Cognitive Connie
The HPA Axis & Stress Response
Stress is the body's ancient solution to danger — a cascade of neural and hormonal changes that mobilise energy, sharpen attention, and prepare the organism to fight, flee, or seek allies. The response is orchestrated by two interlocking systems: the fast-acting sympatho-adrenomedullary (SAM) axis, which releases adrenaline and noradrenaline within seconds, and the slower hypothalamic–pituitary–adrenal (HPA) axis, which releases cortisol over minutes to hours.
Key figures
Walter Cannon
Physiologist at Harvard who coined "homeostasis" and "fight-or-flight." Described the sympatho-adrenal response to threat and the concept that stressors disturb homeostatic equilibrium, motivating corrective responses.
Hans Selye
Austrian-Canadian endocrinologist who discovered the General Adaptation Syndrome (1936, 1950) — demonstrating that diverse stressors produce a common nonspecific physiological pattern. Coined the term "stress" in its biomedical sense and identified the adrenal glands as central to the stress response.
Bruce McEwen
Neuroendocrinologist at Rockefeller University who developed the concept of allostatic load and allostasis, quantifying cumulative stress burden. Demonstrated that chronic stress and glucocorticoids cause structural changes in the hippocampus (dendrite retraction, reduced neurogenesis).
Richard Lazarus
Psychologist whose transactional model of stress (with Susan Folkman, 1984) established that stress is not defined by the stressor but by the individual's appraisal of it relative to coping resources. Foundational for cognitive-behavioural stress management interventions.
Shelley Taylor
Health psychologist at UCLA who proposed the tend-and-befriend stress response and established the biological basis of social support as a stress buffer. Major contributor to the field of behavioural medicine.
Robert Ader
Psychologist who founded the field of psychoneuroimmunology with his accidental discovery that classical conditioning can modify immune responses in rats, and subsequent collaboration with immunologist Nicolas Cohen establishing bidirectional nervous-immune communication.
Key concepts
Fight-or-flight response
Walter Cannon's term for the coordinated sympathetic nervous system response to threat: increased heart rate, bronchodilation, peripheral vasoconstriction, glucose mobilisation, and inhibition of digestion. Drives the initial alarm reaction. Complemented by the parasympathetic "rest-and-digest" system during recovery.
SAM axis (Sympatho-adrenomedullary)
The fast-acting stress axis: amygdala/hypothalamus → sympathetic preganglionic neurons → adrenal medulla → adrenaline and noradrenaline released into the bloodstream within seconds. Produces the immediate fight-or-flight response.
HPA axis↗
The hypothalamic–pituitary–adrenal axis: the body's primary endocrine stress system. Hypothalamus releases CRH → anterior pituitary releases ACTH → adrenal cortex releases cortisol. Operates over minutes to hours. Cortisol feeds back to hypothalamus and pituitary to dampen the response.
Cortisol
The primary glucocorticoid released by the adrenal cortex during stress. Mobilises energy (raises blood glucose via gluconeogenesis), suppresses immune and inflammatory responses, modulates memory consolidation, and elevates blood pressure. Chronically elevated cortisol is associated with immunosuppression, metabolic syndrome, hippocampal atrophy, and depression.
General Adaptation Syndrome (GAS)
Selye's (1936) three-stage model of the body's response to prolonged stress: (1) Alarm — initial fight-or-flight activation; (2) Resistance/adaptation — sustained stress hormone elevation; (3) Exhaustion — physiological resources depleted, defences fail, disease vulnerability increases. Demonstrated that diverse stressors produce the same nonspecific physiological response.
Allostatic load
McEwen & Stellar's (1993) concept: the cumulative physiological wear-and-tear on body systems resulting from repeated or chronic activation of stress-response systems. High allostatic load is associated with cardiovascular disease, metabolic syndrome, depression, cognitive decline, and accelerated biological ageing. Accumulates unevenly along socioeconomic gradients.
Cognitive appraisal (Lazarus)
Lazarus and Folkman's transactional model: stress is a transaction between person and environment, mediated by primary appraisal (Is this threatening?) and secondary appraisal (Can I cope?). Stress occurs when perceived demands exceed perceived resources. Changing appraisals (cognitive reappraisal, challenge vs threat framing) can reduce physiological stress responses.
