Researchers have grown tiny brain organoids in the lab, about the size of a pea, opening up new possibilities for studying how neurons behave in conditions like schizophrenia and bipolar disorder. These mental illnesses affect millions of people worldwide, but diagnosing them remains challenging due to a limited understanding of the underlying molecular mechanisms.

New Approaches to Diagnosing Mental Disorders

The findings could help doctors reduce diagnostic and treatment errors for mental illnesses in the future. Currently, many psychiatric diagnoses are based on clinical experience, and medication selection often relies on trial and error. The study, published in the journal APL Bioengineering, offers more precise tools for diagnosis.

Why Are Schizophrenia and Bipolar Disorder Hard to Detect?

According to biomedical engineer Anni Kathuria from Johns Hopkins University, who led the study, unlike some other diseases such as Parkinson’s, schizophrenia and bipolar disorder lack specific biomarkers or enzymes that could guide diagnosis and treatment. Kathuria notes that in the future, brain organoids could not only confirm diagnoses but also serve as a platform for testing medications to determine the most effective dosages for each patient.

How Brain Organoids Were Created and Studied

Kathuria’s team developed simplified models of the human brain—organoids—using blood and skin cells from patients with schizophrenia, bipolar disorder, and healthy individuals. These cells were reprogrammed into stem cells capable of developing into tissue resembling brain matter.

Using machine learning methods, the scientists analyzed the electrical activity of cells inside the mini-brains. In the human brain, neurons communicate through brief electrical signals, and the researchers focused on identifying patterns linked to healthy and pathological brain function.

Electrical Biomarkers of Mental Illness

The researchers discovered that certain features of the organoids’ electrical activity could serve as biomarkers for schizophrenia and bipolar disorder. Using only these signals, they were able to correctly identify the origin of the organoids (healthy or affected patient) in 83% of cases. After gentle electrical stimulation of the tissue, accuracy increased to 92%.

The identified patterns were complex and specific: neurons from patients with mental disorders showed unusual bursts and changes in several electrical parameters, creating a unique “signature” for each condition.

Molecular Differences and the Future of Personalized Therapy

Kathuria points out that at the molecular level, organoids from healthy individuals, schizophrenia patients, and those with bipolar disorder can be distinguished by their electrophysiological characteristics. The researchers track the electrical signals produced by neurons during development and compare them across different patient groups.

Using Microchips to Map Brain Activity

To better understand how neural networks form, the organoids were placed on microchips with multi-electrode arrays, allowing the collection of data similar to a miniature electroencephalogram (EEG). Once fully developed, the organoids reached about three millimeters in diameter and contained several types of nerve cells typical of the prefrontal cortex—the brain region responsible for higher cognitive functions. The mini-brains also produced myelin, which helps transmit electrical signals efficiently.

Personalized Treatment for Mental Disorders

The study used samples from just 12 patients, but Kathuria believes the results point to promising clinical applications. In the future, organoids could become a platform for testing psychiatric drugs before they are prescribed to patients.

Currently, the team is collaborating with neurosurgeons, psychiatrists, and neurobiologists at the Johns Hopkins School of Medicine, collecting additional blood samples from psychiatric patients to study how different drug concentrations affect organoid activity. Even with a limited number of samples, the researchers hope to identify dosages that help restore healthier neural patterns.

Kathuria notes that today, finding the right medication often takes six to seven months, as doctors must rely on trial and error. For example, clozapine is the most commonly used drug for schizophrenia, but about 40% of patients do not respond to it. Using organoids could significantly speed up the search for effective treatments, allowing doctors to select the right medication more quickly and accurately.