Biological Psychology
Stress Response
HPA axis, cortisol, and how the body's adaptation system breaks under chronic load
The stress response is the coordinated physiological reaction to perceived threat, mediated primarily by the sympathetic-adrenomedullary (SAM) axis on a seconds-to-minutes timescale and the hypothalamic-pituitary-adrenal (HPA) axis on a minutes-to-hours timescale. Walter Cannon described the SAM-mediated "fight or flight" response in 1915. Hans Selye introduced the General Adaptation Syndrome in 1936 and coined the term "stress" itself. Bruce McEwen's 1993 framework of allostasis and allostatic load reframed chronic stress as the cumulative wear from repeated activation, predicting cardiovascular, metabolic, and immune costs that subsequent research has confirmed.
- Fight-or-flight describedWalter Cannon (1915)
- General Adaptation SyndromeHans Selye (1936)
- Allostasis frameworkMcEwen (1993, 1998)
- SAM axis timescaleSeconds to minutes
- HPA axis timescaleMinutes to hours
- Key hormonesAdrenaline, noradrenaline, cortisol
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Why the stress response matters
- Cardiovascular health. Chronic activation drives hypertension and heart disease.
- Mental health. HPA dysregulation appears in depression, PTSD, anxiety disorders.
- Metabolic disease. Cortisol promotes insulin resistance and visceral adiposity.
- Immune function. Acute stress mobilizes immunity; chronic stress suppresses it.
- Aging. Telomere shortening and cellular senescence track allostatic load.
- Performance. Acute stress sharpens focus; chronic stress impairs working memory.
- Therapy targets. Many interventions aim at HPA dysregulation specifically.
Common misconceptions
- All stress is bad. Acute stress mobilizes adaptive performance; chronic stress causes harm.
- Cortisol is the stress hormone. It is one of many; SAM-axis catecholamines act first.
- Anxiety equals stress response. The systems dissociate clinically and physiologically.
- The response is uniform. Tend-and-befriend (Taylor 2000) and freeze responses also occur.
- Fight-or-flight returns immediately. HPA axis fades over hours, not minutes.
- Stress causes ulcers directly. H. pylori is the primary cause; stress is a modifier.
Frequently asked questions
How does the SAM axis work?
A perceived threat triggers the amygdala, which signals the hypothalamus, which activates the sympathetic nervous system. Adrenal medulla releases adrenaline and noradrenaline within seconds. Heart rate and blood pressure rise; airways dilate; digestion suspends; pupils widen; glucose floods the bloodstream. Cannon called this fight-or-flight, and it powers the immediate physiological surge of acute stress. The system shuts down within minutes once threat resolves.
How does the HPA axis work?
The hypothalamus releases corticotropin-releasing hormone (CRH), which stimulates the anterior pituitary to release adrenocorticotropic hormone (ACTH). ACTH travels to the adrenal cortex and triggers cortisol release. Cortisol peaks roughly 20-30 minutes after stressor onset and feeds back to the hypothalamus and pituitary to terminate the response. Cortisol mobilizes energy, suppresses non-essential functions, and tunes immune activity.
What's allostasis?
Sterling and Eyer (1988) coined the term, with McEwen formalizing it. Allostasis describes maintaining stability through change — adjusting setpoints rather than defending fixed homeostatic values. Blood pressure, heart rate, and hormone levels shift to meet predicted demand. Allostatic load is the cumulative physiological cost of repeated allostatic adjustment. Chronic activation produces measurable damage to brain, heart, and metabolic systems.
What does chronic stress do?
Documented effects include hippocampal atrophy (Sapolsky's primate work), prefrontal dysfunction, amygdala hypertrophy, immune dysregulation, insulin resistance, hypertension, and accelerated cellular aging via telomere shortening (Epel et al., 2004). Cortisol receptors downregulate, producing glucocorticoid resistance. The combined load underwrites elevated cardiovascular and metabolic disease risk in chronically stressed populations.
How does the response differ from anxiety?
The stress response is a physiological reaction; anxiety is the emotional and cognitive experience that often accompanies it. Stress responses occur in animals without subjective anxiety. Anxiety persists even when no current physiological stress response is firing. The two systems share neural substrates (amygdala, prefrontal cortex) but dissociate clinically — patients can have flat physiology with high subjective anxiety, and vice versa.
What's the diurnal cortisol rhythm?
Cortisol peaks 30-45 minutes after waking — the cortisol awakening response (CAR) — and declines through the day to a nighttime nadir. Healthy variability includes morning peak, mid-afternoon plateau, and evening decline. Flattened rhythms (low morning peak, elevated evening) appear in chronic stress, depression, and PTSD. Saliva sampling at multiple daily timepoints is the standard non-invasive measure.
What interventions reduce allostatic load?
Aerobic exercise, sufficient sleep, social support, and behavioral therapies for insomnia and depression have the strongest evidence. Mindfulness meditation shows reductions in cortisol reactivity and CAR (Pascoe et al. 2017). Pharmacological options (beta-blockers, SSRIs) reduce specific components. The strongest predictor of recovery is removing or restructuring the chronic stressor itself, not damping the downstream physiology.