Is schizophrenia an autoimmune disease?

The concept that psychiatric diseases such as depression and schizophrenia might have an immune component dates back at least 40 years, with numerous studies providing evidence implicating the immune system and autoimmune responses at least in some patients with these diseases. Various “anti-brain cell antibodies” have been reported but lacking to date has been a clear understanding of what autoantibodies typify psychiatric diseases and how engagement of their targets cause disease.

In the current issue of Lancet Psychiatry, Lennox and colleagues describe a search for neuronal cell specific autoantibodies in patients with first-episode psychosis. They took advantage of a panel of live-cell assays developed in Oxford to specifically detect autoantibodies against complex neuronal surface proteins. Only one assay in the panel showed differences between patients and healthy controls – antibodies against the N-methyl-D-aspartate receptor (NMDAR) were found in 3% of those presenting with psychosis but none of the controls. There was no obvious difference in disease between those with and without anti-NMADR antibodies.

NMDAR is an important receptor for normal neuronal function, playing key roles in learning and memory among other important activities. Autoantibodies against NMADR have previously been described in association with other brain diseases, notably encephalitis, and implicated in the disease process. The demonstration that a subset of patients presenting with psychosis have anti-NMDAR autoantibodies supports the concept that at least some cases of psychosis represent an autoimmune attack on brain cells. The finding raises the possibility of treating “autoimmune psychosis” in ways currently used for other autoimmune diseases – by targeting the autoantibodies and immune cells responsible.

This work is an exciting step towards the biological stratification of psychiatric disorders and points the way towards new immune-based treatments for some patients. Before leaping in with antibody elimination or immune cell ablation therapies, there is a clear need to replicate this study in other (larger) patient groups and to extend the range of autoantibodies screened for. Nevertheless, the work raises the possibility that autoantibody screening tests will enable the identification of a proportion of early psychosis patients suitable for such interventions – finally, a therapy that tackles cause in a psychiatric disease.

Jeremy Hall and Paul Morgan are Co-Directors of the newly created Hodge Centre for Neuropsychiatric Immunology, a research centre embedded in two Cardiff University Research Institutes that seeks to discover links between immunity/inflammation and psychiatric diseases.