Sex as a biological variable in stress and mood disorder research

In 2016, changes were mandated for basic research, including using sex as a biological variable. This policy change was due to the lack of research performed in female animals. This resulted in a mismatch between the sex of the subjects being used for drug development and the sex of the participants in subsequent clinical trials hampering the translational success of novel therapeutics, especially treatments for mood disorders. While it is now clear that sex differences exist, the field needs to move to the next frontier in sex-difference research. We need to start exploring why and how these sex differences exist. What are their functions? How do we harness this information to develop novel sex-specific treatments for mental illness? This Review will address what we have learned from using sex as a biological variable and how we can utilize these data to better understand and treat sex-based disparities in mental health. In this Review, Hodes and Kropp discuss the lessons we have learned from using sex as a biological variable in stress and mood disorder research and how we should shape our questions to avoid sex-based disparities in mental health care.