Schizophrenia, which affects how people interact with reality, is difficult to treat because it has many possible causes. In a study published in Cell Reports Medicine, Japanese researchers have identified an autoantibody – an antibody which attacks the body’s own tissues – in some patients with schizophrenia.
Notably, they also found that this autoantibody caused schizophrenia-like behaviours and changes in the brain when they injected it into mice.
When considering possible autoantibodies that might cause schizophrenia, researchers from Tokyo Medical and Dental University (TMDU) had a specific protein in mind. Previous research has suggested that neural cell adhesion molecule (NCAM1), which helps facilitate synaptic connections, 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,” explained lead author of the study Hiroki Shiwaku. “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 research went on to find out whether these autoantibodies could cause any changes that commonly occur in schizophrenia, so they purified autoantibodies from some of the patients and injected them into the brains of mice.
“The results were impressive,” said the study’s senior author, Hidehiko Takahashi. “Even though the mice only had these autoantibodies in their brains for a short time, they had changes in their behaviour and synapses that were similar to what is seen in humans with schizophrenia.”
The mice given the patient autoantibodies had cognitive impairment and changes in their regulation of the startle reflex, which are both seen in other animal models of schizophrenia. They also had fewer synapses and dendritic spines, which are structures that are important for the connections between brain cells, and are also affected in schizophrenia.
The study findings hold promise for the diagnosis and treatment of schizophrenia can present very differently among patients and is often resistant to treatment. If schizophrenia is indeed caused by autoantibodies against NCAM1 in some patients, this will lead to important improvements in their diagnosis and treatment.
