Sex Differences in Depression: Including Transgender and Intersex Populations in Mental Health Research

In 2016, recognizing that lack of research in female animals was hampering the success of treatments for mood disorders, the National Institutes of Health (NIH) changed its policy for basic research to include sex as a biological variable for basic research, a move that triggered an explosion of research into sex differences.

Hodes and co-author Dawson Kropp, a Ph.D. student in neuroscience, reviewed some notable findings since the NIH mandate in an article recently published in the journal Nature Mental Health.

The following are among them:

• Compared to men, women have twice the risk of developing depression and anxiety disorders, experience their first episode of depression earlier, and have more cumulative episodes over their lifespan.
• Men are potentially underdiagnosed with major depressive disorder (MDD) because of sex differences in symptoms and they are more likely to externalize their symptoms, demonstrate anger or violence, and experience comorbid drug- or alcohol-use disorder.
• Various cell types in the brain have baseline and stress-induced sex differences. For example, microglia, the immune cells of the central nervous system, express baseline differences in men and women across development and in adulthood, which may contribute to sex differences across psychiatric disorders.
• Men seem to have greater vulnerability to prenatal or early-life stress exposure, resulting in stress-associated changes in physiology and behavior during the juvenile period. Changes in female behavior may not manifest until after puberty.
• Some tests with mice show that chronic variable stress -; recurrent physical, psychological, and social stress that is unpredictable and unavoidable -; can produce behavioral responses in women after only six days. A minimum of 21 days is needed to produce the same behavioral responses for those tests in men.