Research published today in Nature Communications by Université Laval scientists may have thrown light on why severe depression affects women and men in different ways.
The researchers analyzed the brains of persons who died from depression and observed changes in various areas of the brain for each sex.
They also discovered a possible biomarker for depression in women.
Université Laval professor and CERVO Brain Research Center researcher Caroline Ménard says “depression is very different between men and women. 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.”
Caroline Ménard’s team previously demonstrated that chronic social stress weakens the blood-brain barrier, which separates the brain from peripheral blood circulation, in male mice. These changes were seen in the nucleus accumbens, a portion of the brain related to reward and emotion control, and were caused by the loss of a protein called claudin-5. A similar thing was discovered in the brains of males who were depressed at the time of their deaths.
After conducting the experiment on female mice, Professor Ménard and her team discovered that changes in the prefrontal cortex were caused by the loss of claudin-5. When they looked at the brains of women who had died from depression, they discovered the same thing. The prefrontal cortex’s blood-brain barrier, on the other hand, was unaffected in men.
“The prefrontal cortex is involved in mood regulation, but also in anxiety and self-perception,” explains Professor Ménard. “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 dug deeper, the researchers uncovered a blood signature connected to brain barrier health. Soluble E-selectin, the marker, is an inflammatory molecule that was detected in increased concentrations in the blood of stressed female mice. It is also present in the blood of women suffering from depression, but not in men.
The author adds: “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 Montréal.”
Source: 10.1038/s41467-021-27604-x
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