A new study from Virginia Tech College of Science’s School of Neuroscience urges more research into sex differences in depression.
In 2016, recognizing that lack of research in female animals was hampering the success of treatments for mood disorders, the U.S. National Institutes of Health changed its policy for basic research to include sex as a biological variable for basic research. This policy triggered an increase of research into sex differences.
In a call for a new wave of research activities into differences in biological sex, Georgia Hodes, assistant professor in the School states: “Building a strong unbiased foundation of literature will help uncover more effective and sex-specific biomarkers for depression onset and target better treatment.”
This is because 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.
In addition, 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.
Furthermore, men seem to have greater vulnerability to prenatal or early-life stress exposure, resulting in stress-associated changes in physiology and behaviour during the juvenile period. Changes in female behaviour may not manifest until after puberty.
There are some underlying biological reasons at play. For instance, 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.
The reason for the focus on animal models based on sex differences is borne out in some tests with mice show that chronic variable stress — recurrent physical, psychological, and social stress that is unpredictable and unavoidable — can produce behavioural responses in women after only six days. A minimum of 21 days is needed to produce the same behavioural responses for those tests in men.
These key arguments are set out in the journal Nature Mental Health (“Sex as a biological variable in stress and mood disorder research”). In addition to discussing the research, the article addresses the need for pharmaceutical companies to recognise that depression is a heterogeneous disorder and that one pill will not fit all.
The researchers propose that future studies need to go beyond whether there are sex differences and start asking why there are sex differences and how these differences can help with developing personalized therapeutics.
