Autoimmunity and Schizophrenia Might Be Linked

In a recent study, Japanese researchers identified autoantibodies that target a ‘synaptic adhesion protein’, neurexin 1α, in a subset of patients with schizophrenia. 

Synaptic adhesion proteins are specialized proteins that bind to create physical connections between brain cells. These connections, called synapses, allow the cells to communicate by passing molecules back and forth. Both synapses and autoimmunity are known to be associated with schizophrenia, so the research team decided to investigate autoantibodies that target synaptic proteins in patients with schizophrenia.

“In around 2% of our patient population, we identified autoantibodies against the synaptic protein neurexin 1α, 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.”

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. The autoantibodies blocked neurexin 1α 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 1α 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.”

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Sources:

Hiroki Shiwaku, Shingo Katayama, Mengxuan Gao, Kanoh Kondo, Yuri Nakano, Yukiko Motokawa, Saori Toyoda, Fuyuko Yoshida, Hiroaki Hori, Tetsuo Kubota, Kinya Ishikawa, Hiroshi Kunugi, Yuji Ikegaya, Hitoshi Okazawa, Hidehiko Takahashi. Analyzing schizophrenia-related phenotypes in mice caused by autoantibodies against NRXN1α in schizophrenia. Brain, Behavior, and Immunity, 2023; 111: 32 DOI: 10.1016/j.bbi.2023.03.028

Tokyo Medical and Dental University. “Further link identified between autoimmunity and schizophrenia.” ScienceDaily. ScienceDaily, 31 May 2023. <www.sciencedaily.com/releases/2023/05/230531150109.htm>.

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