Study Details New Information About the Biology of Schizophrenia

Researchers have identified a specific gene and biological process that may increase risk of developing the disorder.


Harvard Medical School photo by Alex Lau

Psychiatric disorders are notoriously poorly understood. Despite the fact that 13.6 million Americans live with a serious mental illness, concrete information about the biology of psychiatric disorders has been limited—until now.

A team of researchers from Harvard Medical School (HMS), Boston Children’s Hospital, and the Broad Institute just published a study about the biologic and genetic roots of schizophrenia. They examined the genes and biological processes that may predispose an individual to developing the disorder, arguing that the disease’s formation is likely linked to excess synaptic pruning, the process through which children’s brains get rid of unnecessary neurological connections as they age.

The team also pinpointed the specific genes that may be most closely linked with schizophrenia. They began by looking at the MHC, a region of the human genome known to be related to schizophrenia, in 65,000 people. They found that people with schizophrenia are more likely to have a variant of the C4 gene—which the MHC produces—called C4-A. “The evidence strongly suggested that too much C4-A leads to inappropriate pruning during this critical phase of development,” researcher Beth Stevens told the New York Times.

Having overactive C4-A alone would not be enough to cause schizophrenia, the researchers say, but it could contribute to excess synaptic pruning, and the schizophrenia that potentially results. Given that schizophrenia often manifests during adolescence, around the same time as synaptic pruning, the connection seems significant.

It’s important to note that the findings do not immediately translate to new treatments for schizophrenia. A deeper understanding of the disorder may, however, help scientists advance research about the condition. In a statement, senior author Steven McCarroll spoke about the implications of the discovery:

“Since schizophrenia was first described over a century ago, its underlying biology has been a black box, in part because it has been virtually impossible to model the disorder in cells or animals. Understanding these genetic effects on risk is a way of prying open that black box, peering inside and starting to see actual biological mechanisms.”