New Study Reveals Higher Prevalence of Immune Activation in Depression
Recent research conducted at the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at King’s College London indicates that immune system activation in individuals with Major Depressive Disorder (MDD) may be more common than previously believed. Interestingly, this immune activation appears to be independent of inflammation levels as measured by C-reactive protein (CRP). This groundbreaking discovery has the potential to deepen our understanding of the molecular pathways associated with depression, leading to more personalized treatment options, particularly for patients who do not respond well to standard antidepressant medications due to immune alterations.
The study, published in Translational Psychiatry and financially supported by the National Institute for Health and Care Research (NIHR) Maudsley Biomedical Research Centre (BRC) and a Wellcome Trust strategy award, builds upon previous findings indicating the presence of an activated immune response in many individuals with MDD.
While previous research in this field has primarily focused on measuring inflammation-related proteins like CRP, which revealed an activated immune response in approximately 21 to 27% of individuals with depression, this study sought to explore broader immune-related characteristics not captured by CRP levels.
The researchers examined 168 participants from the Biomarkers in Depression Study (BIODEP), of which 128 had a confirmed diagnosis of MDD. These participants were divided into three subgroups based on their CRP levels in the blood.
By analyzing the expression of 16 genes involved in immune response activation, the researchers observed increased expression of immune-related genes in individuals with MDD compared to those without a depression diagnosis. Notably, when comparing MDD patients with and without elevated CRP levels, no differences were found in the expression of these 16 genes. This suggests that the observed pattern of gene expression is independent of CRP levels and may involve an alternative mechanism.
Significantly, a secondary analysis was conducted on all participants (with or without a diagnosis of MDD) whose CRP values were below 1, indicating no inflammation. Even among these participants with low CRP levels, those with MDD exhibited significantly higher expression of immune genes compared to individuals without a depression diagnosis.
Professor Carmine Pariante, the senior author of the study and a Professor of Biological Psychiatry at King’s IoPPN, stated, “Previous research in this field has predominantly focused on C-reactive protein (CRP) levels in individuals with MDD, which is a recognized marker for inflammation but only a part of the immune response. Our study has expanded this focus and demonstrated that individuals with MDD show immune response in their genes that is independent of CRP levels and, importantly, even in cases where CRP fails to detect inflammation. This implies that increased immune activation is present in a larger number of depressed patients than previously believed.”
“These significant findings will help us identify the molecular pathways implicated in depression and improve our ability to identify individuals with distinct immune responses. Ultimately, this could pave the way for more personalized treatment approaches,” added Professor Pariante.
Dr. Luca Sforzini, the study’s first author from King’s IoPPN, commented, “This evidence contributes to our understanding of immune-related depression. Notably, individuals 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 that these findings will support ongoing and future research efforts to better characterize individuals with depression based on their immunobiological profiles, ultimately offering more effective clinical strategies to a large number of people who currently do not benefit from existing antidepressants.”
The study’s findings indicate the presence of an immune-related predisposition in individuals with depression, regardless of their inflammation levels as conventionally measured, expanding our understanding 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 received funding from 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.
Table of Contents
Frequently Asked Questions (FAQs) about immune activation in depression
What does the new study suggest about immune activation in depression?
The new study suggests that immune activation in individuals with Major Depressive Disorder (MDD) may be more prevalent than previously thought, independent of inflammation levels measured by C-reactive protein (CRP).
How can this study contribute to the understanding of depression?
This study can contribute to a better understanding of the molecular pathways involved in depression by identifying the immune-related genes associated with the condition. It broadens the focus beyond inflammation levels and provides insights into personalized treatment approaches.
Why is immune activation important in depression?
Immune activation is important in depression because individuals with immune alterations are less likely to respond to standard antidepressant medications. Identifying the immune-related aspect of depression can help develop specific interventions targeting the immune system for more effective treatment.
How was the study conducted?
The study analyzed gene expression of 16 immune-related genes in 168 participants with and without a diagnosis of MDD. The participants were divided into subgroups based on their levels of CRP in the blood. The expression of these genes was compared between individuals with and without depression, as well as between those with different CRP levels.
What were the main findings of the study?
The study found increased expression of immune-related genes in individuals with MDD compared to those without depression, regardless of their CRP levels. This suggests that immune activation is present in many depressed patients, even when inflammation is not detected by CRP measurement.
How was the study funded?
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.
More about immune activation in depression
- Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at King’s College London: Website
- Translational Psychiatry: Journal
- National Institute for Health and Care Research (NIHR): Website
- Wellcome Trust: Website
- Neuroimmunology of Mood Disorders and Alzheimer’s Disease (NIMA) Consortium: Website
3 comments
thx 4 the info! i didn’t know about the link between immune activation and depression. it’s good they found this out cuz now we can help those who don’t benefit from regular antidepressants. really important work!
wow, this study showz immune activation in depression! sooo important. it can help with better treatments for ppl who no respond to normal meds. amazing research!
i luv that they look at gene expression and not just the inflammation markers. depression is complex, and this studie finds more ppl with immune activation. need more personalized care options!