Is Depression a Mental Illness? ... Abnormal Immune Responses in the Body Also Play a Role

A new study has found that immune system abnormalities are a key mechanism underlying major depressive disorder (hereafter referred to as depression). The research suggests that immune dysfunction can affect brain function, leading to an imbalance in the "immune-neural axis" that may trigger depression. This implies that the causes of depression should not be limited to emotional (psychological) or brain-related factors alone, but should also encompass abnormal immune responses.

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KAIST announced on November 20 that a research team led by Professor Jinju Han at the Graduate School of Medical Science and Engineering, in collaboration with Professor Yangsik Kim (PhD, KAIST Graduate School of Medical Science and Engineering) at Inha University College of Medicine, produced these research results.

The joint research team analyzed multi-omics data by combining blood and single-cell analyses with brain organoids (mini-brains) derived from patients. The subjects were women with depression who exhibited "atypical features" such as hypersomnia and excessive eating-symptoms opposite to typical depression-and "psychotic symptoms" such as impaired reality testing, auditory hallucinations, excessive guilt, or self-blame.

First, when examining changes in immune cell genes and neuro-related proteins in the blood simultaneously, the researchers found that the balance of immune-neural interactions was disrupted in patients with depression.

This result adds weight to the need for identifying immune- and metabolism-based biomarkers and developing new treatment strategies, moving beyond the traditional drug-centered approach.

Depression, especially in young women, often manifests with atypical symptoms, which increases the risk of later being diagnosed with bipolar disorder. Additionally, about 40% of patients are classified as having treatment-resistant depression, meaning they do not respond to multiple antidepressants.

(From left) KAIST PhD candidate Insook Ahn, Professor Jinju Han, (From top left) Professor Yangsik Kim of Inha University College of Medicine, PhD candidate Soyeon Jang (psychiatrist). Provided by KAIST

The joint research team also presented the world’s first precision medicine approach that integrates plasma proteomics, single-cell transcriptomics of leukocytes, and analysis of brain organoids created from patient blood-derived induced pluripotent stem cells (iPSCs).

Through this approach, they confirmed that patients with atypical depression exhibit high levels of stress, anxiety, and depression, and that proteins critical for signaling between brain cells (DCLK3, CALY) increased sharply beyond normal levels. They also observed an increase in "complement protein C5," which strongly activates the body’s immune response.

This indicates that both "brain function" and "immune function" are excessively activated and out of balance in the bodies of patients with depression.

The joint research team emphasizes that the series of findings from this study provide evidence that depression is not simply a mood disorder, but is linked to biological changes occurring throughout the entire body.

This research is significant in that it integrated clinical data, single-cell omics, proteomics, and brain organoids to identify that the core mechanism of major depression with atypical and psychotic symptoms is an "imbalance in the immune-neural axis."

Professor Han stated, "Through this study, the joint research team has proposed a new precision medicine model for psychiatric disorder research," adding, "We hope this will lead to active identification of biomarkers and the development of new drugs."

This research was supported by the National Research Foundation of Korea and the Korea Health Industry Development Institute, among others. The results (paper) were recently published online in the international scientific journal 'Advanced Science.'

This content was produced with the assistance of AI translation services.