A wiring diagram of a human brain.
Illustration: NIH

There may not be a single depression gene, but there’s no question that our genetic makeup is an important factor in whether or not we get depressed. And our sex, it turns out, can be a factor in how those genes are expressed. In men and women diagnosed with major depressive disorder, the same genes show the opposite changes. In other words, the molecular underpinnings of depression in men and women may be different.

That’s according to a new postmortem brain study published on Wednesday in the journal Biological Psychiatry. The study could in the future help lead to more effective treatments for depression, if it turns out that men and women need different types of treatment.

To arrive at that conclusion, researchers at the University of Pittsburgh and Toronto’s Centre for Addiction and Mental Health analyzed gene expression levels in the postmortem brain tissue of 50 people who had major depressive disorder, of which 26 were men and 24 were women. (The data on their subjects was collected from several existing published data sets.) They also looked at the postmortem brain tissue of 50 men and women not diagnosed with depression. Gene expression levels are an indication of how much of a particular protein an individual gene is producing.

In the women with depression, they found that genes affecting synapse function were more expressed, meaning genes that play a role in how electrical activity is transferred between cells were producing more protein. In men, those same genes had decreased expression. In other genes with altered expression, a particular change occurred in only men or only women. Of 706 gene variants in men with depression and 882 variants in women with depression, 52 of the genes showed opposite changes in expression between the men and women. Only 21 genes changed in the same way in both sexes.

In the study, researchers focused on three regions of the brain that regulate mood: the dorsolateral prefrontal cortex, subgenual anterior cingulate cortex, and basolateral amygdala. To bolster their findings, they also looked at a smaller dataset of men and women with major depressive disorder and found similar results. More research, including studies in living patients, will be necessary to further validate the results.

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The study is significant for two reasons. For one, it is the first to suggest an opposing pathology for depression in men and women, which could eventually influence how depression is treated. Depression is complex disease that occurs in different regions of the brain, and increased understanding of the neurology and genetics of depression may lead to tailored depression treatments that are far more effective.

But the study also highlights the necessity of diversity in scientific study. Major depressive disorder affects women about twice as often as men. Women are also more likely to experience symptoms like weight gain along with depression, suggesting the biological mechanisms at work may be different. But many depression studies only look at men, and ones that look at both sexes do not necessarily differentiate between the two when reporting findings.

The science of genetics overwhelmingly suggests how similar we all really are. But it also underscores how much there is to gain from understanding and embracing how we are different.

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