Early-Life Adversity and Physical and Emotional Health Across the Lifespan: A Neuroimmune Network Hypothesis

Abstract

Children who experience chronic stressors are vulnerable to emotional and physical health problems across the lifespan. This phenomenon raises questions for scientists and clinicians alike. How does adversity get “under the skin” of the developing child? Through what mechanisms does it confer vulnerability to a heterogeneous set of mental and physical illnesses? And how does it instantiate risk across different life stages, engendering vulnerability to conditions that develop shortly after stressor exposure – like depression – and conditions which manifest decades later, like heart disease? Although answers to these questions have started to emerge, research has typically focused on single diseases or organ systems. To understand the plethora of health problems associated with childhood adversity, we argue that the field needs a second generation of research that recognizes multidirectional transactions amongst biological systems. To help facilitate this process, we propose a neuro-immune network hypothesis as a heuristic framework for organizing knowledge from disparate literatures, and as a springboard for generating integrative research. Drawing on existing data, we argue that early-life adversity amplifies crosstalk between peripheral inflammation and neural circuitries subserving threat-, reward-, and executive control-related processes. This crosstalk results in chronic low-grade inflammation, thereby contributing to adiposity, insulin resistance, and other predisease states. In the brain, inflammatory mediators act on cortico-amygdala threat, and cortico-basal ganglia reward, circuitries in a manner that predisposes individuals to self-medicating behaviors like smoking, drug use, and consumption of high-fat diets. Acting in concert with inflammation, these behaviors accelerate the pathogenesis of emotional and physical health problems.

Altered Stress-Induced Regulation of Genes in Monocytes in Adults with a History of Childhood Adversity

“…Under repeated acute or chronic stress, a stress system programmed towards a pro-inflammatory response bias might contribute to a chronic inflammatory environment (Nusslock and Miller, 2015), which is an established vulnerability factor for stressrelated disorders, including major depression (Dantzer et al, 2008;Irwin and Cole, 2011;Miller and Cole, 2012).…”

Childhood and Adolescent Adversity and Cardiometabolic Outcomes: A Scientific Statement From the American Heart Association

“…[91][92][93][94][95] Among people with mental health conditions, childhood adversity, compared with no childhood adversity, results in greater cumulative exposure to mental health symptoms, associated stress, and biological perturbations. [96][97][98] Beyond the direct effects of mental health problems on cardiometabolic outcomes, there are also indirect effects that further exacerbate cardiometabolic risk factors. For example, youth with mood disorders are less likely to achieve recommended levels of physical activity and sleep and more likely to have suboptimal dietary habits, all of which impart cardiometabolic disease risk.…”

Inflammation Effects on Motivation and Motor Activity: Role of Dopamine

“…Subjects with a history of childhood trauma exhibit elevated inflammatory biomarkers and higher rates of depression as adults (Danese et al, 2008;Danese et al, 2007), and a 'biological embedding' or imprinting of stress through inflammatory processes in childhood has been proposed (Danese et al, 2011;Nusslock and Miller, 2015). For instance, subjects with MDD and a history of early life stress responded to psychological stress (the Trier Social Stress Test), with exaggerated circulating IL-6 production and increased DNA binding of nuclear factor-kB in peripheral blood mononuclear cells compared with non-depressed controls (Pace et al, 2006).…”