New study: Immune activation in depression is more common than previously thought

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Research from the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at Kings College London suggests that the prevalence of immune system activation in patients with major depressive disorder (MDD) may be higher than previously thought, with this activation independent of inflammation levels as measured by C-reactive protein (CRP). This finding could lead to a better understanding of the molecular pathways involved in depression, allowing for more personalized treatment approaches, particularly for those patients who do not respond well to standard antidepressant medications due to these immune alterations.

New findings from the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at Kings College London suggest that the number of patients with major depressive disorder (MDD) who have activated immune systems may be greater than previously thought. This conclusion is based on an assessment of gene expression associated with the immune response.

By identifying the molecular mechanisms involved in this association, the study could potentially improve the identification of patients whose depression has an immune-related pattern. This could pave the way for more personalized treatment and management strategies for MDD, improving overall patient care.

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

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 response1, but CRP levels do not 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 major depressive disorder 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 mechanism different.

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 Kings IoPPN and senior author of the study said: “Previous research in this area has focused significantly on C-reactive protein (CRP) levels within people with MDD which is a known marker of inflammation but only part of the immune response. Our study successfully broadened 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 which 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 personalized approaches to treatment.

Dr. Luca Sforzini, lead author of the Kings IoPPN study, said: “This 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.

Reference: Higher immune-related gene expression in major depression is independent of CRP levels: results from the BIODEP study by Luca Sforzini, Annamaria Cattaneo, Clarissa Ferrari, Lorinda Turner, Nicole Mariani, Daniela Enache, Caitlin Hastings, Giulia Lombardo, Maria A. Nettis, Naghmeh Nikkheslat, Courtney Worrell, Zuzanna Zajkowska, Melisa Kose, Nadia Cattane, Nicola Lopizzo, Monica Mazzelli, Linda Pointon, Philip J. Cowen, Jonathan Cavanagh, Neil A. Harrison, Declan Jones, Wayne C. Drevets, Valeria Mondelli, Edward T. Bullmore, Neuroimmunology of mood disorders e[{” attribute=””>Alzheimers Disease (NIMA) Consortium and Carmine M. Pariante, 1 June 2023, Translational Psychiatry.
DOI: 10.1038/s41398-023-02438-x

The study was funded 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 Alzheimers Disease (NIMA) Consortium.