Depression Is Linked to Inflammation

Depression is one of the most common mental disorders—about 10% to 20% of the general population experiences a depressive episode in their lifetime.

Most scientific studies aimed at understanding how depression develops focus on the nervous system, for example how problems with serotonin and other neurotransmitters affect mood and behavior. In addition to those factors, it has recently been suggested that the immune system and its reaction to inflammation in the body might also affect depression.

A new study by Osimo et al. (2020) systematically investigated this question in a large cohort. The authors conducted a so-called meta-analysis. A meta-analysis is a form of statistical analysis that integrates the results of many different empirical studies. This has the advantage that the sample size is much larger, increasing statistical power and rendering the analysis less likely to be affected by cohort characteristics of individual studies. This way, the true direction and size of a statistical effect can be determined.

Meta-analyses are an important tool in psychology, and they're now used more and more, particularly in times in which many studies have been criticized for testing numbers of participants that are so small that it is almost impossible to draw any conclusions from the observed results.

What did the researchers exactly do?

The researchers searched scientific databases for studies that reported immune system marker levels in the blood of depressed patients and healthy controls. Overall, they identified 107 studies with a total number of 5,166 depressed patients and 5,083 healthy controls.

The following immune system parameters were analyzed in the blood of the patients and controls:

• Different forms of interleukins (IL): These molecules participate in immune system regulation and inflammatory reactions (the researchers investigated levels of IL-1 alpha, IL-1 beta, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, IL-18, sIL-1RA, sIL-2R, sIL-6R).
• Tumor necrosis factor-alpha (TNF alpha): This protein is involved in systematic inflammation.
• Interferon (IFN) gamma: This protein in the immune system is involved in fighting viruses.
• Transforming growth factor (TGF) beta: This polypeptide is involved in the regulation of the immune system.
• C-reactive protein (CRP): The concentrations of this protein in the blood plasma rises in response to inflammation.

In general, higher levels of these parameters signified a stronger immune system response and therefore higher levels of inflammation in the body.

What did they find out?

The results were striking. The researchers found that across all immune parameters, depressive patients had a higher mean concentration in their blood than healthy controls.

This suggests that they had more inflammations than healthy controls. When the parameters were analyzed separately, almost all of them showed higher concentration in the blood of depressed patients than in healthy controls (IL-1 alpha; IL-1 beta; IL-2; IL-3; IL-6; IL-7; IL-8; IL-10; IL-12; IL-18; IL-1Ra; IL-2R; IL-6R; TNF alpha; and CRP).

Only for one parameter out of 20 was a statistically significant reduction observed in depression (IL-4). For four parameters, no difference between patients and controls was observed (IL-5; IL-13; IFN gamma; and TGF beta).

What does this mean?

The results clearly show that depression and immune system function are linked and that depression is associated with inflammation. Importantly, this indicates that it might be meaningful for future studies to explore how anti-inflammatory medication could help reduce symptoms of depression.