DNA Is Linked to Depression, but in Different Ways for Men and Women

There are exceptions to every rule. But science shows men and women tend to respond to depression differently. Women may express more stress and sadness, while men might show irritability and impulsive anger. How they react to antidepressants is also distinct: Although medication improves the symptoms of both groups, women are likelier to have a positive response.

Scientists want to know why this binary can emerge. Ultimately, a deeper understanding of sex differences can lead to better treatments for everyone.

And we are one step closer to this goal. In a study recently published in the journal Molecular Psychiatry, researchers pinpoint distinct biological differences between men and women to do with depression. They discovered that in the female participants, 11 areas of the genome were linked to depression. Among the males, only one area was linked to depression.

They also found that although depression affects how genes are expressed in both sexes in the same way, the molecular pathways are different in men and women.

These discoveries suggest “it is possible that certain drugs are more likely to benefit women and some other drugs are more likely to benefit men,” explains first author Patrícia Pelufo Silveira, an associate professor of psychiatry at McGill University, to Inverse. “This is still a matter to be researched, but our study opens a venue for this type of investigation.”

The link between depression and disease

The study’s findings are based on samples collected from 127,867 men and 146,274 women. Scientists analyzed their genetic data and responses to their questions about experiencing anxiety and depression.

Another critical finding that emerges from the study is that the genes related to depression in women are the same as those related to metabolic disease in women. Metabolic conditions can be present from birth or acquired and include conditions like Type 2 diabetes.

This discovery jibes with previous research, says Silveira. Metabolic alterations are prevalent in female patients that also have depression.

Silveira says this finding can help with the clinical management of depression in women, “confirming that metabolic diseases should be carefully investigated, prevented, and promptly treated, especially in this group.”

Improving treatments for depression

Silveira and her colleagues are hopeful that their findings will lead to meaningful change.

“We figured that if we had a better understanding of the biological mechanisms related to these differences that we see in the clinic, this could help us better manage the disease for both men and women,” she says.

While it’s known that men and women have different responses to treatment — women, for example, are more likely to find success with SSRI antidepressants, while men seem to benefit more from a different type of antidepressant called tricyclics — why this happens isn’t exactly clear. But it likely does come down to genetic differences, which are being illuminated in the work done by scientists like Silveira.

Beyond the question of why certain drugs work better for women than men is the question of why women are more than twice as likely to be diagnosed with depression than men. Part of this answer may stem from the reality that women are more likely to seek and receive mental health treatments. Socioeconomic factors may also explain why depression is more prevalent in women.

But men are also more likely to die by suicide, and sex differences in depression are generally understudied. There is more to learn — and this acquirement of new knowledge is likely to lead to improved mental health for all.