Why Depression Hits Women Harder Than Men? Study Sheds Light

A study published in Nature Communications has identified over 6,000 gene variants that may explain why depression affects women more than men. The research found that, in addition to the 7,000 variants shared with men, women had 6,133 unique genetic markers linked to major depressive disorder (MDD), providing new insights into the biological basis of this mental health condition.

Depression is one of the most common mental illnesses worldwide, and women are twice as likely to be diagnosed with it compared to men. Until now, the reasons behind this disparity remained unclear.

To identify the reasons, the team screened genetic data from around 130,000 women and 65,000 men with depression across Australia, the Netherlands, the UK, and the US. For comparison, genetic data from nearly 160,000 women and over 130,000 men without depression were also included.

The analysis revealed that all 7,111 causal variants for major depressive disorder in males were shared with major depressive disorder in females, with an additional 6,133 variants unique to major depressive disorder in females and zero variants unique to major depressive disorder in males. This suggests that genetic factors play a larger role in depression risk among women than men.

Interestingly, the genetic variants in women were more strongly associated with metabolic traits. Researcher Jodi Thomas explained that this "may help explain why females with depression more often experience metabolic symptoms, such as weight changes or altered energy levels.”

The findings reinforce the importance of considering sex-specific genetic influences in studying depression and other complex health conditions.

Reference: Thomas, J.T., Thorp, J.G., Huider, F. et al. Sex-stratified genome-wide association meta-analysis of major depressive disorder. Nat Commun 16, 7960 (2025). https://doi.org/10.1038/s41467-025-63236-1