The biological response to stress is mediated through the Hypothalamic-Pituitary-Adrenal (HPA) axis and the sympathetic nervous system. Cortisol and the steroid hormone dehydroepiandrosterone (DHEA) and its sulfate form DHEA-S are important for elucidating the role of HPA dysfunctions in PTSD. Stress is 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 to re-establish internal balance. Altered HPA axis activity can be detrimental to physical and psychological health.

What is the evidence for HPA dysfunction in people with PTSD?

Moderate to high quality evidence found small decreases in morning and 24-hour cortisol levels in people with PTSD compared to controls. The effect was larger in studies with non-trauma-exposed controls than in studies with trauma-exposed controls. Moderate quality evidence found no significant changes in cortisol levels or in the cortisol awakening response following psychosocial treatments for PTSD.

Moderate to high quality evidence found no significant differences in DHEA or DHEA-S levels compared to controls, apart from higher evening DHEA levels in people with PTSD when compared to non-trauma exposed controls.

August 2021

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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.

What is the evidence for HPA axis anomalies?

High quality evidence suggests a small to medium-sized increase in awakening and post-dexamethasone cortisol levels in people with bipolar disorders compared to controls. Moderate to high quality evidence suggests morning, nighttime and 12-24hour cortisol levels may also be increased. The manic phase of the illness was associated with the largest effect sizes, while the use of antipsychotics was associated smaller effect sizes. Radioimmunoassay method of measurement and older age were associated with trend effects for larger effect sizes.

Moderate quality evidence suggests ACTH, but not corticotropin-releasing hormone, is also increased in people with bipolar disorder.

There were no differences in morning cortisol levels between people with bipolar disorder or schizophrenia.

December 2021

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