New Clues about the Link Between Stress and Depression

Sep 14, 2023 | Depression, Stress

Scientists from Karolinska Institutet in Sweden have made a significant discovery related to a brain protein that plays a crucial role in both regulating the mood-regulating substance serotonin and the release of stress hormones, at least in mice. Their findings, published in the journal Molecular Psychiatry, could potentially lead to the development of novel drugs for treating depression and anxiety.

When individuals experience trauma or severe stress, some may develop abnormal stress responses or chronic stress, which increases the risk of developing other conditions like depression and anxiety. However, the mechanisms behind this and how stress responses are regulated remain unknown.

The Study

The research team at Karolinska Institutet previously demonstrated that a protein called p11 is vital for serotonin function, a neurotransmitter that regulates mood in the brain. Patients with depression and suicide victims tend to have lower levels of p11 in their brains, and laboratory mice with reduced p11 levels exhibit behavior resembling depression and anxiety. Additionally, certain antidepressants can raise p11 levels in mice.

In the new study, researchers found that p11 affects the initial release of the stress hormone cortisol in mice by influencing specific neurons in the hypothalamus, an area of the brain. Through a different signaling pathway originating in the brainstem, p11 also impacts the release of two other stress hormones, adrenaline and noradrenaline. Moreover, tests showed that mice lacking p11 react more strongly to stress, exhibiting higher heart rates and more signs of anxiety compared to mice with normal p11 levels.

The lead author of the study, Vasco Sousa, a researcher at the Department of Clinical Neuroscience, Karolinska Institutet, emphasizes the importance of investigating whether the link between p11 deficiency and stress response observed in mice can also be seen in patients. Understanding this connection may help improve treatment approaches for conditions related to abnormal stress responses.

The Findings

The researchers suggest that these findings could lead to the development of more effective drugs. Current antidepressants are not sufficiently effective for many patients, making the search for new treatments critical. One promising approach involves using agents that enhance localized p11 expression, and experiments are already underway in animal models of depression. Another interesting avenue for exploration is the development of drugs that block the initiation of the stress hormone response in the brain.

In summary, this research provides valuable insights into the role of the p11 protein in regulating serotonin function and stress hormone release in mice. The findings offer potential opportunities for the development of new drugs to address depression and anxiety, addressing the limitations of current antidepressant treatments. Further research is needed to explore these avenues and determine if the findings can be translated to human patients.

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