Researchers have utilized advanced technology to gain new insights into the neurodevelopmental origins of schizophrenia. Two recent studies published in Biological Psychiatry shed light on the disorder by exploring brain organoids and a risk gene associated with schizophrenia.
In the first study, researchers from Oslo University Hospital collected skin cells from 14 schizophrenia patients and 14 healthy controls. They manipulated these cells to grow brain-like cortical spheroids, or brain organoids. Comparing the organoids from patients and controls, the researchers found differences in the expression of thousands of genes, with those associated with neuronal axons standing out. This suggests that persistent axonal dysregulation is an early contributor to schizophrenia.
The researchers also studied the maturation of the brain organoids at various time points, revealing that the axonal disruptions persisted throughout development. These findings provide new insights into the molecular basis of schizophrenia during early brain development.
In the second study, led by researchers from Harvard Medical School, the focus was on a schizophrenia risk gene called CYFIP1. This gene is situated in a schizophrenia risk locus and has been associated with synaptic function as well as increased risk for neurodevelopmental disorders like schizophrenia and autism. The researchers discovered that CYFIP1 is highly expressed in microglia, the brain’s immune cells.
The team used CRISPR technology to remove functional CYFIP1 from microglia-like cells derived from induced pluripotent stem cells (iPSCs). They observed a decrease in the phagocytosis of synaptic vesicles, which is a model of synaptic pruning. Disturbances in synaptic pruning have been linked to problems in brain development.
These studies highlight the importance of non-neuronal cells, such as microglia, in understanding and potentially treating neuropsychiatric disorders like schizophrenia. Further research into the genetic and molecular mechanisms that underlie early brain development may contribute to the development of novel treatments for the disorder.