Abstract
Mood disorders are devastating, often chronic illnesses characterized by low mood, poor affect, and anhedonia. Notably, mood disorders are approximately twice as prevalent in women compared to men. If sex differences in mood are due to underlying biological sex differences, a better understanding of the biology is warranted to develop better treatment or even prevention of these debilitating disorders. In this review, our goals are to: 1) summarize the literature related to mood disorders with respect to sex differences in prevalence, 2) introduce the corticolimbic brain network of mood regulation, 3) discuss strategies and challenges of modeling mood disorders in mice, 4) discuss mechanisms underlying sex differences and how these can be tested in mice, and 5) discuss how our group and others have used a translational approach to investigate mechanisms underlying sex differences in mood disorders in humans and mice.
Highlights
Mood disorders are devastating, often chronic illnesses characterized by low mood, poor affect, and anhedonia
Major depressive disorder (MDD) is defined as a syndrome that includes prominent emotion dysregulation, low mood, poor affect, and/or anhedonia; these core MDD symptoms are accompanied by cognitive symptoms, physiological symptoms [9], and frequent co-morbid high anxiety symptoms [9,10]
Even though the SST, glutamate decarboxylase 1 (GAD1), and glutamate decarboxylase 2 (GAD2) genes are not located on the X chromosome, we found several X chromosome single nucleotide polymorphism (SNP) associated with expression of these three genes; these results suggest the possibility of transregulation of SST, GAD1, and GAD2 by X chromosomeencoded factors [89]
Summary
There is clear evidence that women are more vulnerable to develop mood disorders compared to men This sex difference seems to have a biological basis, as we have found sex differences in expression of mood-related genes in the brains of depressed subjects. Our mouse studies show that while testosterone has a potent effect of decreasing anxiety-like behavior, it does not seem to be doing so via effects on GABA-, serotonin-, or dopamine-related gene expression [89,116]. We believe that preliminary studies using appropriate mouse models, with consideration of trait and state, as well as the multiple dimensions of mood-related behaviors, can provide a framework to systematically dissect the biological underpinnings of sex differences in mood in humans. Authors’ contributions Both authors read and approved the final manuscript
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