Identification of autoantibodies against L1CAM in patients with schizophrenia

Synaptic autoantibodies have been implicated in the pathophysiology of a subset of schizophrenia cases. The identification of novel autoantibodies in schizophrenia may therefore provide insights into previously unrecognized disease mechanisms. Here, we report the presence of autoantibodies against L1 cell adhesion molecule (L1CAM), a membrane protein expressed in neurons that contributes to cell adhesion and synapse formation. Using a cell-based assay, we analyzed 387 patients with schizophrenia and 362 healthy controls. Anti-L1CAM autoantibodies were detected in two patients with schizophrenia but not in healthy controls, and were also identified in the cerebrospinal fluid (CSF). Analysis using L1CAM deletion constructs indicated that the Ig1 domain of L1CAM is a major target of these autoantibodies. Administration of purified IgG from these patients into the CSF of mice was associated with impaired cognitive performance. Patients positive for anti-L1CAM autoantibodies also exhibited marked cognitive deficits. Together, these findings suggest that anti-L1CAM autoantibodies may be associated with disease mechanisms in a small subset of schizophrenia cases.