Dr. Marianne L. Seney, Dr. Jill Glausier, and Dr. Etienne Sibille published a major review in the journal Biological Psychiatry. They highlight how sex-specific factors might influence not only susceptibility or resilience to depression, but also how these factors might result in divergent pathology in men and women.
Abstract:
Major depressive disorder (MDD) is a leading cause of disability, affecting more than 300 million people worldwide. We first review the well-known sex difference in incidence of MDD, with women being twice as likely to be diagnosed as men, and briefly summarize how the impact of MDD varies between men and women, with sex differences in symptomatology, severity, and antidepressant drug response. We then attempt to deconstruct the biological bases for MDD and discuss implications for sex differences research. Next, we review findings from human postmortem studies, both from selected candidate gene studies as well as from well-powered, unbiased transcriptomic studies, which suggest distinct, and possibly opposite, molecular changes in the brains of depressed men and women. We then discuss inherent challenges of research on the human postmortem brain and suggest paths forward which rely on thoughtful cohort design. Although studies indicate that circulating gonadal hormones might underlie the observed sex differences in MDD, we discuss how additional sex-specific factors, such as genetic sex and developmental exposure to gonadal hormones, may also contribute to altered vulnerability, and highlight various nuances we believe should be considered when determining mechanisms underlying observed sex differences. Together, this review highlights how various sex-specific factors might influence not only susceptibility or resilience to depression, but also how those sex-specific factors might result in divergent pathology in men and women.
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