interactive effects on the developing brain. For example, living in a high poverty neighborhood is associated with greater risk of exposure to air pollutants and traumatic experiences, which in turn are associated with individual differences in cognitive, psychiatric, and neurodevelopmental outcomes (, , ). Consequently, there are increasing efforts to more comprehensively measure each individual’s complex, multidimensional environment, referred to collectively as an individual’s “exposome”. Efforts to characterize the exposome have begun to uncover important associations between large sets of co-occurring environmental features and individual differences in neurodevelopmental outcomes, with potential to ultimately inform policies and interventions that support healthy neurocognitive development (). The concept of the “exposome” was first introduced as a complement to the genome in epidemiological studies (), emphasizing the importance of capturing the totality of co-occurring environmental exposures in addition to genetic influences on physical health. The exposome approach builds upon a long history of prior research examining how specific aspects of early life environments relate to physical and mental health outcomes, including efforts to uncover mechanistic links between adverse experiences and risk for psychiatric illness. Recently, definitions of the exposome have expanded to include psychosocial and sociocultural factors in addition to physical and chemical exposures throughout an individual’s lifetime (). The exposome provides a complementary perspective that improves predictive power by more comprehensively capturing the additive and interactive effects of co-occurring environmental features which are not fully captured by measures of cumulative risk and severity and that may collectively shape health outcomes through complex and interacting pathways. Thus, while previous efforts have made great progress in characterizing mechanistic associations between specific features of the environment and specific neurocognitive outcomes, the broader exposome approach can provide complementary information about how the collective effects of one’s multidimensional environment may shape cognitive neurodevelopment more broadly (). Emerging work has already begun to leverage large-scale datasets, such as the Adolescent Brain Cognitive Development℠ Study (ABCD StudyⓇ) (), to investigate associations between the exposome and the spatial organization of functional brain networks (), cognitive outcomes (, , ), and mental health (, ). For example, a multidimensional exposome score reflecting lower socioeconomic status (SES) is associated with poorer cognitive performance and worse mental and physical health (). In addition, including multidimensional environmental exposures improves brain-based predictions of cognitive performance () in held-out data beyond what can be gained by including single environmental features such as household income or neighborhood deprivation indices alone. Prior studies have leveraged bifactor analysis to quantify both a single general exposome factor and several sub-factors that capture specific dimensions of the enrivonment (, ). The general exposome factor uncovered using this bifactor approach in the ABCD Study primarily captures co-occurring environmental features related to socio-economic inequality and is strongly associated with symptoms of psychopathology (), cognitive performance (), and individual differences in the spatial organization of functional brain networks () in youth.