New Study Finds Links Between Schizophrenia and Autoimmunity

Patients with schizophrenia are symptomatically and genetically heterogeneous, and it is assumed that there are various underlying pathological mechanisms. However, there are no biomarkers for these heterogeneous subgroups, and elucidation of pathological mechanisms underlying treatment resistance in patients and/or symptoms is insufficient.

Genetic analysis has revealed risk genes related to the synapse, chromatin modification, and the immune system, especially some mutations in the major histocompatibility complex region carry the highest risk of schizophrenia, and this complex plays a role in autoimmunity. 

In a recently published study, researchers from Tokyo Medical and Dental University have identified an autoantibody, a protein that is produced by the immune system to attach to a specific substance from the individual’s own body, in some patients with schizophrenia. The results appear in the journal Cell Reports Medicine. 

Autoantibodies Against NCAM1

During the study, the team identified that some schizophrenic patients had anti-NCAM1 autoantibodies.  NCAM1 is a neural cell adhesion molecule that supports synaptic connections, and also binds to glial-cell-line-derived neurotrophic factor (GDNF) and contributes to synapse formation. 

The researchers looked for these autoantibodies in around 200 healthy controls and 200 patients with schizophrenia and found them in only 12 patients, suggesting that they may be associated with the disorders in just some patients. 

The team then used a mice model to administer immunoglobulin G (IgG) from patients with schizophrenia and found that anti-NCAM1 autoantibodies inhibit spine and synapse formation in the frontal cortex and induce schizophrenia-related behavior. 

The findings could lead to important improvements in their diagnosis and treatment, at least in some patients. 

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Source:

Hiroki Shiwaku, et al. Autoantibodies against NCAM1 from patients with schizophrenia cause schizophrenia-related behavior and changes in synapses in mice. 2022. Cell Reports Medicine. DOI:https://doi.org/10.1016/j.xcrm.2022.100597. 

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