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Major depression: Brain tissue reveals sex-specific gene changes

Healthline/Medical News Today Mar 21, 2018

Men and women may each benefit from different treatments for depression. This is the conclusion of a new study published in the journal Biological Psychiatry, which identified opposing alterations in gene expression changes between men and women with the condition.

Major depression, or major depressive disorder, is a mental health disorder in which depressive symptoms persist for at least 2 weeks.

Such symptoms include continuous feelings of sadness, anxiety, hopelessness or guilt, loss of interest in activities and hobbies, lack of energy, and—in some cases—suicidal thoughts.

It is estimated that in 2016, around 16.2 million adults in the United States experienced at least one episode of major depression.

Such episodes were almost twice as common among women than men.

Given the difference in the prevalence of major depression between the sexes, scientists have investigated whether there might be distinctions in the molecular mechanisms that drive major depression in men and women.

One study that was reported last year identified different responses in the supramarginal gyrus and posterior cingulate cortex brain regions of male and female participants with depression.

In this latest study, lead author Dr. Marianne Seney, PhD, from the Department of Psychiatry at the University of Pittsburgh Medical School in Pennsylvania, and colleagues pinpointed specific genetic differences between men and women with major depression.

Results have 'significant implications'

The researchers came to their findings by analyzing brain tissue of 50 deceased adults who had major depression. Of these subjects, 26 were men and 24 were women.

Specifically, the researchers searched for genetic alterations across three brain regions. These regions were the dorsolateral prefrontal cortex, subgenual anterior cingulate cortex, and basolateral amygdala, all of which are implicated in depression.

For comparison, the team also studied the postmortem brain tissue of men and women without major depression.

The study identified 706 genes that were expressed differently in men with major depression and 882 genes that were expressed differently in women with the disorder.

Interestingly, of the few genes expression changes that were shared between men and women, the researchers identified just 21 genes that were altered in the same direction. Fifty-two gene expression changes that were shared between men and women were modified in different directions.

As an example, the researchers found that women with major depression showed an increase in the expression of genes that influence the function of synapses, which are structures that enable communication between neurons. But men with major depression showed a reduction in these same genes.

The authors also report that opposing gene expression changes were specific to the different brain regions. For example, if a woman with major depression showed an increase in the expression of a gene within a certain brain region, a man would show a reduction in the expression of this gene, and vice versa.

Dr. Seney and colleagues note that because their study looked at postmortem brain tissue, they were unable to assess whether the opposing gene expression changes they identified led to differences in how major depression affects men and women.

Still, they believe that their results suggest that men and women may require different treatment approaches for the disorder.

"These results have significant implications for development of potential novel treatments and suggest that these treatments should be developed separately for men and women."

Dr. Marianne Seney, PhD

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