KAIST study links immune system dysregulation to depression symptoms

Depression isn't just about the mind, but can come from an imbalance in the body's immune system that leads to a complicated reaction from the brain and nervous system, according to a team of researchers at KAIST.

A diagram of from the "Exploration of Novel Biomarkers Through a Precision Medicine Approach Using Multi-Omics and Brain Organoids in Patients With Atypical Depression and Psychotic Symptoms" study by a team of researchers at KAIST [KAIST]

Depression isn't just about the mind, but can come from an imbalance in the body's immune system that leads to a complicated reaction from the brain and nervous system, according to a team of researchers at KAIST.

The team, led by Professor Han Jin-ju at the Graduate School of Medical Science and Engineering at KAIST, collaborated with Professor Kim Yang-sik from Inha University Hospital's Department of Psychiatry to release their study, "Exploration of Novel Biomarkers Through a Precision Medicine Approach Using Multi-Omics and Brain Organoids in Patients With Atypical Depression and Psychotic Symptoms," in Advanced Science, an interdisciplinary, open-access peer-reviewed journal.

The team used brain organoids — organic tissues made to resemble actual human organs — along with clinical data, white blood cell single-cell RNA sequencing and plasma proteomics to identify the biomarkers in female patients with major depressive disorder (MDD) with atypical features accompanied by psychotic symptoms. Symptoms include excessive sleep, excessive eating and mood swings and patients are more likely to be diagnosed with schizophrenia.

According to the research, patients with MDD displayed increased inflammation and immune dysregulation compared to the control group, as well as reduced growth and distinct gene expression patterns. The models also showed higher levels of Doublecortin-Like Kinase 3 and Calcyon, proteins used in synaptic formation, and immune-related proteins such as Complement Component 5 — meaning that patients with MDD were showing signs of excessive brain activity and excessive immune reactions.

Researchers of the "Exploration of Novel Biomarkers Through a Precision Medicine Approach Using Multi-Omics and Brain Organoids in Patients With Atypical Depression and Psychotic Symptoms" study, from left: Ahn In-sook, Han Jin-ju, Kim Yang-sik and Chang So-yeon [KAIST]

Further research also revealed that the patients' immune cells were genetically altered to react more easily and more strongly to inflammation within the body, which can influence the onset of depression within a patient.

The research proves that depression is not just a "sad feeling" but a physical reaction from the mechanics of the body, according to KAIST.

"We have proposed a new model of precision medicine in the field of psychotic disease research," said Prof. Han. "We hope to see new biomarkers and medicine developed based on this research."

BY YOON SO-YEON [yoon.soyeon@joongang.co.kr]