Women More Prone to Regret? New Study Uncovers Brain Decision-Making Mechanisms

Do women regret more easily? A new study uncovers the brain’s decision-making mechanisms

Repeatedly weighing sunk costs and fixating on past wrong choices are core features of "rumination"—and a source of suffering, especially for female patients with depression.

Regret is common, but being trapped in dwelling on past mistakes may be a typical symptom of depression: "negative rumination" over adverse experiences. The global incidence of depression is twice as high in women as in men, and the biological mechanisms behind these gender-specific thought patterns have long been a puzzle for the scientific community.

Recently, a study indicates that subjective evaluation after decision-making is regulated by complex molecular mechanisms in the brain, with significant gender differences. Researchers identified a depression-related molecule that precisely regulates the "changing one’s mind" phase in decision-making, particularly prominently in female mice. The study was published in Science Advances on July 11, 2025, by a team from the Icahn School of Medicine at Mount Sinai, USA.

Molecular switch for decision-making, stress, and depression

The study focuses on LINC00473, a long non-coding RNA. "Non-coding" means it does not directly produce Proteins but acts as a "regulator" in gene expression. Previous studies found that LINC00473 expression is significantly lower in the medial prefrontal cortex (mPFC) of female depression patients, but not in male patients. Artificially increasing this molecule’s expression in female mice’s brains effectively enhances their stress resistance.

How does this "molecular switch," closely linked to female depression and stress, affect brain function? The research team hypothesized the answer lies in its regulation of cognitive and decision-making behaviors. They focused on the medial prefrontal cortex—a key brain region responsible for weighing pros and cons, self-control, and emotional regulation, and where LINC00473 mainly functions.

"Restaurant Row" experiment: "Sunk costs" and "regret"

To observe decision-making processes precisely, the team built an experimental setup called "Restaurant Row." In this maze-like device, mice needed to navigate and forage from four "restaurants" offering different food flavors within 30 minutes. Each foraging trip tested their decision-making ability, broken into two linked phases.

First, mice entered an "offer zone," where they heard a tone—higher pitch meant longer waiting time for food, i.e., "cost." Here, they had to make an initial, deliberate judgment: accept the offer or skip it for a better opportunity.

If they accepted, they then entered a "waiting zone," facing a more challenging inner struggle: persist until the end or give up midway? "Giving up" at this point is a typical "changing one’s mind," reflecting one’s ability to re-evaluate the situation after investing time and energy.

Gender-specific regulation of LINC00473

Results clearly showed LINC00473’s effects are highly selective. It had no impact on mice’s initial judgments in the "offer zone"—all mice, regardless of gender, showed unchanged strategies in accepting or rejecting offers. However, once in the waiting zone where "changing one’s mind" was needed, LINC00473 exerted its powerful gender-dependent regulation.

Researchers focused on two indicators reflecting advanced cognitive processes. The first was "sunk cost sensitivity"—how already invested time costs affect the willingness to continue waiting. They found LINC00473 significantly enhanced female mice’s sunk cost sensitivity, meaning after waiting a while, they valued the time already spent more and were more likely to persist.

The second indicator was "regret sensitivity." After making a mistake (e.g., entering a high-cost waiting zone then giving up), would mice learn lessons and adjust their next decision? Results showed LINC00473 effectively improved female mice’s regret sensitivity, making them more flexible in adjusting future strategies after errors.

Linking decision-making and emotion

Why does LINC00473 affect both sunk cost and regret behaviors? Researchers suggest they may stem from a common psychological process called "counterfactual thinking"—imagining "what if I had chosen differently." When a mouse mistakenly enters a high-cost waiting zone and gives up, its brain may simulate "I should have skipped it"—a process regulated by LINC00473.

This discovery goes beyond decision-making. Fixating on sunk costs and past wrong choices are core features of "rumination"—and sources of suffering for depression patients, especially women. The study establishes a clear pathway: a molecule (LINC00473) with lower levels in female depression patients directly regulates cognitive processes similar to negative thinking, with significant gender differences. It not only provides new biological evidence for why women are more vulnerable to depression but also points to directions for developing new interventions targeting specific cognitive processes.