Acute schizophrenia shows increased NMDA-R antibody prevalence

By Liam Davenport, medwireNews Reporter

Patients with acute schizophrenia have an increased prevalence of N-methyl-D-aspartate glutamate receptor (NMDA-R) antibodies that is distinct from that seen in NMDA-R encephalitis, scientists have found.

"Our findings suggest that the repertoire of antibody classes and epitope targets is wider in patients with the psychiatric diagnoses of schizophrenia, MD [major depression], or BLPD [borderline personality disorder] than in patients with NMDA-R encephalitis, " say Johann Steiner (University of Magdeburg, Germany) and colleagues.

"The identification of a subcohort with NMDA-R antibodies may open the door to personalized medicine and render patients susceptible to new specific glutamate-modulating, anti-inflammatory, or immunomodulating therapies," they add.

As reported in JAMA Psychiatry, the team compared 121 patients admitted to hospital with acute schizophrenia who had been unmedicated for at least 6 weeks, 70 patients with MD, and 38 with BLPD, with 230 matched healthy controls.

The researchers found that 9.9% of schizophrenia patients had several types of NMDA-R serum antibodies. Specifically, they had immunoglobulin (Ig)A, IgG, and IgM class antibodies, directed against the NR1a subunit alone or against NR1a/2b. None of the BLPD patients were seropositive, while only 2.8% of MD patients and 0.4% of control individuals were seropositive.

Even taking into account two patients who were later reclassified as having NMDA-R encephalitis, there was a significant difference between groups in terms of seropositivity. There were no seasonal effects on the presence of NMDA-R antibodies.

IgG antibodies directed against NR1a were found in two patients with an initial diagnosis of disorganized or catatonic schizophrenia, and they were reclassified as having NMDA-R encephalitis. The two other individuals with IgG antibodies, which bound only to NR1a/NR2b, were diagnosed as having paranoid schizophrenia, and had substantially lower antibody titers. In all other patients, antibodies directed against NR1a alone were IgA and/or IgM subtypes.

Only the patients reclassified as having NMDA-R encephalitis had antibodies in their cerebrospinal fluid, which declined from 1:320 to 1:32 during remission. This was paralleled by reduced serum IgG NR1a antibodies.

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