A team of scientists at King’s College London investigated the pathways — genetic, environmental, lifestyle, medical — leading to inflammation in major depressive disorder using data from the UK Biobank.
C-reactive protein, a marker for inflammation in the body, was found in higher levels in depressed people compared to non-depressed people. Image credit: Jawahar Swaminathan & MSD staff, European Bioinformatics Institute.
“Our study highlights how genetics can be used as a tool for dissecting mental health disorders,” said Professor Cathryn Lewis, a researcher at the Institute of Psychiatry, Psychology & Neuroscience at King’s College London.
Professor Lewis and colleagues used the largest ever community-based sample with information on mental health, inflammation, genome-wide association study (GWAS) data linking genes to certain diseases, environment, lifestyle and physical health with 85,895 participants.
The researchers analyzed blood samples, genetic data and physical and mental health questionnaires collected by UK Biobank.
Of the 85,895 participants, around 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 scientists 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 liter.
Inflammation is a biological response which is predominantly directed to fight infection but also has an important role in regulating behavior. 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 authors found that the greater the genetic risk for depression, the greater the level of inflammation.
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.
“Our study provides the most conclusive evidence to date that people with depression have proteins in their blood indicating activation of the inflammatory system,” said Dr. Maria Pitharouli, also from the Institute of Psychiatry, Psychology & Neuroscience at King’s College London.
“Furthermore, through in-depth analysis we have discovered more about the mechanisms that may be behind the relationship between inflammation and depression.”
“Here we’ve shown that the genetic contribution to inflammation in depression comes mostly from eating and smoking habits,” Professor Lewis said.
“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.”
“We show that there may be a core biological process that is behind the association between depression and increased inflammation,” said Professor Carmine Pariante, a researcher at the National Institute for Health Research Maudsley Biomedical Research Centre.
“If we can identify this process and uncover more detail about its role in the development of depression, we can pave the way for trialing new treatments for this widespread mental health disorder.”
The study was published in the American Journal of Psychiatry.
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Maria C. Pitharouli et al. Elevated C-Reactive Protein in Patients With Depression, Independent of Genetic, Health, and Psychosocial Factors: Results From the UK Biobank. American Journal of Psychiatry, published online May 14, 2021; doi: 10.1176/appi.ajp.2020.20060947