The neurobiology of stress operates primarily through two major neuroendocrine axes: the fast-acting Sympathomedullary (SAM) Axis and the slower, sustained Hypothalamic-Pituitary-Adrenal (HPA) Axis. When a stressor is perceived by higher cortical structures and processed by the amygdala, the hypothalamus triggers the sympathetic nervous system to stimulate the adrenal medulla, releasing catecholamines (epinephrine and norepinephrine) which elevate heart rate, blood pressure, and metabolic rate.
Simultaneously, the paraventricular nucleus of the hypothalamus releases Corticotropin-Releasing Hormone (CRH), stimulating the anterior pituitary gland to secrete Adrenocorticotropic Hormone (ACTH) into the bloodstream. ACTH acts upon the adrenal cortex, prompting the synthesis and release of glucocorticoids, notably cortisol. Cortisol mobilizes energy resources (gluconeogenesis) and suppresses non-essential functions such as immune, reproductive, and digestive processes. Chronic elevation of cortisol leads to hippocampal atrophy, dendritic retraction in the prefrontal cortex, and downregulation of glucocorticoid receptors.