<(From Left) Professor Jinju Han, Dr. Gyuhyun Baek, Dr. Dayeon Kim, Dr. Geurim Son, Dr. Hyunsu Do>
Bipolar disorder, also known as 'manic-depressive illness,' a brain disorder known to have afflicted the famous painter Vincent van Gogh, is characterized by recurrent episodes of mania and depression. This disease affects about 1-2% of the world's population, and the risk of suicide is 10 to 30 times higher than in the general population. However, because each patient's response to lithium, the main treatment, varies greatly, there is an urgent need to develop personalized treatments. In response, a research team at KAIST has identified the differences in lithium responsiveness and presented the new possibility of developing personalized treatments and a drug discovery platform based on this finding.
On September 10th, the research team led by Professor Jinju Han from the KAIST Graduate School of Medical Science and Engineering announced they were the first to identify metabolic differences in astrocytes based on lithium responsiveness, thereby suggesting the potential for personalized treatment development for bipolar disorder.
Astrocytes are star-shaped cells in the brain that act as 'helpers to neurons,' providing them with nutrients and maintaining the brain's environment.
Breaking away from the existing neuron-centric research paradigm, Professor Jinju Han's team focused on astrocytes, which make up half of the brain's cells, and discovered that they play a key role in regulating the metabolism of bipolar disorder.
The research team differentiated induced pluripotent stem cells (iPSCs) from patients' cells into astrocytes (a process in which stem cells grow and specialize into cells with specific functions) and observed them. As a result, it was confirmed that the cells' energy metabolism changed significantly depending on whether they responded to lithium.
In cases of no lithium response, distinct metabolic abnormalities were observed, including an excessive accumulation of lipid droplets (tiny fat storage depots) inside the cells, decreased mitochondrial function (the cell's power plant), an over-activation of the glucose breakdown process, and excessive lactate secretion.
Specifically, in the astrocytes of lithium-responsive patients, lipid droplets decreased upon lithium treatment, but there was no improvement in non-responsive patients. Furthermore, significant differences were found in the metabolites produced by astrocytes depending on the patient type. This suggests that the cell's energy factory does not function properly depending on the lithium response, and alternative pathways are overused, leading to a buildup of byproducts.
This finding is particularly significant as it proves that astrocytes play a key role in regulating energy metabolism in bipolar disorder, explaining the differences in lithium responsiveness and paving the way for personalized treatment strategies for each patient.
Professor Jinju Han stated, "The development of new treatments targeting astrocytes is now possible, which could provide better treatment strategies for patients who do not respond to existing medications."
This research was published online on August 22 in Molecular Psychiatry, a leading international journal in the field of neuropsychiatric disorders.
※ Paper Title: Differential effects of lithium on metabolic dysfunctions in astrocytes derived from bipolar disorder patients DOI: https://doi.org/10.1038/s41380-025-03176-w
※ Author Information: Gyuhyun Baek, Dayeon Kim, Geurim Son, Hyunsu Do (KAIST, co-first authors) and Jinju Han (KAIST, corresponding author).
This research was supported by the National Research Foundation of Korea and the Korea Environmental Industry and Technology Institute, among others.
