Inflammation is a core feature of depression: new evidence from large-scale study

People with depression have higher levels of inflammation in their bodies than those without depression, regardless of socioeconomic background, ill health or unhealthy behaviours, a study by King’s College London finds.

C-reactive protein (CRP), a marker for inflammation in the body, was found in higher levels in depressed people compared to non-depressed people in the largest ever study into the genetic, environmental, lifestyle, medical pathways leading to inflammation in major depressive disorder (MDD).

The effect was reduced but remained significant when factors known to be related to increased inflammation such as smoking, body mass index (BMI) and trauma were taken into account, adding to the body of evidence that there may be a direct biological link between inflammation and depressive disorders. The study was conducted by researchers funded by the NIHR Maudsley Biomedical Research Centre and NARSAD (National Alliance for Research on Schizophrenia & Depression) and it was published in the American Journal of Psychiatry.

Using 86,000 participant's data

Researchers analysed blood samples, genetic data and physical and mental health questionnaires collected by UK Biobank, the large-scale biomedical database and research resource with over half a million UK participants who were recruited between in 2006-2010. Of the 86,000 participants included in the study just under a third (31%) were classified as having major depressive disorder. This percentage is similar to estimates found by other studies on the global prevalence of depression occurring during a person’s lifetime.

The study showed that depressed participants had raised C-reactive protein (CRP) levels in their blood compared to non-depressed participants, and were more likely to have low-grade inflammation, defined as CRP levels in the blood of over 3 mg per litre. Inflammation is a biological response which is predominantly directed to fight infection but also has an important role in regulating behaviour. CRP is one marker for inflammation.

Further analysis showed that this increased inflammation in depression is only partially explained by clinical and sociodemographic factors including age, sex, body mass index (BMI) smoking, alcohol consumption, exposure to early life trauma, socio-economic status and self-reported health status.

The study found that the greater the genetic risk for depression, the greater the level of inflammation.

Polygenic risk scores

The polygenic risk score gives an estimate of how likely an individual is to have a given trait based only on genetics. The researchers calculated polygenic risk score in participants for major depression was strongly associated with levels of CRP. However, this association was no longer present when BMI and smoking were taken into account. In contrast, polygenic risk scores for three immune disorders - biliary cirrhosis, Crohn’s disease and rheumatoid arthritis- are all positively associated with CRP levels even after controlling for BMI and smoking.

Hear from the authors

First author Maria Pitharouli, Research Associate at the Institute of Psychiatry, Psychology & Neuroscience, King’s College London said:

“Our study provides the most conclusive evidence to date that people with depression have proteins in their blood indicating activation of the inflammatory system. Furthermore, through in-depth analysis of data from over 86,000 people we have discovered more about the mechanisms that may be behind the relationship between inflammation and depression.”

Joint senior author, Professor Cathryn Lewis who leads the Social, Genetic and Developmental Psychiatry Centre at the Institute of Psychiatry, Psychology & Neuroscience, King’s College London said:

“Our study highlights how genetics can be used as a tool for dissecting mental health disorders. Here we’ve shown that the genetic contribution to inflammation in depression comes mostly from eating and smoking habits. That finding is important to help us understand depression better - and one further piece in the jigsaw puzzle towards improving care for people with depression.”

Joint senior author, Professor Carmine Pariante from the National Institute for Health Research Maudsley Biomedical Research Centre said:

“Our large-scale analysis of data removed socioeconomic background, ill health, unhealthy habits as well as genetic predisposition to immune dysfunction as the only explanations for the relationship between depression and inflammation. By this process of elimination, we show that there may be a core biological process that is behind the association between depression and increased inflammation. If we can identify this process and uncover more detail about its role in the development of depression, we can pave the way for trialling new treatments for this widespread mental health disorder.”

The paper ‘Depressed patients have elevated c-reactive protein independently of genetic, health and psychosocial factors, in the UK Biobank’ was published today [Friday 14 May 2021] in the American Journal of Psychiatry.


To receive a copy of the embargoed paper or to arrange interviews please contact the Communications team at NIHR Maudsley BRC: 

  • Franca Davenport, Communications and Engagement Manager, NIHR Maudsley Biomedical Research Centre,
  • Serena Rianjongdee, Communications and Engagement Officer, NIHR Maudsley Biomedical Research Centre,

Tags: Publications - Affective Disorders and Interface with Medicine -

By NIHR Maudsley BRC at 14 May 2021, 08:01 AM

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