Brigham and Women’s Researchers Are Building Stem Cell Models of Mental Illness

As part of a new study, Brigham and Women’s Hospital researchers used stem cells to build models of the genetic mutations behind mental illnesses like schizophrenia, bipolar disorder, depression, and autism, an advance that could help scientists better understand the complex inner workings of mental illness.

“There’s a general consensus in the field that there’s something going on in neurodevelopment [to cause mental illness],” says Tracy Young-Pearse, corresponding author of the paper that accompanied the study. “The problem is, of course, that that’s a really tough thing to study, because obviously we can’t do experiments on developing human brains. We started using human stem cells as a way to study brain development in a dish.”

To be exact, the researchers took stem cells from a healthy person and manipulated a particular gene, DISC1, that is closely linked to mental illness to see how the brain develops when the gene is disrupted. They then programmed the stem cells to mimic the cells that make up the brain’s cerebral cortex, allowing for further study of the differences between a brain with mental illness and a typical adult brain.

“It’s just building knowledge to better understand what the problem is in the first place,” Young-Pearse says. “Here, we can look at human neurons that actually have a genetic predisposition to the disease that you’re interested in treating. It may give us a better chance at finding something that’s effective.”

In addition, the stem cell models may help researchers better understand why four seemingly disparate conditions—bipolar disorder, schizophrenia, autism, and depression—share so much genetically. “They’re similar disorders in that a similar process is affected, but it’s affected in opposite ways,” Young-Pearse explains. In other words, having too much DISC1 could cause one disease, while not having enough could catalyze another.

While the stem-cell based models are just the beginning, Young-Pearse says any increase in mental illness knowledge could have a critical impact on treatment. “If we can understand how it got to the point where it has these altered communications between different types of neurons,” she says, “we might be able then, in a smarter way, say, ‘These are the pathways we should target in the adult brain to fix that problem.'”