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Hypothalamic-pituitary-adrenal axis

What is the hypothalamic-pituitary-adrenal (HPA) axis? 

Stress is defined as a threat to the body’s ability to regulate internal processes following exposure to an adverse event. People adapt physiologically and behaviourally in response to stress in order to re-establish internal balance. The biological response to stress is mediated through the HPA axis and the sympathetic nervous system. This is achieved through the release of cortisol and adrenocorticotropin hormone (ACTH). Altered HPA axis activity can result in prolonged exposure to cortisol or ACTH which can be detrimental to physical and psychological health. HPA activity can be measured by basal cortisol and ACTH levels in an unstressed or resting state. HPA activity can also be measured after a stressful stimulus (chemical or psychological). There is evidence that the HPA axis may be dysfunctional in a number of mental disorders, including schizophrenia.

What is the evidence on HPA axis functioning?

Moderate to high quality evidence suggests a small to medium-sized increase in blood cortisol levels in people with first-episode psychosis. There was a small overall increase in morning (≤10am) cortisol levels, a lower cortisol awakening response (high quality evidence), and a lower cortisol psychological stress response (moderate to low quality evidence) in people with schizophrenia compared to controls. Moderate to low quality evidence suggests increased cortisol levels are related to increased symptom severity.

There was also a lower cortisol awakening response in people with first-episode psychosis compared to controls (high quality evidence), with no differences in salivary basal cortisol levels (moderate quality evidence). For people with subclinical psychotic symptoms, there was no difference in the cortisol awakening response compared to controls (high quality evidence), but increased salivary basal cortisol levels were found (moderate quality evidence).

October 2020

Last updated at: 3:12 am, 27th October 2020
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Fact Sheet Technical Commentary

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Title Colour Legend:
Green - Topic summary is available.
Orange - Topic summary is being compiled.
Red - Topic summary has no current systematic review available.