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

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 that 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 among biological systems. To help facilitate this process, we propose a neuroimmune 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-related, reward-related, 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.