Body versus brain: New evidence for an autoimmune cause of schizophrenia

Schizophrenia is a mental illness that affects people's actions, thoughts, and perceptions of reality. Because there are so many distinct causes and symptoms, it's frequently difficult to cure. Researchers from Tokyo Medical and Dental University (TMDU) discovered an autoantibody — a protein produced by the immune system to attach to a specific substance from the individual's own body rather than a foreign substance like a virus or bacteria — in some patients with schizophrenia, according to a study published last month in Cell Reports Medicine. When scientists administered this autoantibody into mice, they discovered that it triggered schizophrenia-like behaviour and brain abnormalities.

The study team had a specific protein in mind while researching potential autoantibodies that may cause schizophrenia. Previous study has shown that NCAM1, a protein that helps brain cells communicate with one another via specialized connections known as synapses, may have a role in the development of schizophrenia.

"We decided to look for autoantibodies against NCAM1 in around 200 healthy controls and 200 patients with schizophrenia," says Hiroki Shiwaku, the study's main author. "We only found these autoantibodies in 12 patients, suggesting that they may be associated with the disorder in just a small subset of schizophrenia cases." 

The researchers didn't stop there; they wanted to see if the autoantibodies might induce any of the alterations seen in schizophrenia patients, so they isolated autoantibodies from some of the patients and injected them into mice's brains.

"The results were impressive," says senior author Hidehiko Takahashi. "Even though the mice only had these autoantibodies in their brains for a short time, they had changes in their behavior and synapses that were similar to what is seen in humans with schizophrenia." 

Mice with patient autoantibodies displayed cognitive impairment and alterations in their startle reflex modulation, both of which have been observed in earlier animal models of schizophrenia. They also exhibited less synapses and dendritic spines, which are critical components for brain cell interactions that are also damaged in schizophrenia.

Given that schizophrenia can manifest itself in a variety of ways and is frequently resistant to therapy, the findings of this study are encouraging. If autoantibodies to NCAM1 are shown to be the cause of schizophrenia in certain people, this will lead to significant advancements in their diagnosis and treatment.