About this Research Topic

Background

Anxiety and depression are major global psychiatric health burdens, affecting hundreds of millions of individuals worldwide. Both are characterized clinically by significant sex differences, with women being twice as likely to be diagnosed with an anxiety disorder or major depressive disorder in their lifetimes. These differences have been attributed to biological, as well as cultural and social factors. Furthermore, men and women differ in symptomatology and responses to psychotropic agents, highlighting the need for a better understanding of the mechanisms leading to these sex differences.

Animal models have been employed over many years to study anxiety and depression. However, male animals have been traditionally used in pre-clinical studies, perhaps due to less complicated experimental designs. The inclusion of both sexes in preclinical research presents an opportunity to explore sex differences in the biological underpinnings (e.g., inflammation, neurotransmitter dysregulation), contributions of stress (e.g., maternal separation, chronic mild stress), and other influences (e.g., resiliency, genetics and epigenetics, social factors, gut microbiota) that may underlie emotional dysregulation and abnormal performance at behavioral endpoints (e.g., forced swim test, sucrose preference test, elevated plus maze). Unfortunately, animal models have yielded inconsistent results and often report greater anxiety- or depressive-like symptoms in male animals than in female animals. For example, a recent study found that the frequently-employed chronic unpredictable mild stress model was more likely to induce depressive-like behaviors in male, than in female, rats. These inconsistencies call for better standardization and normalization when designing experiments exploring sex differences underpinnings.

The aim of this Research Topic is to explore the utility of animal models in the study of sex differences in neuropsychiatric disease. We welcome original research or reviews that address outstanding questions in the pre-clinical literature regarding this topic, including but not limited to:

• How can we improve behavioral outcomes in animal models to better represent sex differences in clinical symptoms?
• How are behavioral tests best standardized when working with males and females?
• How does stress differentially contribute to anxiety- and depressive-like symptoms in animal models?
• How does hypothalamic-pituitary-adrenal (HPA) axis function differ in male and female animals, contributing to neuropsychiatric dysfunction?
• How does the genetic and molecular pathophysiology of anxiety and/or depression differ between male and female animals?
• What are the mechanisms underlying differences between males and females in responses to anti-anxiety and anti-depressive agents?
• Can we ever fully model the human experience of depression in rodent models when some symptoms (e.g., sadness, suicidality, introspection) cannot be adequately measured, and when some contributing factors (e.g., social, cultural) are not present in the same way as in the human condition?

Keywords: Sex Differences, Stress, Depression, Anxiety, Sex Hormones

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