In the Journal of the American Medical Association (JAMA), Jack Shonkoff, W. Thomas Boyce and Bruce McEwen discussed a new way of thinking about health promotion and disease prevention.
Adult conditions such as coronary heart disease, stroke, diabetes, and cancerare believed to be causally related to adult behavior and lifestyles only. But recent research indicates that adult chronic disease are linked to processes and experiences occurring decades before, and often as early as intrauterine life.
In the JAMA review the authors outline a new model, which is based on an emerging evidence that the origins of many adult diseases are associated with adversities in the early years of life that establish biological “memories” that weaken physiological systems and produce latent vulnerabilities to problems that occur later, in adult years.
According to the authors, adult conditions and diseases and the causes for poor health “can be embedded biologically during sensitive periods in which the developing brain is more receptive to a variety of environmental signals, whether positive or negative”.
The authors also discuss some new ideas – for example, interventions to reduce significant stress in early childhood may be a more appropriate strategy for preventing adult heart disease than the off-label administration of statins to school-aged children.
The authors argue that exploring the association between early adversity and subsequent health and the identification of biomarkers of toxic stress and its physiological consequences are particularly important.
They conclude that confronting the origins of disparities in physical and mental health early in life may produce greater effects than attempting to modify health-related behaviors or improve access to health care in adulthood. Importantly, effective interventions early in life may have long term effects and can produce “measurable benefits in later educational achievement, economic productivity and responsible citizenship”.
A 2021 special article by W. Thomas Boyce et al., published in Pediatrics stated that adversity, especially early in life, conveys measurable risk to learning and behavior and to the foundations of both mental and physical health. The authors surveyed the independent and interactive roles of genetic variation, environmental context, and developmental timing in light of advances in the biology of adversity and resilience, as well as new discoveries in biomedical research.
This article indicates that the health consequences of both psychosocial stressors and environmental toxicants are often conditioned by genetic variation with respect to individual susceptibility to adversity. The risk of developing adult psychopathology, for example, is related to an interaction between childhood trauma and a functional polymorphism in the FKBP5 gene that controls aspects of glucocorticoid responses to stress.
As per the authors, the interplay between genes and environments takes at least 3 forms. First, gene-environment correlation (rGE) arises when individuals with certain genetic variants choose, alter, or create the social or physical environments in which they live. Second, there are instances in which genetic variations come into play only in the presence of specific environmental conditions (GxE) and, alternatively, some environmental influences become apparent only among individuals carrying a particular genetic variant. A third form of gene-environment interplay includes biological processes in which environmental exposures regulate or calibrate the timing and level of expression of specific sets of genes, resulting in differences in behavior or disease risk.
The well-established connection between early environmental exposures to significant adversity and modifications of the developing brain has been bolstered by growing evidence that other organs are also affected and that these collective changes render a child more susceptible to “second or third hits” by physical or psychosocial stressors later in life.
Stressors produce chemical mediators that trigger adaptive mechanisms in multiple organ systems, termed allostasis, with the goal of maintaining homeostatic balance. Continued exposure to adversity, however, can result in an allostatic load or overload condition, in which neural circuit and cardiometabolic changes have lasting costs in dysfunction and disease.
Children experiencing the stressors of poverty, racism, unsupportive caregiving, and/or maltreatment have increased incidences of inflammation-related obesity and elevated blood pressure. Furthermore, Unsupportive parenting in childhood can similarly lead to increased inflammatory reactivity to major life events, likely through sympathetic activation of inflammatory cytokine production. Increased inflammation is associated with insulin resistance, type 2 diabetes, increased BMI, and altered myelin structure in the developing brain.
This pathogenic cascade of adversity-associated morbidities appears to begin with a chronic proinflammatory state. Major hardships or threats in the family environment, for example, are associated in childhood with upregulation of Nuclear Factor-κ B-responsive genes in peripheral blood mononuclear cells, such as lymphocytes and monocytes, and this effect may persist into adulthood.
Finally, there is evidence that maternal warmth and responsive relationships in adolescence can buffer the adverse effects of chronic immune system activation. As one example, a family-based intervention provided for African-American youth who had grown up under early conditions of poverty produced reductions in inflammation, a decreased incidence of prediabetes, and the promotion of healthy brain development.