Women are diagnosed with depression at about twice the rate of men, and experience different depression-related symptoms, such as increased experiences of negative rumination. A new study from scholars at the Icahn School of Medicine at Mount Sinai in New York has discovered a sex-specific genetic difference between the male and female brains that could explain this variation in depression symptomology.
For their study, the authors built on prior research that found women with major depressive disorder have lower levels of LINC00473, a non-coding RNA in the prefrontal cortex. Using mice as an animal model, the research team found that altering the levels of LINC00473 had a noticeable effect on female mice’s behavior. After observing mice foraging for food in a test environment with subjective value and a limited time budget, the authors found that female mice with higher levels of LINC00473 demonstrated increased stress resilience and flexibility in their decision-making, including how they valued the passage of time and weighed their prior mistakes. This increased sensitivity to sunk costs and regret influenced the female mice’s likelihood to revise their past choices. The same pattern was not found in male mice.
According to the authors, this study reveals new insights into sex-specific connections between neurobiology and behavior. Based on their findings, they believe LINC00473 is a viable target for developing new drugs for women suffering from negative rumination.
The research team also included scholars from New York University and the City University of New York’s Hunter College.