Finding Molecular Links between Stress and Depression

Vasco Sousa, researcher in Per Svenningson’s Group at CMM, is the first author of a study with the title “P11 deficiency increases stress reactivity along with HPA axis and autonomic hyperresponsiveness”, published online on October 1st in Molecular Psychiatry.

Experiencing severe stress or trauma can lead to chronic stress and abnormal stress responses, which is in turn associated with an increased risk of developing depression and anxiety. The underlying molecular mechanism are largely unknown, but research performed in Per Svenningson’s Group is now shedding more light on the regulation of such stress responses.

The group has previously found that a protein called p11 plays an important role in the function of serotonin, a mood-regulating signaling molecule in the brain (a neurotransmitter).

Through the newly published study, the CMM researchers, together with their collaborators from the Center for Neurogenomics and Cognitive Research, VU University, Amsterdam, also show that p11 is involved in the release of three different stress hormones in mice. It affects the initial release of the stress hormone cortisol by modulating the activity of specific neurons in the brain area hypothalamus, while by signaling through the brainstem, p11 regulates the release of adrenaline and noradrenaline. Additionally, in support for the significant role of p11 in stress regulation, mice lacking p11 showed stronger reactions to stress, measured through higher heart rate and more signs of anxiety, as compared to normal mice.

Vasco Sousa, Per Svenningsson and their colleagues hope that the link between p11, stress response and depression or anxiety, can be verified in patients and taken further to development of more effective treatments for these disorders.

Link to the publication: https://www.nature.com/articles/s41380-020-00887-0

Link to the press release at the Karolinska Institutet website: https://news.ki.se/new-clues-about-the-link-between-stress-and-depression

Vasco Sousa, Per Svenningsson and Ioannis Mantas (left to right), first, last and second authors of the publication.

Photo: Ulf Sirborn, Karolinska Institutet