THE ESSENTIAL
- A meta-analysis shows that healthy people given low doses of immunostimulating agents develop temporary depressive symptoms.
- Stress-related inflammatory responses can trigger the brain’s immune cells, but prolonged stress eventually depletes and damages them, maintaining or worsening depression.
- These results indicate that a personalized approach to treatment, i.e. “based on the patient’s specific inflammatory profile”, may prove more effective than a single traditional antidepressant treatment.
Over the past 30 years, substantial evidence has accumulated supporting the hypothesis that dysregulation of inflammatory processes plays a critical role in the pathophysiology of depression. Professor Raz Yirmiya was one of the first researchers to establish associations between immune system dysfunction and depression in the 1990s.
Depression: a mechanical link between inflammation and mood
As part of his latest study, he retraced the evolution of research highlighting this link, discussing key results: “alterations in inflammatory markers associated with depression, mood changes following exogenous administration of inflammatory challenges, anti-inflammatory properties of traditional antidepressants, and promising antidepressant effects of anti-inflammatory medications.” Additionally, the scientist explored how inflammatory processes interact with specific brain regions and neurochemical systems to lead to depressive disorder.
For the purposes of this work, published in the journal Brain, Behavior, and Immunitythe professor and his team reviewed 100 of the most cited experimental studies on the subject, creating what he calls a “panoramic view” complex interactions between inflammation and depressive symptoms. The analysis established a mechanistic link between inflammation and mood, showing that healthy people injected with low doses of immunostimulating agents experienced temporary depressive symptoms. This state could be avoided by anti-inflammatory treatments or classic antidepressants.
Prolonged stress can deplete brain immune cells
Another observation: inflammatory responses linked to stress, which is often one of the main triggers of depression, can initially activate microglia (namely a population of cells of the innate immune system, specific to the central nervous system). However, prolonged stress ends up exhausting and damaging it, which maintains or worsens depression. “This dynamic cycle of microglia activation and degeneration reflects the progression of depression itself,” said Raz Jeremiah.
The study also found cohorts that suggest that specific groups, such as the elderly, adults with physical illnesses, patients who suffered childhood adversity, and patients with treatment-resistant depression, were particularly likely to suffer from inflammation-related depression.
Depression: “adapt the treatment according to the patient’s specific inflammatory profile”
According to the authors, these data reveal the need for anti-inflammatory treatments for some patients and microglia-stimulating treatments for others. “In the future, a personalized medicine approach, that is, tailoring treatment according to the patient’s specific inflammatory profile, offers hope to millions of sufferers who find little relief in standard therapies “By adopting these advances, we are not just treating the symptoms, we are addressing the underlying causes.” concluded the professor.
