Research Finds More Depressed Individuals With Activated Immune Systems Than Expected

A latest study conducted by King's College London's IoPPN indicates that the number of major depressive disorder (MDD) patients with activated immune systems might exceed previous estimations. By unraveling the molecular processes involved, this research has the potential to improve the identification of MDD patients with immune-related depression, enabling personalized treatment approaches.

The research, published in Translational Psychiatry and funded by the National Institute for Health and Care Research (NIHR) Maudsley Biomedical Research Centre (BRC) and a Wellcome Trust strategy award, builds on previous findings that there is an activated immune response in many people with MDD.

New Study Examines Broader Immune Characteristics Beyond CRP

However, most of the research in this area has focussed on the levels of inflammation related proteins like C-reactive protein (CRP). Studies using CRP have found that about 21 to 27 % of people with depression have an activated immune response1 but CRP levels do not capture the complete picture of the immune response. This new study set out to observe broader immune related characteristics that are not captured by CRP levels.

As many as 168 participants were sourced from the Biomarkers in Depression Study (BIODEP). A total of 128 of them had a confirmed diagnosis of MDD and they were then divided into three subgroups according to their levels of CRP in the blood.

Researchers analysed the expression of 16 genes whose activation is involved in the immune response. Gene expression is the initial stage of the process by which the information present in our genes influences our features and behaviour. The initial analysis found increased expression of immune-related genes in people with MDD compared to the those without a diagnosis of depression. When comparing MDD patients who did and didn’t have elevated levels of CRP in their blood, there were no differences in the expression of these 16 genes, suggesting this pattern of expression was independent of CRP levels and potentially underlying a different mechanism.

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

Study may Lead to Personalized Depression Treatment Approaches

Professor Carmine Pariante, Professor of Biological Psychiatry at King’s IoPPN and the study’s senior author said, “Previous research into this field has had a significant focus on C-reactive protein (CRP) levels within people with MDD which is a known marker for inflammation but just part of the immune response. Our study has successfully broadened this focus and shown that there is an immune response in the genes of those with MDD that is independent of CRP levels and, crucially, even in those where inflammation is not captured by measuring CRP. This means that increased immune 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 to more accurately identify those who have different types of immune responses which could pave the way for more personalised approaches to treatment.”

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Dr Luca Sforzini, the study’s first author from King’s IoPPN said, “This evidence contributes to strengthen our knowledge on immune-related depression. Notably, people with depression and immune alterations are less likely to respond to standard antidepressant medications and may benefit from specific interventions targeting the immune system. I am hopeful these findings will aid current and future research in better characterizing individuals with depression based on their immunobiological profiles, offering more effective clinical strategies to a large number of people who are not benefitting from current antidepressants.”

The evidence of an immune related predisposition in people with depression irrespective of their levels of inflammation as routinely measured can extend our concept of immune related depression.

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This work was supported by the National Institute for Health and Care Research (NIHR) Maudsley Biomedical Research Centre (BRC) and a Wellcome Trust strategy award to the Neuroimmunology of Mood Disorders and Alzheimer’s Disease (NIMA) Consortium.


Source-Eurekalert