A team of scientists at Université Laval may have discovered why severe depression affects women and men differently, according to a study published in Nature Communications.
Researchers examined the brains of people with depression at the time of death and discovered alterations located in different parts of the brain for each sex. They also identified a possible biomarker of depression in women.
"Depression is very different between men and women," said lead author Caroline Ménard, a professor at Université Laval Faculty of Medicine and 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 weakened the blood-brain barrier that separates the brain from the 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 associated with reward and emotion control. The researchers found the same thing in the brains of men who were 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 brain barrier alterations caused by the loss of claudin-5 were located in the prefrontal cortex . Their findings were the same when they examined the brains of women who were suffering from depression at the time of their death. In men, however, the blood-brain barrier of the prefrontal cortex was not affected .
“The prefrontal cortex is involved in mood regulation, but also in anxiety and self-perception,” explained Professor Ménard. “In male mice with chronic stress and in men with depression, this part of the brain was not altered. "These findings suggest that chronic stress alters the brain barrier differently depending on gender."
As they investigated further, the researchers discovered a blood marker linked 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 diagnosed by questionnaires,” Ménard said. “Our group is the first to show the importance of neurovascular health in depression and to suggest soluble E-selectin as a biomarker of depression. Potentially, it could be used to detect 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 reliability of the biomarker. “These advancements would not have been possible without the individuals and families who donate to Douglas Bell Canada Brain Bank and Signature Bank in Montreal.”
In addition to Caroline Ménard, the co-authors of the article published in Nature Communications 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 Institut universitaire en santé mentale de Montréal.
