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New research shows why depression treatments affect women differently than men

SHARE New research shows why depression treatments affect women differently than men
Alexia Williams uses a microscope to examine mouse brains in which RGS2 protein was experimentally increased.

Alexia Williams uses a microscope to examine mouse brains in which RGS2 protein was experimentally increased. Increasing the RGS2 protein in the nucleus accumbens reduced the effects of stress on behavior in female mice.

JR Martinez, University of California, Davis

Scientists found one reason why women and men respond differently to depression treatments. Researchers at the University of California, Davis say the answer may be in the brain.

While treatments for depression are available, they don’t work the same for everyone. Women experience higher rates of depression than men, yet the cause for this difference has been unknown, resulting in many women being unsuccessfully treated.

Researchers at UC Davis teamed up with scientists from Mount Sinai Hospital, Princeton University and Laval University, uncovering one reason why depression treatments may not affect women the same as men.

The nucleus accumbens is a part of the brain that controls motivation. Researchers compared samples of the nucleus accumbens in mice and humans to investigate how this part of the brain is affected by stress and depression in males and females.

The researchers studied mice that had experienced negative social interactions, which induce stronger depression-related behavior in females than males.

“These high-throughput analyses are very informative for understanding long-lasting effects of stress on the brain. In our rodent model, negative social interactions changed gene expression patterns in female mice that mirrored patterns observed in women with depression,” doctoral researcher Alexia Williams said.

Their studies of the nucleus accumbens show that different genes were turned on or off in women, but not in men diagnosed with depression. These changes could have caused symptoms of depression, or the depression experience could have changed the brain.

Researchers found this to be a clue as to why antidepressants had not been successful for some women.

“This is exciting because women are understudied in this field, and this finding allowed me to focus my attention on the relevance of this data for women’s health,” Williams said.

The study, “Comparative transcriptional analyses in the nucleus accumbens identifies RGS2 as a key mediator of depression-related behavior,” was published this month in the journal Biological Psychiatry.

After identifying similar molecular changes in the brains of mice and humans, researchers chose to manipulate the RGS2 gene. This gene controls the expression of a protein that regulates neurotransmitter receptors that are targeted by antidepressant medications like Prozac and Zoloft. “In humans, less stable versions of the RGS2 protein are associated with an increased risk of depression, so we were curious to see whether increasing RGS2 in the nucleus accumbens could reduce depression-related behaviors,” the author of the study, Brian Trainor, said.

When researchers increased RGS2 protein in the nucleus accumbens of the mice, they effectively reversed the effects of stress on the female mice, noting that social approach and preferences for preferred foods increased to levels observed in females that did not experience any stress.

“These results highlight a molecular mechanism contributing to the lack of motivation often observed in depressed patients. Reduced function of proteins like RGS2 may contribute to symptoms that are difficult to treat in those struggling with mental illnesses,” Williams said.

Williams said the team of researchers hopes to bring science one step closer to developing new treatments for those in need.