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Fact or Fiction? Examining a Role for N-Methyl-D-Aspartate Receptor Autoantibodies in Psychiatric Illness

  • Matthew S. Kayser
    Correspondence
    Address correspondence to Matthew S. Kayser, M.D., Ph.D., Perelman School of Medicine at the University of Pennsylvania, 10-160 Translational Research Center, 3400 Civic Center Boulevard, Building 421, Philadelphia, PA 19104-5158
    Affiliations
    Departments of Psychiatry and Neuroscience, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
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      There is a pressing need in psychiatry to establish biologically based disease subtypes, which might allow for more specific diagnosis and effective intervention. An active area of investigation in this realm has been autoimmunity and mental illness. The discovery and characterization of anti–N-methyl-D-aspartate receptor (NMDAR) encephalitis has led the resurgent effort into understanding whether specific autoantibody syndromes might define a subset of patients with psychiatric diagnoses or symptoms, such as schizophrenia or psychosis. Numerous groups have attempted to detect disease-causing autoantibodies in adults; in this issue of Biological Psychiatry, Pathmanandavel et al. (
      • Pathmanandavel K.
      • Starling J.
      • Merheb V.
      • Ramanathan S.
      • Sinmaz N.
      • Dale R.C.
      • Brilot F.
      Antibodies to surface dopamine-2 receptor and N-methyl-D-aspartate receptor in the first episode of acute psychosis in children.
      ) take an important step in searching for autoantibodies associated with a first episode of psychosis in a pediatric population.
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      Linked Article

      • Antibodies to Surface Dopamine-2 Receptor and N-Methyl-D-Aspartate Receptor in the First Episode of Acute Psychosis in Children
        Biological PsychiatryVol. 77Issue 6
        • Preview
          The dopamine and glutamate hypotheses are well known in psychosis. Recently, the detection of autoantibodies against proteins expressed on the surface of cells in the central nervous system has raised the possibility that specific immune-mediated mechanisms may define a biological subgroup within psychosis, although no cohort of a first episode of psychosis in children has been investigated.
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      • N-Methyl-D-Aspartate Receptor Autoantibodies in Psychiatric Illness
        Biological PsychiatryVol. 79Issue 9
        • Preview
          We would like to respond to the comments made in a recent editorial (1) concerning the article by Pathmanandavel et al. (2). We agree the technique for detection of N-methyl-D-aspartate receptor (NMDAR) autoantibodies is critical and that cerebrospinal fluid is a useful material for identifying patients with classic “anti-NMDAR” encephalitis. However, the cell-based assays that Kayser (1) refers to can be done either with live cells or with permeabilized/fixed human embryonic kidney cells expressing NMDAR subunits (NR1 with or without NR2B).
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