Signature for schizophrenia, bipolar disorder suggests changes in the cellular makeup of the brain

Dr. Paul Pavlidis.

Pictured: Dr. Paul Pavlidis. Image credit: Michael Smith Laboratories, UBC.

Scientists have long studied brain tissue in a search for the functional changes to the brain that accompany psychiatric disease. But the complexity of the brain presents challenges: the brain is made up of dozens of different types of cells. If researchers could inspect each cell type individually, they could gain greater insight into how the brain changes with psychiatric disorders including schizophrenia and bipolar disorder. 

With these challenges in mind, Dr. Paul Pavlidis and his team are taking a novel approach to cellular data analysis. Last year, the team launched NeuroExpresso, an online resource for researchers looking to parse the genetic details of different brain cell types. Using NeuroExpresso and some recently-developed bioinformatics methods, Dr. Pavlidis and colleagues are beginning to look at genomic data to identify a signature for schizophrenia and bipolar disorder at the cellular level. 

“By looking at genomic data in a different way, we’re able to see specific patterns associated with different types of cells, despite them being all mixed together,” said Dr. Pavlidis. “We’ve detected a signature that is consistent with the effects of schizophrenia on two different cell types in the brain.”

The team evaluated 15 publicly available datasets on schizophrenia and bipolar disorder, in which gene activity had been measured in a part of the brain thought to be key to the disorders. By using the new methods, the team were able to assess the relative amounts of different cell types in the tissue.

Their findings were published this month in the journal Biological Psychiatry.

“Despite these data sets being collected by many different laboratories, we observed a consistent increase in the expression profiles of astrocytes (an important type of non-neuronal cell), and a decrease in a particular class of inhibitory neurons,” said Dr. Pavlidis. “This raises the possibility that schizophrenia and bipolar disorder are characterized in part by changes in the numbers of these two cell types in an area of the brain long thought to be critical to cognition and behavior.”

For Dr. Pavlidis, the scope and number of individual cell types in the brain elevates the importance of identifying cell-type specific changes. “It’s not a new idea that there might be changes in cell makeup of the brain in schizophrenia, but this is the first time such a consistent and clear signal has been found in such a wide range of data sets.” At this stage, the team is not sure whether the cellular changes are a cause or a symptom of psychiatric illness, but the team is excited to have an informed, testable hypothesis based on consistent signals in the data sets.

“Relating these findings to specific changes in brain function is still a long way off, but clearly gaining an understanding how psychiatric disease affects different types of cells in the brain is going to be essential,” said Dr. Pavlidis.

For more information on NeuroExpresso, visit neuroexpresso.org