Research led by Tokyo Medical and Dental University suggests there could be an autoimmune cause for some types of schizophrenia, which if confirmed could result in more effective, targeted treatments for these patients.
Schizophrenia is a very heterogeneous condition, both genetically and symptomatically. Previous research has suggested there are several underlying mechanisms and that one could be linked to the immune system. Indeed, mutations in the immune regulatory MHC region of the genome carry some of the highest risk for developing schizophrenia.
Autoantibodies, which often signal the onset of an autoimmune condition, against neural cell adhesion molecule (NCAM)1 have been observed in some patients with schizophrenia.
In this study, published in Cell Reports Medicine, Hidehiko Takahashi, a professor at Tokyo Medical and Dental University, and colleagues tested a group of 223 patients with confirmed schizophrenia and 201 controls for the presence of anti-NCAM1 autoantibodies.
Two different tests were used; 15 patients with schizophrenia had anti-NCAM1 autoantibodies according to an ELISA assay and 12 according to a cell-based assay. None of the control group had anti-NCAM1 autoantibodies using the ELISA test and two had very low levels using the cell-based assay.
“There are several interpretations regarding autoantibodies in healthy individuals,” write the authors. “Various autoantibodies have been reported in healthy subjects, such as anti-NMDA receptor antibody, anti-CASPR2 antibody, and anti-amphiphysin antibody, which have all been established as causes of encephalitis. Whether these autoantibodies lead to the onset of neurological or psychiatric symptoms depends on their antibody titer and whether the autoantibodies reach the nervous system through the blood-brain barrier.”
The research team expanded their work into a mouse model and investigated the effects of these anti-NCAM1 autoantibodies on the physiology of the mice. They found that even after a short time, the mouse brains started to show changes very similar to those seen in humans with schizophrenia. The team found the antibodies induce “schizophrenia-related behavior in mice, including deficient pre-pulse inhibition and cognitive impairment.”
Takahashi and team emphasize the importance of identifying these autoantibodies, because they can serve as biomarkers that distinguish a subgroup of patients with schizophrenia.
Further validation and research is needed to confirm and expand these findings, but “immunological interventions such as plasma exchange and immunoglobulin therapy, which are usually used to treat autoantibody encephalitis, may work in this subgroup,” say the authors.
“A clinical study testing whether anti-NCAM1 autoantibodies play a role in schizophrenia would show [whether] interventions improve the symptoms of schizophrenia.”
