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Symptoms of schizophrenia typically don’t appear until young adulthood, but new research reveals that the disease likely starts well before birth.

Scientists at the University at Buffalo have found striking indications that the disease originates in early fetal development, through malformations in the cerebral cortex. That’s the largest part of the brain, responsible for such critical functions as memory, cognition and language.

In the brains of those with schizophrenia, says lead author Michal K. Stachowiak, a professor in the Department of Pathology and Anatomical Sciences, specific neurons that connect different regions of the cortex become misdirected, “like an improperly wired computer.”

The finding offers new insight into this devastating disease and the potential for new treatment possibilities in utero.

The research builds on previous work by Stachowiak and his colleagues showing that although hundreds of different genetic mutations may be responsible for schizophrenia, they all converge in a single faulty genomic pathway, called INFS. But when and how dysregulation of that pathway occurs, and how it affects brain development, was a mystery.

To solve it, they used “mini-brain” technology to replicate the stages of brain formation that take place in the womb.

Skin cells from patients with schizophrenia, along with controls, were reprogrammed in the lab into a type of stem cell. These eventually grew into miniature structures resembling the developing human brain.

The researchers discovered critical malformations in the cortex of the mini-brains formed from the cells of the patients with schizophrenia. Certain cells—those destined to later become neurons—were abnormally distributed. And while maturing neurons were plentiful outside of the cortex, they were rare in the cortex.

“The next step is to investigate how to target the INFS pathway using drugs or even dietary supplements that could prevent the dysregulation from taking place,” says Stachowiak, noting that this type of supplementation has already proven effective with other disorders, such as spina bifida.