High Levels of Stress Hormone Linked to Changes in the Brain

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DNA modifications in the stress response gene FKBP5 found in the blood of mice exposed to high levels of the stress hormone cortisol have been directly linked to changes found in brain tissues.

Scientists at John Hopkins University made the discovery in relation to the stress response gene FKBP5, which has been previously linked to depression, bipolar disorder and post-traumatic stress disorder.

The findings point to a future when mental illness can be detected in blood, leading to better detection and treatment of mental disorders, as well as more accurate ways of testing whether medications are working.


Researchers have previously suspected that DNA changes found in the blood of mice exposed to high levels of stress hormone were directly related to changes found in their brain tissues. However, this is the first study to prove this and show that “epigenetic changes” – external modifications to DNA that turn genes “on” or “off” and that are detectable in blood – mirror alterations in brain tissue linked to underlying psychiatric disease.


FKBP5 is the stress response gene that has been found in a number of psychiatric disorders including depression, bipolar disorder, and post traumatic disorder.

This study reports only in relation to epigenetic changes to this particular gene, yet researchers point to the discovery of blood and brain matches present in dozens of other important genes that regulate vital processes in the brain.

The research is an exciting development. The guessing game of psychiatric diagnosis may well be over with practitioners in future being able to detect mental disorder within the blood. Study lead Richard S. Lee, Ph.D, comments on the new findings:

Many human studies rely on the assumption that disease-relevant epigenetic changes that occur in the brain — which is largely inaccessible and difficult to test — also occur in the blood, which is easily accessibleThis research on mice suggests that the blood can legitimately tell us what is going on in the brain, which is something we were just assuming before, and could lead us to better detection and treatment of mental disorders and for a more empirical way to test whether medications are working.” 


The study analysed the blood and brain of mice who suffered from a rodent version of Cushting’s disease – also known as “hypercortisolism” due to the collection of symptoms that develop in response to very high levels of the stress hormone cortisol.

Mice were given different doses of stress hormones in their drinking water to assess epigenetic changes to FKBP5 over a period of four weeks. Weekly blood samples were taken to measure changes that occurred in response to the increased cortisol.

The brains were then analysed at the end of the four weeks to investigate changes occuring in the hippocampus – a small but important part of the brain vital to memory, information storage and organizational abilities – as a result of high cortisol exposure.


Measurements showed that the higher the level of stress hormone in the mice, the greater the epigenetic changes to the blood and brain tissue. The scientists note that the brain changes occurred in a different part of the gene than expected, and made finding the blood-brain connection very challenging.

The study also showed that the more stress hormone the mouse was exposed to, the more RNA (Ribonucleaci Acid – a single strand of DNA that has been copied and tells the body which genetic codes to activate) from the FKBP5 gene was expressed in the blood and brain, and the greater the association with depression.

Epigenetic changes

However, it was the underlying epigenetic changes that proved more important than levels of RNA. While RNA levels return to normal after stress hormone levels decrease or change, epigenetic changes persist, reflect overall stress hormone exposure, and predict how much RNA will be made when stress hormone levels increase.

Elevated levels of stress hormone exposure are considered a risk factor for mental illness in humans and other mammals.


John Hopkins Press release: DNA Modifications Measure Blood Signal Related Changes in the Brain

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