Korea Advanced Institute of Science and Technology (KAIST) said on the 10th that a research team led by Graduate School of Medical Science and Engineering Professor Han Jin-ju found that the metabolic mode of astrocytes in the brain changes depending on response to treatment for bipolar disorder.
Bipolar disorder is a brain disease in which manic episodes of elevated mood and severe depression recur, affecting 12% of the global population and carrying a risk of extreme choices that is 10 to 30 times higher than in the general population. However, lithium, a standard treatment, varies in effectiveness from patient to patient, limiting individualized care.
Astrocytes, another name for astroglia, are star-shaped non-neuronal cells that support neurons in the brain and regulate neural circuits.
Han's team focused on astrocytes, which make up half of the brain. Astrocytes are star-shaped cells that supply nutrients to neurons and act as "neuron helpers" that maintain the brain environment. Unlike previous neuron-centered research, the team found that astrocytes play a key role in regulating energy metabolism in patients with bipolar disorder. The findings were published last month in the international journal Molecular Psychiatry.
The team grew patient-derived stem cells into astrocytes and observed lithium responsiveness. As a result, cells that did not respond to lithium accumulated lipid droplets, showed reduced mitochondrial function that generates energy, exhibited excessively active glucose breakdown, and accumulated large amounts of lactate, indicating metabolic problems. By contrast, in astrocytes from lithium-responsive patients, lipid droplets decreased and energy metabolism normalized when treated with lithium.
The metabolic products produced by astrocytes also differed by patient type. This shows that, depending on lithium responsiveness, the cells' energy factories do not function properly, causing alternative pathways to be overused and byproducts to accumulate.
Han Jin-ju said, "This study makes it possible to develop new therapeutics targeting astrocytes," adding, "It could also provide personalized treatment strategies for patients who have not responded to existing medications."
References
Molecular Psychiatry (2025), DOI: https://doi.org/10.1038/s41380-025-03176-w