OCT 05, 2020 5:46 AM PDT

Gaining Insight Into the Connection Between Depression and Stress

WRITTEN BY: Carmen Leitch

Depression is a common mental illness, and stress is known to be an environmental influence that can increase the risk of depression. While there is still a lot to learn about the biochemistry underlying these links, scientists have learned that chronic stress and depression can cause changes in several parts of the brain including the hippocampus and neocortex.

Image credit: Pixabay/Graehawk

Using a mouse model, researchers have now found a protein in the brain that is involved in both the release of stress hormones and the function of serotonin, a neurotransmitter that functions in the regulation of mood. The work has been reported in Molecular Psychiatry by researchers at the Karolinska Institute.

Trauma or severe stress can lead to chronic stress or some other abnormal response in some people, which can raise a person's risk of developing other disorders like anxiety and depression. However, the regulation of the stress response, and how it may lead to these other issues, is not well-understood.

Previous work by the Karolinska Institute scientists has indicated that the p11 protein is relevant to how serotonin functions. People that have committed suicide and depression patients have been found to have lower levels of the p11 protein. In a mouse model of p11 reduction, there are behaviors that are correlated with depression and anxiety, and some antidepressants raise the levels of p11 in mice.

In this new work, the researchers used a mouse model to show that p11 can modulate the activity of neurons in the hippocampus, which impacts the release of cortisol, a stress hormone.

p11 can also act on a totally different biochemical pathway that starts in the brainstem that influences the release of adrenaline and noradrenaline, two stress hormones. Mice that have low levels of p11 also have a stronger reaction to stress: their heart rate gets higher and they have more anxiety-related behavior than mice with normal levels of p11.

"We know that an abnormal stress response can precipitate or worsen a depression and cause anxiety disorder and cardiovascular disease," said the first author of the study, Vasco Sousa, a researcher at the Department of Clinical Neuroscience, Karolinska Institute. "Therefore, it is important to find out whether the link between p11 deficiency and stress response that we see in mice can also be seen in patients."

The scientists are hopeful that this work will aid in the development of better therapeutics for these conditions. Current treatments for depression are often ineffective.

"One promising approach involves administration of agents that enhance localized p11 expression, and several experiments are already being conducted in animal models of depression," said the study leader Per Svenningsson, professor at the Department of Clinical Neuroscience, Karolinska Institute. "Another interesting approach which needs further investigation involves developing drugs that block the initiation of the stress hormone response in the brain."

Sources: AAAS/Eurekalert! Via Karolinksa Institute, Molecular Psychiatry

 

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