Increased autoantibodies against brain tissue in schizophrenia

Background: Patients with schizophrenia have increased levels of autoantibodies
against a range of proteins, such as NMDA receptor and heat shock proteins. We
tested whether schizophrenia patients manufacture increased antibodies against
brain proteins and how this may relate to clinical features.

Methods: We collected serum from 37 schizophrenia patients (21 men, mean age
34±7.6 years) and 33 controls (18 men, mean age 32±7.2 years). We used human serum as primary antibodies for immunohistochemistry on sagittal rat brain sections. Sections were scored on level of staining (1=low, 2=medium, 3=high staining) and on cellular sources of staining in the cerebellum and frontal cortex. Patients were rated for symptoms using PANSS and cognition was tested using WAIS-III and WMS-III.

Results: All human serum showed positive immunohistochemical reaction to
rat brain. Intensity of cerebellar staining was significantly increased with serum
from schizophrenia patients (Chi=8.95, p=0.03) relative to controls. Early age-ofonset was associated with greater intensity of staining of Purkinje neurons across all patients (rho=-.35, p=0.03). Greater neuronal/neuropil immunoreactivity in cerebellum and cortex was associated with higher symptom severity. In both groups, perinuclear immunoreactivity in frontal cortex was positively correlated with memory performance (rho=.30, p=0.01).

Conclusions: Schizophrenia patients and healthy controls manufacture
autoantibodies targeting brain proteins and this putative normal process may
be exaggerated in schizophrenia patients, especially toward cerebellar proteins.
Although autoantibodies against neurons may contribute subtle beneficial
effects on cognitive function, overproduction of brain antibodies may be
detrimental with respect to illness onset and psychotic symptoms in patients with schizophrenia.