“Depression is very different between men and women,” said lead author Caroline Mnard, professor at the Faculty of Medicine at Universit Laval and researcher at the CERVO Brain Research Centre. “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 Mnard’s team showed that prolonged social stress in male mice weakened the blood-brain barrier separating 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 associated with reward and the control of emotions. The researchers found the same thing in the brains of men suffering from depression at the time of their death.
When Professor Mnard and her team repeated the experiment in female mice, they found that the brain barrier alterations caused by claudin-5 loss were located in the prefrontal 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 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 Mnard.” “In chronically stressed male mice and in men with depression, this part of the brain was unaltered. These findings suggest that chronic stress alters the brain barrier differently according to 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 through questionnaires,” said Mnard. “Our group is the first to show the importance of neurovascular health in depression and to suggest soluble E-selectin as a depression biomarker. It could potentially be used to screen for and diagnose depression. It could also be used to measure the efficacy of existing treatments or treatments in development. But first, large-cohort clinical studies will need to be conducted to confirm the biomarker’s reliability. These breakthroughs would not have been possible without the individuals and families who donate to the Douglas Bell Canada Brain Bank and the Signature Bank in Montral.”
In addition to Caroline Mnard, the coauthors of the article published in Nature Communications are Laurence Dion-Albert, Alice Cadoret, Ellen Doney, Fernanda Neutzling Kaufmann, Katarzyna A. Dudek, Batrice Daigle, and Manon Lebel (Universit Laval and CERVO Brain Research Centre); 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 et Naguib Mechawar (McGill University); Signature Consortium at Institut universitaire en sant mentale de Montral.