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People with depression have higher levels of inflammation in their bodies than those who don鈥檛 have the condition, but it is unclear whether this is due to genes that indicate a predisposition for depression, or because depression can lead to behaviours that trigger inflammation.

at King鈥檚 College London and her colleagues used data from the UK Biobank, which holds medical and genetic information on half a million people, to investigate this link. They compared 26,894 people who had been diagnosed with depression at some point in their lives with 59,001 people with no previous history of the condition.

The team analysed blood samples, genetic data and responses to physical and mental health questionnaires, and found that the people who had been diagnosed with depression had higher levels of C-reactive protein (CRP) in their blood, a marker for inflammation in the body. This was true even for some participants who had been previously diagnosed with depression, but who weren鈥檛 experiencing the condition when their blood samples were taken.

On average, people who had received a diagnosis of depression had CRP levels of 2.4 milligrams per litre compared with 2.1 mg/L in those with no diagnosis, while 21.2 per cent of people with depression had CRP levels greater than 3 mg/L, compared with 16.8 per cent of people with no diagnosis.

鈥淭here are many people with higher levels of inflammation who have not been diagnosed with depression, but there鈥檚 clearly an association there,鈥� says Lewis.

The team also looked at body mass index (BMI), smoking, alcohol consumption and other lifestyle habits and found that these factors only partially contributed to increased inflammation, suggesting another factor, possibly genetic, was at work.

Identifying such a link is difficult because there are many genetic influences on depression. 鈥淲e鈥檝e made great progress in identifying the genetic component of depression and many other disorders,鈥� says Lewis. 鈥淲e鈥檙e not just looking at a single gene or a single genetic variant, but we鈥檙e looking at hundreds or thousands of genetic variants across the genome.鈥�

The researchers assigned each person in the study with a polygenic risk score, summarising their genetic links to depression. They then tested whether people with higher risk scores, who have a higher genetic risk of depression, also had higher levels of CRP.

Initially they found a link, but after correcting for the effect of smoking and BMI on inflammation, this association disappeared, says Lewis.

鈥淲e know that people with depression are more likely to smoke than people without depression and we know that people with depression have a higher body mass index than those without. And so, all these factors 鈥� inflammation, genetics of depression, body mass index and smoking 鈥� are sort of tied up together,鈥� she says.

鈥淭hese analyses showed that CRP was associated with depression. This is an important finding. However, unanswered is how clinically significant the difference in CRP between depressed and non-depressed people is,鈥� says at the University of Texas Southwestern Medical Center.

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