Annie Kathuria brain organoid made in the doctoral lab of Kathuria Annie at Johns Hopkins University's Department of Biomedical Engineering shows neurons marked in various colors sending signals and forming a complex neural network. /Courtesy of Annie Kathuria

U.S. researchers have, for the first time, revealed how neurons malfunction in the brains of people with schizophrenia and bipolar disorder (manic-depressive illness) using lab-grown brain organoids (mini organs). The study is expected to offer a new clue for precise diagnosis of mental illness and the development of personalized treatments.

A research team led by Annie Kathuria, a professor in the Department of Biomedical Engineering at Johns Hopkins University, said in the international journal APL Bioengineering on the 22nd (local time) that they confirmed that neurons in brain organoids from patients with schizophrenia and bipolar disorder show signaling patterns that are clearly different from those in the brains of healthy people.

Schizophrenia and bipolar disorder are mental illnesses experienced by millions worldwide, but diagnosis is difficult because no clear cause has been identified to date. It often takes patients an average of six to seven months to find a medication that works.

The researchers reprogrammed blood and skin cells from patients with mental illness and from healthy people into stem cells and used them to create brain organoids. They then analyzed neuronal electrical signaling patterns with an artificial intelligence (AI) algorithm. In the brain, neurons communicate by exchanging tiny electrical signals, and the team measured several indicators such as the frequency, interval, and intensity of these signals.

As a result, electrical signals from neurons appeared regular in organoids from healthy people, whereas in organoids from patients, the timing and intervals of neuronal firing were irregular and intricately intermingled. When this pattern was analyzed by AI, it distinguished healthy organoids from patient organoids with 83% accuracy.

Kathuria said, "Schizophrenia and bipolar disorder are not diseases that can be diagnosed immediately because a specific part of the brain is damaged or an enzyme is missing, like Parkinson's disease," adding, "But using organoids, we can tell what disease a patient has and test which drugs work best at what concentrations."

The team is currently recruiting actual patient blood samples in collaboration with researchers in neurosurgery, psychiatry, and neuroscience at the Johns Hopkins University School of Medicine and is studying how various drug concentrations affect the electrical activity of organoids.

References

APL Bioengineering (2025), DOI: www.doi.org/10.1063/5.0250559

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