Current Findings on the Spectrum of Neuronal Autoantibodies Associated with Psychotic Disorders

Abstract

Background: Neural autoantibodies are observed in a subtype of psychotic disorders ranging from first-episode psychosis to schizophrenia. The clinical spectrum has so far been incompletely described, as new neuronal autoantibodies are emerging in the context of psychosis. This review is dedicated to describing the current spectrum of neural autoantibodies associated with psychotic disorders.
 Methods: In our narrative review, we searched for neural autoantibodies addressed in the PubMed database in the last 15 years focusing on the last three years after publication of the international guidelines for autoimmune psychosis. We relied on small and large cohort studies and case series descriptions related to neural autoantibodies in psychotic disorders.
 Results: Mainly neural autoantibodies against membrane surface structures such as N-Methyl-D-aspartate receptors (NMDAR) and against intracellular targets are present in psychotic disorders, but also in healthy controls. There is current suspicion that these neuronal autoantibodies (ie., NMDAR autoantibodies) play a potentially relevant role in the development of brain pathologies in psychotic disorders, especially when detected in cerebrospinal fluid. Autoantibodies against cell adhesion molecules and synaptic proteins such as neuronal cell adhesion molecule 1 (NCAM1) and antigen neurexin 1 alpha (NRXN1)-alpha occur in schizophrenia, but not in controls, suggesting that these are highly disease-specific antibodies. These lines of evidence are further supported by animal-model evidence showing a role of these autoantibodies in brain pathology and the development of schizophrenia-like symptoms.
 Conclusions: In recent years, a new landscape of potentially relevant neural autoantibodies has emerged in a subtype of psychotic disorders. Their significance remains unclear. Large-scale investigations should particularly investigate what triggers the pathogenicity of these autoantibodies, as they probably do not cause the psychotic disorder per se, but might be involved as one factor in the immunopathophysiology. Psychotic disorders remain elusive, and differential diagnosis is required to determine the role neural autoantibodies play in the manifestation of psychoses.

Neuronal autoantibodies in the cerebrospinal fluid of 148 patients with schizophrenia and 151 healthy controls

“…Approximately 90 % of the patients have prominent psychiatric or behavioral symptoms at onset [ 8 ], making it difficult to differentiate them from psychiatric disorders, particularly schizophrenia [ [9] , [10] , [11] , [12] ]. Other types of autoantibody encephalitis, such as paraneoplastic syndrome (PNS), are also known to cause psychiatric symptoms [ 13 , 14 ].…”