The HPA Axis & Stress Response

Hans Selye (1936) proposed that any sufficiently intense or prolonged stressor produces the same three-stage physiological response: (1) Alarm reaction — the stressor is perceived, the SAM axis fires (adrenaline/noradrenaline within seconds), and there is an initial drop in physiological resistance as the body mobilises for emergency action. (2) Resistance/adaptation — the HPA axis sustains cortisol elevation over hours to days; resistance to the specific stressor rises above baseline while the body draws on metabolic reserves. Resistance to other stressors may actually fall during this stage. (3) Exhaustion — if the stressor persists and reserves are depleted, physiological defences fail: adrenal function declines, immune suppression becomes severe, and diseases of adaptation (peptic ulcers, cardiovascular disease, depression) emerge. GAS was ground-breaking in showing that chemically, physically, and psychologically diverse stressors all produce the same nonspecific pattern of adrenocortical activation.

Richard Lazarus and Susan Folkman's transactional model (1984) holds that stress is not a property of the stimulus or the organism in isolation, but of the transaction between them, mediated by cognitive appraisal. Primary appraisal evaluates: is this event irrelevant, benign-positive, or stressful (further categorised as harm/loss, threat, or challenge)? Secondary appraisal evaluates: what coping options are available? Stress occurs when perceived demands exceed perceived coping resources. The model explains why the same event (e.g. a job interview) produces intense stress in one person and excitement in another — individual appraisal patterns, not objective stressor severity, determine the response. Crucially, reappraisal (changing how the event is evaluated) is one of the most effective and studied emotion-regulation strategies, directly reducing physiological stress responses.

Allostatic load (McEwen & Stellar, 1993) is the cumulative physiological wear-and-tear on body systems resulting from repeated or chronic activation of stress-response mechanisms. Allostasis is the ability to maintain homeostasis through change — stress hormones, heart rate, and immune activity all adapt over time. But if these systems are chronically over- or under-activated, the adaptation itself becomes pathological. High allostatic load is operationalised as a composite of biological dysregulation markers: elevated cortisol, dehydroepiandrosterone, noradrenaline, adrenaline, blood pressure, waist-hip ratio, glycated haemoglobin, HDL cholesterol, and fibrinogen. High composite scores predict cardiovascular disease, cognitive decline, depression, and premature mortality — and accumulate unevenly along socioeconomic gradients, helping explain persistent health disparities.

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.

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.

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.