Chronic Stress and Disease

The stress response activates two primary systems: the sympathetic-adrenal-medullary (SAM) axis (rapid catecholamine release for fight-or-flight) and the hypothalamic-pituitary-adrenal (HPA) axis (cortisol release for sustained metabolic adaptation). Acute stress is adaptive, but chronic stress produces allostatic overload - the cumulative physiologic burden of repeated adaptation to stressors. Chronic HPA axis activation results in sustained cortisol elevation, which drives visceral adiposity (cortisol upregulates lipoprotein lipase in omental fat), insulin resistance (cortisol impairs GLUT4 translocation), immune dysregulation (suppression of Th1 cellular immunity, promotion of Th2 humoral response, elevated inflammatory cytokines IL-6 and CRP), endothelial dysfunction (accelerated atherosclerosis), hippocampal atrophy (impaired memory and emotional regulation), and bone resorption (osteoporosis). Allostatic load contributes to metabolic syndrome, cardiovascular disease, depression, cognitive decline, and increased susceptibility to infection and autoimmune flares.