Tokyo [Japan], May 31 : Autoantibodies, or immune system-produced proteins that may function against one's own body, have been linked to reports of schizophrenia. A minority of schizophrenia patients had autoantibodies that targeted neurexin 1, a "synaptic adhesion protein," according to a study published last month in Brain Behaviour and Immunity. The autoantibodies led to numerous schizophrenia-related alterations when administered to animals.
What is a synaptic protein, and why can schizophrenia be related to it? Specialised proteins known as synaptic adhesion proteins bind to form actual connections between brain cells. The cells can exchange molecules through these connections, known as synapses, to communicate. The research team from Tokyo Medical and Dental University (TMDU) opted to look into autoantibodies that target synaptic proteins in patients with schizophrenia because synapses and autoimmunity are both known to be linked to schizophrenia.
"In around 2 per cent of our patient population, we identified autoantibodies against the synaptic protein neurexin 1a, which is expressed by one cell in the synapse and binds to proteins known as neuroligins on the other cell in the synapse," says lead author of the study Hiroki Shiwaku. "Once we had identified these autoantibodies, we wanted to see if they were able to cause schizophrenia-related changes."
To do this, the researchers isolated autoantibodies from some of the patients with schizophrenia and injected them into the cerebrospinal fluid of mice, so that the autoantibodies would travel into the brain. In these mice, the autoantibodies blocked neurexin 1a and neuroligin binding and altered some related synaptic properties. The administration of these autoantibodies also resulted in fewer synapses in the brains of mice and schizophrenia-related behaviors, such as reduced social behavior toward unfamiliar mice and reduced cognitive function.
"Together, our results strongly suggest that autoantibodies against neurexin 1a can cause schizophrenia-related changes, at least in mice," explains Hiroki Shiwaku. "These autoantibodies may therefore represent a therapeutic target for a subset of patients with schizophrenia."
Schizophrenia has a wide variety of both symptoms and treatment responses, and many patients have symptoms that are resistant to currently available treatment options. Therefore, the identification of possible disease-causing autoantibodies is important for improving symptom control in patients with schizophrenia. It is hoped that the results of this investigation will allow patients with autoantibodies that target neurexin 1aall of whom were resistant to antipsychotic treatment in the present studyto better control their symptoms in the future.
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