Psychological stress in childhood and susceptibility to the chronic diseases of aging: moving toward a model of behavioral and biological mechanisms

Abstract

Among people exposed to major psychological stressors in early life, there are elevated rates of morbidity and mortality from chronic diseases of aging. The most compelling data come from studies of children raised in poverty or maltreated by their parents, who show heightened vulnerability to vascular disease, autoimmune disorders, and premature mortality. These findings raise challenging theoretical questions. How does childhood stress get under the skin, at the molecular level, to affect risk for later diseases? And how does it incubate there, giving rise to diseases several decades later? Here we present a biological embedding model, which attempts to address these questions by synthesizing knowledge across several behavioral and biomedical literatures. This model maintains that childhood stress gets "programmed" into macrophages through epigenetic markings, posttranslational modifications, and tissue remodeling. As a consequence these cells are endowed with proinflammatory tendencies, manifest in exaggerated cytokine responses to challenge and decreased sensitivity to inhibitory hormonal signals. The model goes on to propose that over the life course, these proinflammatory tendencies are exacerbated by behavioral proclivities and hormonal dysregulation, themselves the products of exposure to early stress. Behaviorally, the model posits that childhood stress gives rise to excessive threat vigilance, mistrust of others, poor social relationships, impaired self-regulation, and unhealthy lifestyle choices. Hormonally, early stress confers altered patterns of endocrine and autonomic discharge. This milieu amplifies the proinflammatory environment already instantiated by macrophages. Acting in concert with other exposures and genetic liabilities, the resulting inflammation drives forward pathogenic mechanisms that ultimately foster chronic disease.

Figure 1

The Biological Embedding of Childhood Adversity Model. ACTH = adrenocorticotropic hormone; α7nAChr = α7 subunit of nicotinic acetylcholine receptor; β2AR = β2 adrenergic receptor; GR = glucocorticoid receptor; OR = oxytocin receptor.