Rare neural autoantibodies in CSF in schizophrenia spectrum

Researchers from the National Institute of Mental Health (NIH, Bethesda), the University of California, San Francisco, and Northwell Health report in Nature Communications that rare anti-neural autoantibodies can be detected in the cerebrospinal fluid (CSF) of people with schizophrenia spectrum disorders doi.org. The work was published on 3 November 2026. The team profiled CSF from 32 participants with these disorders and 32 neuropsychiatrically unaffected controls. They identified three autoantibodies, including one directed against alpha-crystallin B doi.org.

Why look for antibodies

According to the authors, schizophrenia spectrum disorders have substantial genetic liability, but their stable incidence and clinical heterogeneity leave open a contribution from non-genetic mechanisms doi.org. Autoimmune encephalitis shows that anti-neural antibodies can cause psychosis. However, the antibodies typical of encephalitis are uncommon in schizophrenia doi.org.

To search more widely, the group used multi-platform autoantigen profiling. CSF was analysed by brain tissue immunostaining, immunoprecipitation–mass spectrometry and phage display immunoprecipitation sequencing. Plasma was analysed with complementary protein microarrays. In total, three CSF methods and one plasma approach were combined doi.org.

Alpha-crystallin B antibody

The anti-alpha-crystallin B antibody preferentially recognizes phosphorylated serine-45 of the protein doi.org. It was absent from the CSF of individuals with untreated multiple sclerosis. In that disease, antibodies to unphosphorylated alpha-crystallin B are frequent, so the pattern of recognition differs between the two conditions doi.org.

The authors state that the findings do not define autoimmune psychosis as a new disease. They say the results support broader autoantibody searches in psychotic disorders doi.org. The detected autoantibodies are described as rare in schizophrenia spectrum disorders, and the 32 unaffected controls served as the reference for the CSF profiling doi.org.

NIMH and UCSF detect rare neural autoantibodies in CSF of 32 people with schizophrenia spectrum disorders

Why look for antibodies

Alpha-crystallin B antibody

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