Tend-and-befriend (Taylor)
Shelley Taylor's (2000) proposal that females respond to stress by nurturing offspring ("tending") and seeking social alliances ("befriending"), driven by oxytocin and oestrogen. An evolutionarily plausible alternative to fight-or-flight, particularly for females with dependent offspring. Social support is a key stress buffer in both sexes.
Psychoneuroimmunology
The study of bidirectional communication between the nervous system, endocrine system, and immune system. Demonstrates that psychological stress alters immune parameters: brief acute stress can enhance certain immune functions; chronic stress suppresses T-cell activity, NK cell function, and antibody production. Cohen et al. showed that stress dose-dependently increased susceptibility to experimentally induced colds.
Test your knowledge
Frequently asked questions
Why does chronic stress cause depression?+
Multiple mechanisms link chronic stress to depression: (1) Cortisol — chronically elevated cortisol suppresses hippocampal neurogenesis and causes dendritic retraction in prefrontal cortex; reduced hippocampal volume is one of the most replicated neuroimaging findings in depression. (2) HPA axis dysregulation — depressed patients often show hypercortisolaemia, blunted cortisol awakening response, and failed dexamethasone suppression (HPA negative feedback impairment). (3) Inflammatory pathway — chronic stress activates proinflammatory cytokines (IL-1β, IL-6, TNF-α) that can cross the blood-brain barrier and induce sickness behaviour (fatigue, anhedonia, social withdrawal) resembling depression. (4) Neurotransmitter depletion — sustained stress depletes monoamine systems (noradrenaline, serotonin, dopamine). The inflammation-to-depression pathway explains why inflammatory conditions (arthritis, cardiovascular disease) are associated with elevated depression rates, and why some patients respond to anti-inflammatory treatments.
What is the difference between eustress and distress?+
Selye himself distinguished eustress (positive, motivating stress) from distress (negative, damaging stress). A moderate challenge — a looming deadline, a sporting competition, public speaking for someone who enjoys it — can enhance performance, focus, and wellbeing. This is the Yerkes-Dodson inverted-U: performance improves with increasing arousal up to an optimal point, then declines. Eustress shares the same physiological activation as distress but is appraised as manageable and meaningful. Alia Crum's research shows that beliefs about stress moderate its physiological and health effects: people who believe "stress is enhancing" show better cardiovascular and cognitive responses to stressors than those who believe "stress is harmful." The same objective stressor can be eustress or distress depending on appraisal, resources, and context.
How does social support buffer stress physiologically?+
Social support reduces stress reactivity through multiple mechanisms: (1) Oxytocin — released by social contact, physical touch, and affiliative interaction, it dampens amygdala activity, reduces HPA axis activation, and produces anxiolytic effects. (2) Perceived control — social support increases feelings of coping efficacy, directly reducing appraisal of stressors as threatening. (3) Practical assistance — tangible help reduces objective demands. (4) Emotional validation — feeling understood reduces rumination and negative affect. Physiologically: having a supportive companion present during a stressor reduces heart rate, blood pressure, and cortisol responses. Even viewing a photograph of a significant other, or holding an object belonging to them, can reduce physiological stress reactivity. Conversely, social isolation is associated with chronically elevated allostatic load and premature mortality — with effect sizes comparable to smoking.
Sources
Last reviewed July 2025- 1.
McEwen, B. S. (1998). Stress, adaptation, and disease: Allostasis and allostatic load. Annals of the New York Academy of Sciences, 840(1), 33–44.
+About this source
Introduced the concept of allostatic load and its role in stress-related disease.
- 2.
Sapolsky, R. M. (2004). Why zebras don't get ulcers (3rd ed.). Henry Holt.
+About this source
Accessible and comprehensive account of the biology of stress and its health consequences.
- 3.
Taylor, S. E., Klein, L. C., Lewis, B. P., Gruenewald, T. L., Gurung, R. A. R., & Updegraff, J. A. (2000). Biobehavioral responses to stress in females: Tend-and-befriend, not fight-or-flight. Psychological Review, 107(3), 411–429.
+About this source
Proposed the tend-and-befriend response as an alternative to fight-or-flight, mediated by oxytocin and endogenous opioids.