Neural autoantibodies in the cerebrospinal fluid of individuals with schizophrenia spectrum disorders

Abstract

Schizophrenia spectrum disorders have substantial genetic liability, but their stable incidence and clinical heterogeneity leave open contributions from non-genetic mechanisms. Though autoimmune encephalitis demonstrates that anti-neural antibodies can cause psychosis, encephalitis antibodies are uncommon in schizophrenia. Here we show that multi-platform autoantigen profiling of cerebrospinal fluid and plasma detects rare, anti-neural autoantibodies in schizophrenia spectrum disorders. By antibody profiling the cerebrospinal fluid of 32 schizophrenia spectrum participants and 32 neuropsychiatrically unaffected controls by brain tissue immunostaining, immunoprecipitation–mass spectrometry, phage display immunoprecipitation sequencing, and plasma by complementary protein microarrays, we identify three autoantibodies, including to alpha-crystallin B. The anti-alpha-crystallin B antibody preferentially recognizes phosphorylated serine-45 and is absent from the cerebrospinal fluid of individuals with untreated multiple sclerosis, a disease with frequent antibodies to unphosphorylated alpha-crystallin B. These findings do not define autoimmune psychosis as a new disease but support broader autoantibody searches in psychotic disorders.

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BibTeX RIS

BibTeX

@article{pandit2026neural,
  title = {{Neural autoantibodies in the cerebrospinal fluid of individuals with schizophrenia spectrum disorders}},
  author = {P. R. Pandit and S. L. Listwak and T. T. Ngo and M. T. Salem and T. J. Esparza and P. P. Khil and R. Dandekar and B. D. Alvarenga and G. C. Mooneyham and K. L. Hamilton and J. L. DeRisi and A. Nath and R. Gomez and B. A. C. Cree and S. L. Hauser and K. A. Fiore and T. Lencz and J. A. Gallego and M. R. Wilson and S. J. Pleasure and C. M. Bartley},
  journal = {Nature Communications},
  year = {2026},
  month = nov,
  doi = {10.1038/s41467-026-78783-4},
  url = {https://www.nature.com/articles/s41467-026-78783-4},
  note = {CC BY 4.0},
}

RIS

TY  - JOUR
TI  - Neural autoantibodies in the cerebrospinal fluid of individuals with schizophrenia spectrum disorders
AU  - P. R. Pandit
AU  - S. L. Listwak
AU  - T. T. Ngo
AU  - M. T. Salem
AU  - T. J. Esparza
AU  - P. P. Khil
AU  - R. Dandekar
AU  - B. D. Alvarenga
AU  - G. C. Mooneyham
AU  - K. L. Hamilton
AU  - J. L. DeRisi
AU  - A. Nath
AU  - R. Gomez
AU  - B. A. C. Cree
AU  - S. L. Hauser
AU  - K. A. Fiore
AU  - T. Lencz
AU  - J. A. Gallego
AU  - M. R. Wilson
AU  - S. J. Pleasure
AU  - C. M. Bartley
PY  - 2026
DA  - 2026/11/03
JO  - Nature Communications
DO  - 10.1038/s41467-026-78783-4
UR  - https://www.nature.com/articles/s41467-026-78783-4
AB  - Schizophrenia spectrum disorders have substantial genetic liability, but their stable incidence and clinical heterogeneity leave open contributions from non-genetic mechanisms. Though autoimmune encephalitis demonstrates that anti-neural antibodies can cause psychosis, encephalitis antibodies are uncommon in schizophrenia. Here we show that multi-platform autoantigen profiling of cerebrospinal fluid and plasma detects rare, anti-neural autoantibodies in schizophrenia spectrum disorders. By antibody profiling the cerebrospinal fluid of 32 schizophrenia spectrum participants and 32 neuropsychiatrically unaffected controls by brain tissue immunostaining, immunoprecipitation–mass spectrometry, phage display immunoprecipitation sequencing, and plasma by complementary protein microarrays, we identify three autoantibodies, including to alpha-crystallin B. The anti-alpha-crystallin B antibody preferentially recognizes phosphorylated serine-45 and is absent from the cerebrospinal fluid of individuals with untreated multiple sclerosis, a disease with frequent antibodies to unphosphorylated alpha-crystallin B. These findings do not define autoimmune psychosis as a new disease but support broader autoantibody searches in psychotic disorders.
SN  - 2041-1723
ER  -

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