Understanding depression and anxiety
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# 2.1 The operation and control of the HPA axis

The following activity includes an interactive animation that will help you to appreciate the nature of stress and the role played by stress and the hypothalamic–pituitary–adrenal (HPA) axis when we come to consider the aetiology of emotional disorders such as depression and anxiety.

The animation is designed to help you understand the operation of the HPA axis – how it is controlled under normal conditions and how the controls are disrupted under conditions of chronic stress.

## Activity 6 The operation and control of the hypothalamic–pituitary–adrenal (HPA) axis

Allow 1 hour

The stress response has evolved to mobilise the body and mind for action when a threat is perceived. The response has two main strands which act in parallel. The first is the sympathetic response, which triggers the release of adrenalin from the medulla of the adrenal gland. The second strand involves the hypothalamic–pituitary–adrenal, or HPA, axis, and triggers the release of cortisol from the cortex of the adrenal gland.

In this activity you will look at the operation and control of the HPA axis in three different conditions – first, under normal relaxed or baseline conditions; second, under normal conditions when there is an episode of stress which is resolved; and third, under conditions of continual or chronic stress when regulation of the HPA axis breaks down.

#### Overview of the HPA axis flow diagram

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Transcript

#### Baseline, acute and chronic stages

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#### Re-run of HPA animation stages

Baseline

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Acute

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Chronic

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#### HPA axis components: more information

Identify two factors from the list below that would help to bring cortisol levels back to baseline levels after experiencing a stressful event.

(a) The positive feedback loop.
(b) Stimulation by the amygdala.
(c) Enzymes in the blood that break down cortisol.
(d) The negative feedback loop.
(e) The secretion of ACTH.

Identify the correct statements about cortisol from the following:

(a) Cortisol is released upon stimulation of the adrenal cortex by ACTH.
(b) Cortisol is released upon stimulation of the adrenal cortex by CRF.
(c) Cortisol attaches to glucocorticoid receptors on the adrenal cortex.
(d) Cortisol has an inhibitory effect on secretion of ACTH by the pituitary.
(e) Cortisol attaches to glucocorticoid receptors.

Go through the sequences showing the acute and chronic stress conditions again.

Go through the sequences showing the acute and chronic stress conditions again.

Cortisol acts via glucocorticoid receptors to inhibit the activity of the HPA axis, so less cortisol is secreted. Why does cortisol become less effective in inhibiting the HPA axis during chronic stress? Select the best explanation from the list below.

(a) Because the high levels of cortisol present during chronic stress damage the glucocorticoid receptors via which cortisol exerts an inhibitory effect on the HPA axis.
(b) Because there is less cortisol present during chronic stress to exert an inhibitory effect on the HPA axis, including on the hypothalamus and the pituitary.
(c) Because there is more activity in the HPA axis during chronic stress, as the axis is constantly being stimulated by stressors to release CRF, ACTH and cortisol.

## Answer

Statement (a) provides the best explanation for why cortisol becomes less effective in inhibiting the HPA axis during chronic stress. Statement (b) is incorrect because there is more, not less, cortisol present during chronic stress. Statement (c) is correct in that there is more activity in the HPA axis during chronic stress, but it does not explain why cortisol fails to control the activity of the HPA axis.

Select, from the following, the statement(s) that explain why the high activity of the HPA axis during chronic stress can affect how we feel and act.

(a) The adrenalin secreted makes us more alert and makes our hearts beat faster.
(b) High levels of cortisol secreted during chronic stress can damage neurons in the hippocampus, which can affect conscious memories, including recall of events and facts.
(c) High levels of cortisol secreted during chronic stress can damage neurons in the prefrontal cortex, which can affect our ability to evaluate and plan, and to make judgements.
(d) The amygdala is less active when the HPA axis is more active, so we are less likely to react to stressors.
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