From the Outside In: Biological Mechanisms Linking Social and Environmental Exposures to Chronic Disease and to Health Disparities

The ongoing epidemic of chronic diseases involves a spectrum of clinical entities now understood to represent late manifestations of progressive metabolic dysfunction initiated in early life. These diseases disproportionately affect disadvantaged populations, exacerbating health disparities that persist despite public health efforts.Excessive exposure to stressful psychosocial and environmental forces is 1 factor known to contribute to population-level disparities in at-risk settings. Yet increasing evidence reveals that even a single adverse environmental exposure—especially during very early developmental years—can become literally biologically embedded, inducing long-lasting disease-promoting pathways that amplify responses (e.g., cortisol, immune, inflammatory) to all future adverse stressors, thus enhancing their disease-promoting impacts. The same pathways may also interact with ancestrally linked genetic variants to modify chronic disease risk.We address how, in at-risk populations, environmentally...