Researchers Uncover Why Depression is Harder to Treat in Women

By Lauren DeSouza- Master of Public Health, Simon Fraser Public Research University – Canada
Staff Research and Content Writer

This article is reproduced herein with permission of the copyright holder.

© Copyright – SUD RECOVERY CENTERS – A Division of Genesis Behavioral Services, Inc.,
Milwaukee, Wisconsin – August 2022 – All rights reserved.

Women are twice as likely to develop depression compared to men. Treatments for depression, such as antidepressant medication, are often not as effective for women.  Scientists have not yet been able to identify the reasons for these sex-specific differences. Studies on depression often focus on male subjects, which limits our understanding of depression in females, which hinders efforts to effectively treat women with depression.  

Researchers are now prioritizing evidence that will improve understanding of how depression works in women.  A new study identifies a potential reason antidepressant medications have been less effective among women, opening the door to create new, more effective treatments.

How did this study work?

There is a specific region of the brain that behaves differently in people with depression compared to the rest of the population. This region of the brain, the nucleus accumbens (NAc), plays a role in motivation, response to rewarding experiences, and social interactions. People with depression often experience symptoms relating to these areas. Recent research suggests that the NAc works differently in women with depression compared to men. Specifically, some genes in the NAc are turned on and off in women with depression, but not in men.  

This study examined the NAc in female mice to understand how the NAc functions in the brains of women with depression. Since stress and social interactions affect the NAc, researchers exposed the mice to negative social interactions. This induced depression-like behavior and enabled the researchers to see more clearly how this region of the brain works in female subjects.

What did this study find?

The researchers Identified a gene, Rgs2, that is altered in females but not in males with depression. Females experiencing stress (related to depression) had decreased levels of Rgs2. Rgs2 controls the expression of a protein that regulates neurotransmitter receptors that are targeted by antidepressant medications such as Prozac and Zoloft. When Rgs2 is low, risk of depression is higher. 

Rgs2 is responsible for regulation of neurotransmitter receptors that are targeted by antidepressant medications such as Prozac or Zoloft. Low Rgs2 expression may impact control of these receptors and partly explain why antidepressants are less effective in women.  

The researchers experimented with Rgs2 by increasing it in the NAc of female mice. Doing so reversed the effects of stress on the mice and alleviated some depression symptoms such as low motivation and poor appetite. The researchers believe that this gene, Rgs2, can be utilized to develop therapeutic treatments specifically for women experiencing depression.

What were the conclusions of the study?

This study identified a gene that behaves uniquely in females experiencing depression symptoms. The findings suggest that manipulating Rgs2 can change depression-related behavior and the symptoms of depression that women experience. The researchers recommend that future studies focus on identifying specific mechanisms that increase and decrease Rgs2 expression in order to develop pharmacological treatments for women with depression.

Key Points

  • Women experience depression at a higher rate than men and benefit less from existing treatments.
  • There is a region of the brain that behaves differently among women with depression compared to men. This region governs expression of a gene targeted by antidepressants, Rgs2.
  • There may be a way to control or increase gene expression of Rgs2 to help make treatments more effective in women. 
  • More research is needed to inform the development of depression treatments for women that make use of the Rgs2 gene.


Alexia V. Williams, Catherine J. Peña, Stephanie Ramos-Maciel, Abigail Laman-Maharg, Evelyn Ordonez-Sanchez, et al. Comparative transcriptional analyses in the nucleus accumbens identifies RGS2 as a key mediator of depression-related behavior, Biological Psychiatry, 2022, ISSN 0006-3223,

University of California – Davis. “Scientists pinpoint reason why women may not respond to depression treatments the same as men.” ScienceDaily. ScienceDaily, 13 July 2022. <>.