Research from the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at King’s College London suggests that the prevalence of immune system activation in patients with Major Depressive Disorder (MDD) could be higher than previously thought, with this activation being independent of inflammation levels as measured by C-reactive protein (CRP). This discovery could lead to a better understanding of the molecular pathways involved in depression, enabling more personalized treatment approaches, particularly for those patients who don’t respond well to standard antidepressant medications due to these immune alterations.
New findings from the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at King’s 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 aspect. This could pave the way for more personalized treatment and management strategies for MDD, enhancing overall patient care.
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.
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.
168 participants were sourced from the Biomarkers in Depression Study (BIODEP). 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 analyzed 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 behavior. The initial analysis found increased expression of immune-related genes in people with MDD compared to 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.
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 personalized approaches to treatment.”
Dr Luca Sforzini, the study’s first author from King’s IoPPN said, “This evidence contributes to strengthening 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.
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 and Alzheimer’s 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 Alzheimer’s Disease (NIMA) Consortium.
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