What Causes Mental Illness? Scientists Hope Lab-Grown Mini Brains Will Help Them Find Out

Joseph Frankel

Psychiatric research is full of complex problems and the appeal of new technologies to untangle them is high. A new study in Translational Psychiatry aimed to do just that: By growing cerebral organoids, or mini brains, derived from the cells of a group of patients with schizophrenia, Michal Stachowiak’s group from the University at Buffalo claimed to be one step closer to understanding the cause of this chronic and severe mental disorder.

Schizophrenia is typically understood as an illness that starts in the brain at a very early stage of developmentStachowiak’s researchers sought to test this older hypothesis using the latest technology—growing miniature organs that mimic the real brain at the earliest stages of fetal development.

The team used skin cells from one group of adult patients diagnosed with schizophrenia as well as a group of adults who were cognitively unimpaired, and, in a process that involves bathing the cells in nutrients and spinning them through a machine that prevents gravity from flattening them, developed organoids from both groups.

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After growing the mini brains, Stachowiak ’s group compared the 'schizophrenic organoids' to the controls. The schizophrenic group, they discovered, showed architectural differences in the part of the brain known as the cortex: immature cells that would one day turn into the nerve cells known as neurons were spreading out in too many directions, with too much distance between them.

“Essentially there are hundreds if not thousands of defects in the genome [the genetic material of an organism] that lead to common diseases,” Stachowiak told Newsweek.

Stachowiak’s idea was to zero in on the changes or aberrations that this genetic pathway creates. And, he claims, problems in a genomic pathway known as INFS could lead to some of the physiological changes that are responsible for some of the symptoms of schizophrenia.  

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Stachowiak Figure

A figure from Stachowiak's paper comparing images of the organoids from the control group to the experimental group. Courtesy of University at Buffalo

“I think for the first time we have a proper experimental tool to try to see if we can either correct or prevent some of these events,” Stachowiak said.

But Madeline Lancaster, a neuroscientist at Cambridge University who was one of the first to work on organoids as a research tool nearly eight years ago, took issue with the ones used in Stachowiak’s experiments.

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Lancaster told Newsweek that trying to find some of the roots of schizophrenia using cerebral organoids was "an interesting premise,” but that the execution was lacking.

“It’s difficult with a really new field like this,” Lancaster said, admitting that her standards were “probably higher” than those of most researchers.

But, she added, the organoids that Stachowiak ’s group developed as part of this experiment were not well formed enough to make meaningful conclusions.

 The organoids Stachowiak grew, Lancaster claims, were allowed to develop randomly in a way that introduces too much heterogeneity. The small size of the study is another issue: The study looks at three control organoids and four developed from the cells of people with schizophrenia. 

Schizophrenia is a complicated diagnosis, one that is itself the subject of controversy. Organoids may be a fruitful way down the line of exploring some of these hypotheses, but the technology is still evolving. Studying the developmental factors that can contribute to schizophrenia is a live area of research, one that other neuroscientists are actively pursuing. But, as is the case with any innovation, an understanding of how best to use this new technology needs to be agreed on first.

This article was first written by Newsweek

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