Researchers already recognized the link between depression and heart disease. However, until recently, the mechanisms explaining it remained a mystery. A new study reveals that stress-induced inflammation may explain why mental and cardiovascular health are so intimately related.

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Why are people with depression more likely to have heart disease?

Heart disease is now the leading cause of death both in the United States and worldwide.

Depression, meanwhile, is the “leading cause of disability worldwide,” as well as one of the most common mental health conditions in the U.S.

A significant body of research has established a connection between the two conditions.

For example, reviews of existing studies have shown that people with cardiovascular disease are more likely to have depression, and people with depression have a higher risk of developing cardiovascular disease.

Also, those with depression and heart disease are more likely to die from the latter than those who only have heart disease. This relationship is also proportional, meaning that the more severe the depression, the more likely it is that a person will develop heart disease or die from it.

What explains this link? Researchers from the University of Cambridge in the United Kingdom set out to investigate. Golam Khandaker, a Wellcome Trust Intermediate Clinical Fellow at the University of Cambridge, led the new research with his colleague Stephen Burgess.

The researchers published their findings in the journal Molecular Psychiatry.

The team examined data on almost 370,000 people aged 40–69. The data were readily available in the UK Biobank database.

They first wanted to see whether having a family history of coronary heart disease also increased the risk of major depression, and they found that it did.

In fact, people who had lost at least one parent to heart disease had a 20 percent higher risk of depression.

Next, the scientists wondered whether genes determined this link. They calculated the genetic risk score for coronary heart disease but found no connection between the genetic predisposition to develop heart disease and the risk of depression.

This suggested to the scientists that depression and heart disease do not share a common genetic predisposition. Instead, they wondered whether there were any environmental factors that may raise the risk of developing both conditions.

To find out, they applied a statistical tool called Mendelian randomization to examine 15 biological markers, or biomarkers, that may affect heart disease risk.

Scientists use this technique “to assess the causality of an observed association between a […] risk factor and a clinically relevant outcome.”

Their analysis revealed three biomarkers for the risk of heart disease that were also depression risk factors: triglycerides and the inflammation-related proteins IL-6 and CRP.

The scientists explain that our bodies produce the inflammation proteins IL-6 and CRP in response to physiological factors such as infections and lifestyle factors such as smoking, drinking, and physical inactivity, as well as in response to psychological stress.

High inflammation markers are often present in treatment-resistant depression, and high levels of IL-6 and CRP in particular often characterize acute depressive episodes.

Also, previous studies the researchers cited have shown that people with high levels of IL-6 and CRP are more likely to develop depression.

“It is possible,” Khandaker points out, “that heart disease and depression share common underlying biological mechanisms, which manifest as two different conditions in two different organs — the cardiovascular system and the brain.”

Our work suggests that inflammation could be a shared mechanism for these conditions.”

Golam Khandaker

However, the researchers caution that more work is now necessary. They also note that the role of triglycerides in depression risk has yet to be understood.

“Although we don’t know what the shared mechanisms between these diseases are, we now have clues to work with that point toward the involvement of the immune system,” says Burgess.

“Identifying genetic variants that regulate modifiable risk factors,” he goes on, “helps to find what is actually driving disease risk.”