Higher immune-related gene expression in major depression is independent of CRP levels: results from the BIODEP study, 2023, Pariante et el

Higher immune-related gene expression in major depression is independent of CRP levels: results from the BIODEP study
https://www.nature.com/articles/s41398-023-02438-x


Abstract (paragraphs mine)

Compelling evidence demonstrates that some individuals suffering from major depressive disorder (MDD) exhibit increased levels of inflammation. Most studies focus on inflammation-related proteins, such as serum or plasma C-reactive protein (CRP). However, the immune-related modifications associated with MDD may be not entirely captured by CRP alone. Analysing mRNA gene expression levels, we aimed to identify broader molecular immune-related phenotypes of MDD.

We examined 168 individuals from the non-interventional, case–control, BIODEP study, 128 with a diagnosis of MDD and 40 healthy controls. Individuals with MDD were further divided according to serum high-sensitivity (hs)CRP levels (n = 59 with CRP <1, n = 33 with CRP 1–3 and n = 36 with CRP >3 mg/L).

We isolated RNA from whole blood and performed gene expression analyses using RT-qPCR. We measured the expression of 16 immune-related candidate genes: A2M, AQP4, CCL2, CXCL12, CRP, FKBP5, IL-1-beta, IL-6, ISG15, MIF, GR, P2RX7, SGK1, STAT1, TNF-alpha and USP18. Nine of the 16 candidate genes were differentially expressed in MDD cases vs. controls, with no differences between CRP-based groups.

Only CRP mRNA was clearly associated with serum CRP. In contrast, plasma (proteins) IL-6, IL-7, IL-8, IL-10, IL-12/IL-23p40, IL-16, IL-17A, IFN-gamma and TNF-alpha, and neutrophils counts, were all differentially regulated between CRP-based groups (higher in CRP >3 vs. CRP <1 and/or controls), reflecting the gradient of CRP values.

Secondary analyses on MDD individuals and controls with CRP values <1 mg/L (usually interpreted as 'no inflammation') confirmed MDD cases still had significantly different mRNA expression of immune-related genes compared with controls. These findings corroborate an immune-related molecular activation in MDD, which appears to be independent of serum CRP levels.

Additional biological mechanisms may then be required to translate this mRNA signature into inflammation at protein and cellular levels. Understanding these mechanisms will help to uncover the true immune abnormalities in depression, opening new paths for diagnosis and treatment.

 

Article with summary explanation: https://scitechdaily.com/new-study-...mon-than-previously-thought/?expand_article=1.

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.
...
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.​

Of course it remains how valid the cohort is, depression has the same problem as ME in that lacking a test, cohorts can't be assumed to be homogeneous or representative. Still, when in doubt, the default explanation of medicine should have been immunological, rather than magical psychology, so long ago.

Yes, it's that Pariante.