Why do women experience major depressive disorder (MDD) at nearly twice the rate of men in the post-puberty stage? During this critical stage, MDD manifests in a sex-specific way in its prevalence, symptomatology, and treatment responses when comparing males and females.
In a recent publication in Brain, Behaviour, and Immunity, Corina Nagy, an assistant professor in McGill’s Department of Psychiatry and principal investigator at the Douglas Research Centre, examined puberty as a sensitive window when sex-dependent gene expression may occur and contribute to the manifestation of MDD in adults. Her interest in this topic grew from her PhD research, in which she noticed an imbalance in the representation of subjects in the literature investigating MDD in relation to sex.
“We were always focusing our research on male subjects,” Nagy said in an interview with The Tribune. “It was believed that it was easier to study males, and that the results in males could be generalized to females. But the more I looked into it and the more research that came out, it appeared that these results were not generalizable at all.”
Nagy emphasized the pubertal period as possessing a diverse interplay of many factors, similar to the gestational period—the time between conception and birth.
“[Puberty] is probably our most dynamic moment, where we have this secondary development and where we become sexually mature […] this is a vulnerability period for all psychopathologies, but in this context depression,” Nagy emphasized.
To address this sex-dependent divergence in the manifestation of MDD, Nagy and her team conducted a comprehensive review, presenting empirical evidence which points to puberty as the period during which the sex-specific framework of MDD is formed.
“We tried to examine the literature and look at all of the different systems at the molecular level [to show] there is a different scaffold that seems to be emerging in individuals and in animals,” Nagy told The Tribune.
Through systematic review of the literature and a summary of different studies’ results, Nagy’s findings indicate a clear association between the pubertal period and the development of depression. She emphasized that hormones contribute to women having twice the rate of MDD compared to men.
“We find that there are a lot of possibilities for these particular systems to be influenced by the change in [sex] hormones that occur at puberty,” Nagy explained. “This provides evidence for the hypothesis that the sex specific hormones are leading to a framework upon which different factors can influence the outcome of depression.”
Overall, Nagy’s work highlights how hormone levels—driven by a divergence in gene expression between males and females during puberty—shape the brain, immune system, and stress pathways distinctly, which consequently results in a difference in vulnerability to developing MDD.
Her research also alludes to the importance of female representation in research subjects, as well as the importance of understanding certain pathologies as more sex-specific than others.
“We need to be studying males and females in a disaggregated way, [studying] their sex-specific physiologies separately to understand it better,” she explained. “I think just having an awareness that being female is a vulnerability to certain pathologies is needed.”
According to the World Health Organization, as many as 280 million people live with MDD worldwide. Therefore, it is critical to understand these underlying mechanisms contributing to the development of MDD. This pathology affects many of us—our friends, family, and surrounding community.
“I think a lot of people know somebody who has survived depression, and of course, I am not unique in that way,” Nagy said.Since depression impairs one’s daily functioning, social relationships, and work performance, it is in both society’s and the McGill community’s interests to uncover the truth behind the development of depression—and this research is a phenomenal start.
