The two faces of depression

Benoit Labonté

Benoit Labonté

Major depression affects the expression of genes in the brains of women and men differently

Major depression presents itself quite differently in women and men, and this dimorphism would have genomic foundations, suggests a study that has just been published in Nature Medicine. According to the first author of this study, Benoit Labonté of the CERVO Brain Research Centre at Université Laval, these differences are such that the search for new antidepressants would benefit from targeting mechanisms specific to each sex.

It was already known that major depression manifested itself differently in men and women. For example, in women, this mental disorder is up to three times more frequent, and its symptoms are exacerbated. Moreover, the efficacy of the same antidepressant varies according to the sex of the patients. To identify the cellular mechanisms underlying these differences, the thirty researchers who participated in the study turned to the brain bank at the Douglas Hospital Research Centre in Montreal. “We measured the expression of genes in the brains of 13 men and 13 women who suffered from major depression at the time of their death,” Professor Labonté explains. “For comparison purposes, we did the same analysis with the brains of 22 people who were not suffering from depression when they died. We restricted our analysis to brain RNAs whose integrity is well preserved in the hours following death. ”

The comparison confirmed that depression induces significant changes in brain genes expression in both men and women. The surprise came from the extent of the differences observed between men and women suffering from depression. “Barely 5 to 10% of the genes we studied are affected in the same way in subjects of both sexes,” summarizes Professor Labonté. It is the same disease, but, depending on the sex, it alters different mechanisms in the brain. We reached similar conclusions by studying the expression of genes in the brain of mice used as models of major depression. ” In light of these results, Benoit Labonté concludes that “several paths lead to depression”. The affected metabolic pathways seem to differ by gender, but these disturbances lead to common symptoms. “The search for new treatments should take this into account. It would be better to target the development of antidepressants that target gender-specific mechanisms, explains Labonté. They may be more effective and cause fewer side effects than classical antidepressants. ”

Source of text: Jean Hamann, Le Fil de l’Université Laval

English translation: CAN-ACN

Original research article:

Labonté B, Engmann O, Purushothaman I, Menard C, Wang J, Tan C, Scarpa JR, Moy G, Loh YE, Cahill M, Lorsch ZS, Hamilton PJ, Calipari ES, Hodes GE, Issler O, Kronman H, Pfau M, Obradovic ALJ, Dong Y, Neve RL, Russo S, Kazarskis A, Tamminga C, Mechawar N, Turecki G, Zhang B, Shen L, Nestler EJ. Sex-specific transcriptional signatures in human depression. Nat Med. 2017 Aug 21. doi: 10.1038/nm.4386.