Stress and the Brain

The stress response from Selye to the HPA axis, why short-term stress helps and chronic stress harms, effects on memory and the hippocampus, and evidence-based ways to manage stress.

From Selye to the HPA axis

In the 1930s the Hungarian-Canadian endocrinologist Hans Selye noticed that rats exposed to many different unpleasant situations — cold, injury, toxins — developed the same pattern: enlarged adrenal glands, shrunken immune organs and stomach ulcers. He called this the general adaptation syndrome and popularised the word "stress".

We now know the stress response has two main arms. The fast arm is the sympathetic nervous system and adrenaline, working within seconds: heart rate up, energy mobilised. The slower arm is the HPA axis: the hypothalamus releases CRH, the pituitary releases ACTH, and the adrenal glands release cortisol over minutes. Cortisol raises blood sugar, damps inflammation, and acts on the brain — including the hippocampus and prefrontal cortex, which help switch the response off through negative feedback.

Good stress, bad stress

Short-term stress can be useful: it sharpens attention and strengthens memory for important events. Performance often rises with moderate arousal and falls with too much. The problem is chronic stress — and the neuroendocrinologist Bruce McEwen described its cumulative wear and tear as allostatic load.

Stress on the brain

In animal studies, prolonged high glucocorticoid levels cause dendrites in the hippocampus and prefrontal cortex to shrink, while dendrites in the amygdala grow — a shift toward vigilance and away from flexible thinking. Some of these changes reverse when stress ends. In humans, chronic stress is associated with poorer memory and concentration, sleep problems, and higher risk of depression, anxiety, cardiovascular disease and other illnesses. Early-life adversity can have long-lasting effects on stress systems.

What helps

Evidence supports regular physical activity, adequate sleep, social connection, and approaches such as cognitive behavioural therapy and mindfulness-based programmes for many people. Controllability matters: in classic studies, animals that could control a stressor fared far better than those that received the identical stressor with no control, and a sense of agency is protective in people too.