Severe Depression Affects Women and Men Differently – Scientists May Have Finally Discovered Why

A team of Université Laval scientists may have discovered why severe depression affects women and men differently, according to a study published on January 10, 2022, in Communicating Nature. The researchers examined the brains of people with depression at the time of death and found changes located in different parts of the brain for each sex. They also identified a potential biomarker of depression in women.

“Depression is very different between men and women,” said lead author Caroline Ménard, a professor in the Faculty of Medicine at Université Laval and a researcher at the CERVO Brain Research Center. “In women, the disease is twice as common, the symptoms are different, and the response to antidepressants is not the same as in men. Our goal was to find out why. ”

In a previous study, Caroline Ménard’s team showed that prolonged social stress in male mice weakens the blood-brain barrier that separates the brain from peripheral blood circulation. These changes were due to the loss of a protein called claudin-5 and were evident in the nucleus accumbens, a part of the brain involved in reward and emotion regulation. The researchers found the same thing in the brains of men suffering from depression at the time of their death.

When Professor Ménard and her team repeated the experiment in female mice, they found that the changes to the brain barrier caused by claudin-5 loss were located in the precursor cortex. Their findings were the same when they examined the brains of women suffering from depression at the time of their death. In men, however, the precursor cortex blood-brain barrier was not affected.

“The precursor cortex is about mood regulation, but also anxiety and self-perception,” explains Professor Ménard. ” “In chronically stressed male rats and in depressed men, this part of the brain was unchanged. These findings suggest that chronic stress changes brain barrier differently by gender. ”

As they investigated further, the researchers discovered a blood marker related to brain barrier health. The marker, soluble E-selectin, is an inflammatory molecule found at higher concentrations in the blood of stressed female mice. It is also present in blood samples of women with depression, but not in men.

“Today, depression is still being diagnosed through questionnaires,” said Ménard. “Our group is the first to demonstrate the importance of neurovascular health in depression and to suggest soluble E-selectin as a biomarker of depression. It can be used to screen for and diagnose depression. It could also be used to measure the effectiveness of existing treatments or treatments in development. But first, large cohort clinical studies will need to be conducted to confirm the biomarker reliability. These developments would not have been possible without the individuals and families who donate to Douglas Bell’s Canadian Brain Bank and the Signature Bank in Montréal. ”

Reference: “Vascular and blood-brain changes associated with obstruction underlie stress responses and resilience in female mice and depression in human tissue” by Laurence Dion-Albert, Alice Cadoret, Ellen Doney, Fernanda Neutzling Kaufmann, Katarzyna A. Dudek , Beatrice Daigle, Lyonna F. Parise, Flurin Cathomas, Nalia Samba, Natalie Hudson, Manon Lebel, Signature Consortium, Matthew Campbell, Gustavo Turecki, Naguib Mechawar and Caroline Menard, 10 January 2022, Communicating Nature.
DOI: 10.1038 / s41467-021-27604-x

In addition to Caroline Ménard, the co-authors of the article published in Communicating Nature are Laurence Dion-Albert, Alice Cadoret, Ellen Doney, Fernanda Neutzling Kaufmann, Katarzyna A. Dudek, Béatrice Daigle, and Manon Lebel (Université Laval and CERVO Brain Research Center); Lyonna F. Parise and Flurin Cathomas (Icahn School of Medicine at Mount Sinai); Nalia Samba (Sorbonne); Natalie Hudson and Matthew Campbell (Trinity College Dublin); Gustavo Turecki and Naguib Mechawar (McGill University); Signature Consortium at Montreal University University of Mental Health.

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