Major depressive disorder (MDD) and inflammation were discovered to be significantly correlated in a recent ground-breaking study published in September 2024. Researchers from Italy and King's College London, UK concentrated the study on the functions of cell-cycle related pathways and immunometabolic mechanisms behind the pathophysiology of MDD. The results and implications of this study were thoroughly analyzed in a recent Neuroscience News article.
In depression, as in almost every medical condition, one size does not fit all. Understanding the diversity of people with depression means also recognizing the different biological patterns in action.
Dr. Luca Sforzini, King's College London.
The study focused on whole-transcriptome and pathway analyses on 139 individuals from the observational, case-control, BIOmarkers in DEPression (BIODEP) study, 105 with MDD and 34 controls.
Researchers divided MDD participants based on exposure and response to antidepressants and identified specific immunomodulatory and neuroprotective pathways in responders (especially vs. non-responders). They found that even moderate levels of inflammation led to a significant increase in immune-related gene activity, while those with severe inflammation experienced additional metabolic gene activation. This points to a possible connection between the body's immunological response and elevated levels of inflammation associated with depression.
With gene expression, we might capture something different from what is clinically observable, something ‘intermediate’ between what’s encoded in our genes and what is ultimately manifested.
Professor Annamaria Cattaneo
The study further revealed a unique gene expression profile involving mechanisms that not only reduced immune system activation but also promoted brain protection in antidepressant-responsive patients, thus paving way for anti-inflammatory medications as possible additions to conventional therapies. These findings broaden our understanding on the working mechanism of antidepressants and how different types of depression are treated. The outcomes of this study facilitate a precision-medicine approach to MDD and provide hope to patients with treatment resistant depression.
Our research highlights the need to understand the biological basis of different types of depression, shifting away from the traditional approach, towards more targeted and personalized approaches
Professor Carmine Pariante
https://doi.org/10.1038/s41380-024-02736-w
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