Furthering understanding into the links between inflammation and depression, a new study has highlighted a fascinating association between white blood cell counts and genetic risk scores for depression. The study found even in the absence of depression symptoms someone with increased genetic susceptibility for depression will show higher white blood cell counts.
“We know that there’s a strong relationship between depression and several chronic health conditions, and we also know there’s a relationship between depression and inflammation,” explains Lea Davis, an author on the new study from the Vanderbilt Genetics Institute. “What we don’t know is exactly how they’re connected, which condition causes the other or if there’s something underlying that causes both.”
Whether or not there is a causal relationship between depression and inflammation is still of great debate amongst scientists. Many observational studies have reported correlations between biomarkers of inflammation and depression but some researchers suggest the relationship could be indirect. For example, poor sleep or obesity can be a result of depression while also causing low-grade inflammation.
So what comes first, depression or inflammation?
To investigate this question researchers looked at nearly 400,000 health records to study correlations between a person’s genetic risk for developing depression and white blood cell counts.
Also known as leukocytes, about one percent of our blood is made up of white blood cells. They are a crucial part of our immune system and high white blood cell counts can be a sign of our body fighting off an infection.
Across four different independent datasets the researchers found consistent associations between heightened white blood cell counts and polygenetic depression risk scores. This relationship was independent of any acute symptoms of depression.
“The relationship between depression polygenic scores and white blood cell count was statistically strong,” says Davis. “People with higher polygenic scores for depression had a higher white blood cell count, but the number was still considered in the ‘normal’ range. This suggests that sustained, but not abnormal, activation of the immune system may be contributing to depression.”
The research also indicates the relationship between depression and inflammation is likely to be bidirectional. This means it is unlikely for inflammation to be a singular cause of depression, but instead the data suggests a kind of feedback loop is at play. As depression develops, further biomarkers of inflammation can appear, and vice versa.
Julia Sealock, first author on the new study, says evidence is mounting to affirm the relationship between inflammation and depression, however, plenty more work is needed to unpack how this association works and whether it can lead to novel clinical treatments.
“I think our research contributes to mounting evidence of a pro-inflammatory state in depression and creates an exciting opportunity to think about a new class of anti-depressive therapies focused on lowering pro-inflammatory markers,” says Sealock. “We can now start asking if lowering pro-inflammatory markers leads to an anti-depressive effect. If so, this could bring about a paradigm shift in depression treatment from focusing on changing chemistry in the brain to changing biomarkers in the periphery.”
The new study was published in the journal JAMA Psychiatry.
