According to a recent study led by the Icahn School of Medicine at Mount Sinai, a type of RNA that has traditionally been overlooked plays an important role in promoting resilience to depression, specifically in females. The research highlights differences in how males and females change their minds when reflecting on past mistakes.
The study, published on July 11 in Science Advances, uncovers brain-region-specific and sex-dependent effects of this biomarker. It shows how individuals make certain types of decisions and reveals differences in how each sex decides whether to change their minds after making mistakes.
“Our motivation for this work stemmed from a major gap in understanding why depression is more prevalent in females,” said Brian Sweis, MD, PhD, Assistant Professor at the Icahn School of Medicine. “We set out to investigate how the brain at risk for developing depression thinks about one’s prior choices.”
The study builds on previous research involving non-coding RNA’s role in depression pathology. A 2020 study found reduced expression levels of LINC00473 RNA in the prefrontal cortex of women diagnosed with major depressive disorder.
Orna Issler, PhD, co-author of the current study, noted: “We translated these findings into an animal laboratory model and demonstrated a causal role of prefrontal LINC00473…in promoting resilience to stress in female mice only.”
Researchers manipulated LINC00473 levels in mice’s prefrontal cortex and observed changes in decision-making behavior related to sunk costs and regret—traits associated with resilience to stress.
“This research helps us appreciate that sensitivity to regret may not always be a bad thing,” explained Dr. Sweis. He emphasized that while ruminating on the past can be unpleasant, it can also contribute positively by helping individuals learn from experiences.
The implications are significant as this study identifies potential targets for new drug development and therapies for depressive symptoms related to negative rumination specifically for females.
Eric J. Nestler, MD, PhD remarked: “Translational cross-species research that includes leveraging animal models is crucial for making unexpected discoveries…and improved outcomes for those struggling with mental illnesses.”
This work was supported by various institutions including the National Institute of Mental Health and the American Psychiatric Association.
