Scientists have found that major depressive disorder (MDD) may be caused by problems in the immune system. MDD leads to low mood and loss of interest. It also greatly increases suicide risk in South Korea. But doctors still have no clear biological test to diagnose or guide treatment.
A research team at KAIST discovered that depression is not just a brain problem. Instead, the body’s immune system becomes overactive and affects how the brain works. They believe this imbalance in the “immune–neural axis” may be the key mechanism behind depression. This opens new possibilities for finding biomarkers and developing new drugs.
On November 20, KAIST announced that Professor Jinju Han’s team, together with Professor Yangsik Kim’s group from Inha University, carried out a multi-omics study. They analyzed patients’ blood, single immune cells, and brain organoids made from patient-derived stem cells. They focused on female patients with MDD who had atypical symptoms such as sleeping too much and overeating, along with psychotic symptoms like hallucinations and severe guilt.
Immune Changes And Brain Changes Occur Together
The team found genetic changes in blood immune cells and abnormal levels of proteins involved in brain function. These changes showed a clear imbalance between the immune system and the nervous system in patients with depression.
Young women often show atypical signs of MDD. These symptoms can increase the risk of developing bipolar disorder later. About 40% of all patients also do not respond to common antidepressants. Because of this, researchers have been searching for new treatments and new biological markers based on immunity and metabolism.
First Study To Combine Immune Single-Cell Analysis And Brain Organoids
The team used plasma protein analysis, single-cell analysis of white blood cells, and patient-derived brain organoids all at once. This was the first time such a combined method was used in psychiatric research.
The results showed that patients with atypical depression experienced very high levels of stress and anxiety. Two proteins needed for communication between brain cells, DCLK3 and CALY, were much higher than normal. Complement protein C5, which increases immune activity, was also elevated. This means both the brain and the immune system were overly activated and not balanced.
The researchers also found genetic changes in immune cells that make inflammation easier to trigger. This suggests the whole immune system is in an overactive state. Such strong immune activity may play a key role in the development of depression.
Brain organoids grown from patient cells showed slower growth and abnormal neural development. This supports the idea that immune problems can affect brain function.
Immune–Neural Axis Imbalance May Be The Key Cause
By combining clinical data with single-cell, protein, and organoid studies, the team showed that an imbalance in the immune–neural axis is likely a core mechanism of MDD, especially in patients with atypical and psychotic symptoms. This mechanism may help guide future diagnosis and treatment strategies.
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