The HPA Axis & Stress

The alarm reaction: the body's immediate response to a stressor — involving SAM-axis activation (adrenaline, noradrenaline) and initial HPA triggering; physical resistance to the stressor may temporarily decrease. The resistance stage: sustained mobilisation; the HPA axis dominates — cortisol is chronically elevated to maintain energy, suppress inflammation, and allocate resources to the threat. The body appears to cope, but at physiological cost. The exhaustion stage: if the stressor persists too long or too intensely, adaptive resources are depleted — cortisol output falls, immune function collapses, and the organism becomes vulnerable to disease. Selye originally proposed this as a universal response to any prolonged demand, regardless of its nature.

Lazarus and Folkman (1984) proposed that stress is not in the event itself but in the person's appraisal of it. Primary appraisal evaluates whether the situation is relevant and, if so, whether it is a threat, challenge, or harm/loss. Secondary appraisal assesses available coping resources — what can be done. Stress is experienced when demands are appraised as exceeding coping capacity. This model explains individual variation: the same exam is catastrophic for one student and an exciting challenge for another. It also underpins cognitive-behavioural therapy for stress, which targets maladaptive appraisals through cognitive restructuring.

Allostasis is the process of adapting to demands by varying physiological parameters (blood pressure, cortisol, glucose) around a set point. Allostatic load (McEwen & Stellar, 1993) is the cumulative cost — "wear and tear" — of repeated or chronic allostatic activation. It manifests as elevated resting cortisol, suppressed immune function, visceral adiposity, dysregulated blood pressure, hippocampal atrophy, and increased vulnerability to cardiovascular disease and type 2 diabetes. Allostatic overload occurs when demands consistently exceed the organism's capacity to adapt — the mechanism behind the well-established link between chronic psychosocial stress and poor physical and mental health outcomes.

Chronically elevated cortisol acts on glucocorticoid receptors (GR) throughout the brain. Its most damaging effect is on the hippocampus, which has the highest density of GRs in the brain. Sustained cortisol causes dendritic retraction, reduced neurogenesis, and eventually neuronal death in the CA3 subfield — producing measurable volume reduction. This impairs episodic memory and — critically — damages the hippocampus's role in providing inhibitory feedback to the HPA axis (via GR-mediated suppression of CRH), further dysregulating the stress response. The amygdala, by contrast, becomes hyperactivated by chronic stress, enhancing fear responses. The net effect is a fearful, memory-impaired individual with a stress system that no longer turns off properly.