More depressed patients than previously estimated may have increased activation of their immune systems

New research from the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at King’s College London has used an assessment of gene expression involved in the immune response to show that there may be more major depressive disorder (MDD) patients with activated immune systems than research has previously estimated.

By identifying the molecular mechanisms involved in this association, the research could pave the way for better identifying those patients with an immune component to their depression that could potentially help provide more personalized approaches to the treatment and management of major depressive disorder.

The research, published in Translational psychiatry it builds on previous findings that there is an activated immune response in many people with major depressive disorder.

However, most research in this area has focused on levels of inflammation-related proteins such as C-reactive protein (CRP). Studies using CRP have found that approximately 21-27% of depressed people have an activated immune response, but CRP levels don’t capture the full picture of the immune response. This new study set out to look at broader immune characteristics that are not captured by CRP levels.

168 participants were from the Biomarkers in Depression Study (BIODEP). 128 of them had a confirmed diagnosis of MDD and were then divided into three subgroups based on their blood CRP levels.

The researchers analyzed the expression of 16 genes whose activation is involved in the immune response. Gene expression is the initial stage in the process by which the information in our genes influences our characteristics and behavior. The initial analysis found higher expression of immune-related genes in people with MDD than in those without a diagnosis of depression.

When comparing MDD patients who had and did not have elevated blood CRP levels, there were no differences in the expression of these 16 genes, suggesting that this expression pattern was independent of CRP levels and potentially underlies a different mechanism.

Importantly, the researchers then conducted a secondary analysis on all those participants (both with and without a diagnosis of MDD) who had CRP values ​​below 1, meaning they are not considered to have any inflammation. The researchers found that participants with MDD and low CRP levels still had significantly higher expression of immune genes than those without a diagnosis of depression.

Professor Carmine Pariante, professor of biological psychiatry at King’s IoPPN and senior author of the study, said: ‘Previous research in this field has focused significantly on C-reactive protein (CRP) levels within people with the disorder major depressive disorder, which is a known marker of inflammation but only part of the immune response.”

“Our study has successfully expanded this focus and demonstrated that there is an immune response in the genes of those with MDD that is independent of CRP levels and importantly also in those in whom inflammation is not captured by measuring CRP. This means that increased immune system activation is present in many more depressed patients than originally thought.”

“These important findings will allow us to identify the molecular pathways involved in depression and also help more accurately identify those who have different types of immune responses which could pave the way for more personalized approaches to treatment.”

Dr. Luca Sforzini, first author of the King’s IoPPN study, said: ‘These evidence helps strengthen our understanding of immune-related depression. In particular, people with depression and immune impairments are less likely to respond to standard antidepressant medications and may benefit from specific interventions targeting the immune system.”

“I hope these findings will help current and future research better characterize individuals with depression based on their immunobiological profiles, offering more effective clinical strategies to large numbers of people who do not benefit from current antidepressants.”

The evidence of an immune-related predisposition in people with depression, independent of their routinely measured levels of inflammation, may extend our concept of immune-related depression.