The Science of Health Disparities Research. Группа авторов

differences in the magnitude of environmental, social, and behavioral influences may be fundamental causes of disparities in disease incidence, progression, and outcomes. Effective interventions—whether social, behavioral, or therapeutic—to eliminate or mitigate health disparities may depend on how thoroughly we understand the biological underpinnings of the contributions of the environment and society (including their influences on behavior) to disease. Developing such interventions will require the combined efforts of interdisciplinary teams, including, for instance, social, behavioral, environmental, and translational scientists. Moreover, understanding the biology of disease and how it may be exacerbated by environmental or behavioral influences will also provide new insights that will assist in identifying population‐specific differences in disease susceptibility across the life course, as well as effective interventions at the biological, behavioral, societal, and environmental levels.

      In this chapter, we discuss the pathways that influence how environmental, social, behavioral, and biological determinants independently and synergistically influence health disparities. We will begin by discussing the concept of allostatic load and how it provides a framework and perspective through which we can understand how environmental, social, behavioral, and biological determinants combine to influence health outcomes and potentially contribute to health disparities. By focusing on studies of social, racial, and ethnic differences in sleep, nutrition, and depression, we will provide examples from the literature that illustrate how such mechanisms converge to influence disparities in health outcomes.

2.2 Allostasis and Allostatic Load

One of the most significant universal biological imperatives is the maintenance of homeostasis. From the Greek homeo, meaning “similar” and stasis, meaning “stand” or “state,” homeostasis refers to the body's ability to maintain internal stability. Humans and mammals have evolved numerous physiological systems to maintain homeostasis (e.g., body temperature, serum electrolytes, blood pressure, and pH). Similarly, from the Greek allo, meaning “other” or “variable,” allostasis refers to change or adaptation to maintain stability and preserve homeostasis, particularly in response to environmental challenges (Figure 2.1a). Allostasis, as initially coined by Sterling and Eyer [2] and popularized by McEwen [3], defines the central role of the brain in stress responses through the neuroendocrine and autonomic nervous system. This system is referred to as the hypothalamic‐pituitary‐adrenal (HPA) axis and, along with elements of the brain governing behavioral and physiological changes in the cardiovascular, metabolic, and autonomic nervous system, is a central component of the global stress response system [4]. Traditionally referred to as the “fight or flight” response, many components of the HPA have adapted to environmental threats or change to promote survival (Figure 2.1b) [5].

Figure 2.1 Schematic representation of the concept of Allostatic Load: (a) Graphic illustration of conceptual linkages between allostasis and environmental stress and chronic disease; (b) Graphic representation of the role and components of allostatic load over the life course illustrating influences of biological embedding, neuronal plasticity, and cumulative “wear and tear” in response to environmental stressors.

      However, persistent or chronic overuse of the stress response systems leads to cumulative “wear and tear,” or cellular, physiological, cognitive, and emotional dysfunction, that eventually becomes maladaptive. Over time, this “weathering,” the disproportionate deterioration as a result of cumulative wear and tear that begins at an earlier age and is patterned by race, can result in disease [6]. The chronic conditions or diseases that result from persistent allostasis are referred to as allostatic load (Figure 2.1b) [3].

      Allostatic load provides a conceptual bridge to understanding how the basic cellular and molecular biology underlying human physiology interacts with behavior and environmental exposures to affect health. Furthermore, it provides a framework to help us understand how certain aspects of human lived experience (e.g., social isolation and racism) and environmental exposure can become “embedded” or “baked in” to influence behavioral patterns and biological events across the life course [3]. The central thesis of allostatic load is that cumulative chronic stress may “get under the skin,” so that past events, occurring as distantly as early childhood or even prenatally, can have persistent effects far into adulthood [7]. These concepts form the foundation that supports how differences in societal experience can be the root cause of disparities in health outcome [8]. The concept of allostatic load enables an exploration of gene‐environment and epigenetic interactions that will ultimately provide insights into intervention.

      In summary, allostasis and the influence of allostatic load occur and accumulate throughout life with consequences that ultimately result in chronic physical, emotional, and cognitive decline [3]. Understanding the forces through which societal, behavioral, and environmental determinants combine with biological susceptibility will be the subject of this chapter.

2.3 The HPA Axis

The HPA axis wields a pervasive influence on health behaviors, including diet, physical activity, and sleep [4, 5]. The paraventricular nucleus (PVN) is a core component of the HPA axis. In response to stress, its neurons produce corticotropin releasing factor (CRF) to stimulate release of pituitary adrenal corticotropic hormone (ACTH), which stimulates production of glucocorticoids (predominantly cortisol) from the adrenal cortex (Figure 2.2) [4, 5]. The net result of the release of circulating cortisol is to mobilize energy through gluconeogenesis, cause peripheral inhibition of glucose and amino acid uptake, and impair or blunt the immune inflammatory response [5]. The result is a rapid increase in blood glucose that will persist under conditions of chronic stress. Cortisol also has significant influence on the central nervous system through feedback inhibition of pituitary ACTH secretion and production of CRF from the PVN, in addition to significant influence on neurogenesis in the amygdala, hippocampus, and mesocorticolimbic regions (Figure 2.2).

Figure 2.2 Schematic presentation of stress pathway outputs and inputs to the hypothalamic‐pituitary‐adrenal (HPA) axis in response to stress. NE, norepinephrine; CRF, corticotropin releasing factor; PVN, paraventricular nucleus; ACTH, adreno‐corticotropin.

      Source: Derived in part from Spencer and Deak [9].

CRF also acts at the level of the locus coeruleus (LC) to potentiate the secretion of norepinephrine (NE), which works in combination with cortisol to enhance consolidation and retrieval of highly emotional events through their combined influence on neurogenesis in the hippocampus, amygdala, and the mesocorticolimbic system (Figure 2.2) [3]. LC‐derived NE also enhances peripheral levels of NE through stimulation of the adrenal medulla, resulting in significant changes in the cardiovascular, pulmonary, renal, gastrointestinal, immune, and hepatic tissues [4, 5].