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What is the HPA (Hypothalamic-Pituitary-Adrenal) axis?

When you encounter a stressor: hypothalamus → pituitary → adrenal glands → cortisol

Cortisol prepares the body for

action — raises blood sugar, suppresses immune activity, sharpens attention.

The hippocampal brake

the hippocampus has lots of cortisol receptors. When cortisol gets high enough, it tells the hippocampus to signal the hypothalamus to stop producing more cortisol — a negative feedback loop (like a thermostat turning off the heating).

Chronic stress breaks the hippocampus brake

Sustained cortisol damages hippocampal neurons, reducing its ability to shut off the HPA axis — leading to chronically elevated cortisol and lasting brain changes

Allostasis

stability through change - the body doesn't have a fixed set-point; it anticipates demands and adjusts. Cortisol even rises before a stressful event you're expecting.

Allostatic load

the cumulative "wear and tear" from repeated stress when the body never fully recovers. Think of it as a stress debt that builds up over time and predicts poor long-term health outcomes

The Dunedin Study found that childhood adversity predicts accelerated biological aging at age

45. Early stress leaves a measurable biological mark.

Pups raised by high-LG (licking and grooming) mothers grow up

less anxious and less stress-reactive

When pups of low-LG mothers are cross-fostered to high-LG mothers, they grow up

resilient — showing the effect is environmental, not just genetic.

what is the mechanism behind high LG and low LG mothers

high-LG mothering changes DNA methylation on the glucocorticoid receptor gene in the pup's hippocampus. More receptors = better HPA feedback brake = lower stress reactivity. This is epigenetics — the environment changing gene expression without changing the DNA sequence itself.

children assigned to high quality foster care showed

substantial recovery — but only if moved before ~24 months of age. After that, effects became progressively harder to reverse.

the orphanage study demonstrated

sensitive periods - windows in early development when the brain is most responsive to experience — for good or bad.

Classic story (Seligman & Maier, 1967): dogs given inescapable shocks later

didn't try to escape even when they could — as if they had "learned" to be helpless.

Update to the Classic Story in 2016

the original story was backwards. Passivity is the brain's default response to inescapable stress — not something learned. What is learned (with control) is how to override that default passivity.

mechanism behind inescapable stress

inescapable stress activates dorsal raphe serotonin neurons → passivity. Escapable stress recruits the PFC → PFC inhibits the raphe → agency is restored. Same shock, different brain response, depending on perceived control.