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.
Authors
- Avindra Nath (ORCID: https://orcid.org/0000-0003-0927-5855)
- Samuel J. Pleasure (ORCID: https://orcid.org/0000-0001-8599-1613)
- Todd Lencz (ORCID: https://orcid.org/0000-0001-8586-338X)
- GenaLynne C. Mooneyham (ORCID: https://orcid.org/0000-0001-5808-0734)
- Bruce Cree (ORCID: https://orcid.org/0000-0001-7689-2533)
- Pavel P. Khil (ORCID: https://orcid.org/0000-0002-4903-8777)
- Joseph L. DeRisi (ORCID: https://orcid.org/0000-0002-4611-9205)
- Madeleine Salem (ORCID: https://orcid.org/0009-0004-6259-3902)
- Christopher M. Bartley (ORCID: https://orcid.org/0000-0002-1391-4130)
- Kelly L. Hamilton (ORCID: https://orcid.org/0000-0002-3502-7479)
- Michael Wilson (ORCID: https://orcid.org/0000-0001-8983-0067)
- Stephen L. Hauser (ORCID: https://orcid.org/0000-0002-4932-4001)
- R. Dandekar
- R. Gomez
- S. L. Listwak
- B. D. Alvarenga
- J. A. Gallego
- K. A. Fiore
- T. T. Ngo
- P. R. Pandit
- T. J. Esparza
Institutions
- National Institutes of Health (US)
- Northwell Health (US)
- Feinstein Institute for Medical Research (US)
- Hofstra University (US)
- University of California, San Francisco (US)
- Chan Zuckerberg Biohub San Francisco (US)
- Donald & Barbara Zucker School of Medicine at Hofstra/Northwell (US)
- National Institute of Neurological Disorders and Stroke (US)
- National Institute of Mental Health (US)
- Zucker Hillside Hospital (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2026-11-03
- DOI
- https://doi.org/10.1038/s41467-026-78783-4
- Primary Topic
- Autoimmune Neurological Disorders and Treatments
- Type
- article
- Field-Weighted Citation Impact
- 0.00