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By On March 19th, 2019

The mysterious link between depression and heart disease may be inflammation

The link between heart disease and depression has been well-known for years but has largely remained a mystery. All we have really known is that people with heart disease are more likely to live with depression, and those living with depression are more likely to develop heart disease.

Now, researchers at the University of Cambridge say they have uncovered the missing piece linking these two conditions – inflammation.

Inflammation is a natural response to a wide variety of negative factors, including stress, injury, and even physical inactivity. At normal levels, inflammation can be an essential step in healing injuries and fighting off dangerous bacteria or viruses.

At heightened levels, however, chronic inflammation can be harmful to the body.

Notably, inflammation is significantly related to both heart disease and depression.

“It is possible 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,” says Dr. Golam Khandaker, a Wellcome Trust Intermediate Clinical Fellow at the University of Cambridge. “Our work suggests that inflammation could be a shared mechanism for these conditions.”

For the study, published recently in the journal Molecular Psychiatry, Dr. Khandaker and study co-author Dr. Stephen Burgess led a group of researchers in reviewing data from bearly 370,000 middle-age individuals who participated in the UK Biobank.

The first factor the team investigated was whether a person’s family history of coronary heart disease was closely linked with their risk of major depression. Through this, they discovered that people who reported having at least one parent die from heart disease were 20% more likely to develop depression in their lifetime.

From there, the researchers created a genetic risk score for coronary heart disease designed to take into account the wide variety of genetic risk factors which contribute to heart disease. This allowed them to compare the genetic risk of heart disease and developing depression.

Notably, the researchers say there was no strong link between a genetic predisposition for heart disease and the risk of developing depression.

Taken together, these two findings are illuminating. They show that there is no genetic link between depression and heart disease. Rather, the link between the two conditions is being triggered by something in an individual’s environment – such as behavioral risk factors like smoking, substance abuse, or physical inactivity.

With this in mind, the team went in search of biomarkers which are associated with increased risk for coronary heart disease. They found 15 such biomarkers.

Through a process called Mendelian randomization, the researchers were then able to narrow down these biomarkers to just three which could also be linked to depression – triglycerides (which are a type of fat found in blood), and the proteins IL-6 and CRP.

Both IL-6 and CRP are inflammation-related proteins triggered by damage to the body, such as infection, stress or smoking. They have also been found in heightened levels in people with clinical depression – particularly in those with treatment-resistant depression.

This leads Dr. Khandaker to believe anti-inflammatory drugs – which have shown promise in clinical trials for treating depression – could be essential in directly addressing these inflammation-related factors.

Meanwhile, the link between triglycerides, coronary heart disease, and depression is less clear. It has been well-documented that high levels of triglycerides can contribute to heart disease, it is not known how this could also trigger depression. The researchers say the connection is not likely to be related to obesity, though, as they were unable to find evidence for a connection between body mass index (BMI) and depression.

“Although we don’t know what the shared mechanisms between these diseases are, we now have clues to work with that point towards the involvement of the immune system,” says Dr. Burgess. “Identifying genetic variants that regulate modifiable risk factors helps to find what is actually driving disease risk.”

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