Document Detail

Increased prevalence of diverse N-methyl-D-aspartate glutamate receptor antibodies in patients with an initial diagnosis of schizophrenia: specific relevance of IgG NR1a antibodies for distinction from N-methyl-D-aspartate glutamate receptor encephalitis.
MedLine Citation:
PMID:  23344076     Owner:  NLM     Status:  MEDLINE    
CONTEXT: Evidence for symptomatic convergence of schizophrenia and N-methyl-D-aspartate glutamate receptor (NMDA-R) encephalitis highlights the need for an assessment of antibody prevalence and specificity for distinct disease mechanisms in patients with a diagnosis of schizophrenia among glutamatergic pathophysiologic abnormalities in psychiatric disorders.
OBJECTIVES: To compare the specificity and prevalence of NMDA-R antibodies in schizophrenia (DSM-IV criteria) with those of other psychiatric diagnoses and to determine whether antibody subtypes characterize overlap with and distinction from those in NMDA-R encephalitis.
DESIGN: Serum from 459 patients admitted with acute schizophrenia, major depression (MD), and borderline personality disorder (BLPD) or individuals serving as matched controls was obtained from our scientific blood bank. To explore epitope specificity and antibody subtype, IgA/IgG/IgM NMDA-R (NR1a or NR1a/NR2b) and α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptors (AMPA-R) (GluR1/GluR2) serum antibodies were determined.
PARTICIPANTS: Two hundred thirty matched healthy controls were compared with patients (unmedicated for at least 6 weeks) with schizophrenia (n = 121), MD (n = 70), or BLPD (n = 38).
MAIN OUTCOME MEASURES: The primary outcome was the overall number of seropositive cases for NMDA-R and AMPA-R antibodies; the secondary outcome was disease specificity of IgA/IgG/IgM antibodies and epitope specificity for clinical subgroups.
RESULTS: Diverse NMDA-R antibodies were identified in 15 subjects, primarily those with an initial schizophrenia diagnosis (9.9%), opposed to MD (2.8%), BLPD (0), and controls (0.4%). Retrospectively, 2 patients initially classified as having catatonic or disorganized schizophrenia were reclassified as having misdiagnosed NMDA-R encephalitis (presence of specific serum and cerebrospinal fluid IgG NR1a antibodies). In all other seropositive cases, the antibodies consisted of classes IgA and/or IgM or were directed against NR1a/NR2b (not against NR1a alone). None of the patients or controls had antibodies against AMPA-R.
CONCLUSIONS: Acutely ill patients with an initial schizophrenia diagnosis show an increased prevalence of NMDA-R antibodies. The repertoire of antibody subtypes in schizophrenia and MD is different from that with NMDA-R encephalitis. The latter disorder should be considered as a differential diagnosis, particularly in young females with acute disorganized behavior or catatonia.
Johann Steiner; Martin Walter; Wenzel Glanz; Zoltán Sarnyai; Hans-Gert Bernstein; Stefan Vielhaber; Andrea Kästner; Martin Skalej; Wolfgang Jordan; Kolja Schiltz; Christine Klingbeil; Klaus-Peter Wandinger; Bernhard Bogerts; Winfried Stoecker
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  JAMA psychiatry     Volume:  70     ISSN:  2168-6238     ISO Abbreviation:  JAMA Psychiatry     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-03-07     Completed Date:  2013-05-02     Revised Date:  2013-12-13    
Medline Journal Info:
Nlm Unique ID:  101589550     Medline TA:  JAMA Psychiatry     Country:  United States    
Other Details:
Languages:  eng     Pagination:  271-8     Citation Subset:  AIM; IM    
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MeSH Terms
Autoantibodies / blood*
Borderline Personality Disorder / diagnosis,  immunology
Case-Control Studies
Depressive Disorder, Major / diagnosis,  immunology
Encephalitis / diagnosis,  immunology
Immunoglobulin G / blood*
Immunoglobulins / blood
Middle Aged
Receptors, AMPA / immunology*
Receptors, N-Methyl-D-Aspartate / immunology*
Schizophrenia* / diagnosis,  immunology
Sensitivity and Specificity
Reg. No./Substance:
0/Autoantibodies; 0/Immunoglobulin G; 0/Immunoglobulins; 0/NR1A protein, human; 0/NR2B NMDA receptor; 0/Receptors, AMPA; 0/Receptors, N-Methyl-D-Aspartate; 0/glutamate receptor ionotropic, AMPA 1; 0/glutamate receptor ionotropic, AMPA 2

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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