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.
Johann Steiner,Martin Walter,Wenzel Glanz,Zoltán Sarnyai,Hans-Gert Bernstein,Stefan Vielhaber,A. Kästner,Martin Skalej,Wolfgang Jordan,Kolja Schiltz,Christine Klingbeil,Klaus-Peter Wandinger,Bernhard Bogerts,Winfried Stoecker +13 more
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Acutely ill patients with an initial schizophrenia diagnosis show an increased prevalence of NMDA-R antibodies and the repertoire of antibody subtypes in schizophrenia and MD is different from that with NMda-R encephalitis.Abstract:
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 withanddistinctionfromthoseinNMDA-Rencephalitis. 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 -amino-3-hydroxyl-5-methyl-4-isoxazole-propionatereceptors(AMPA-R)(GluR1/GluR2)serumantibodieswere determined. Participants:Twohundredthirtymatchedhealthycontrols were compared with patients (unmedicated for at least6weeks)withschizophrenia(n=121),MD(n=70), or BLPD (n=38). Main Outcome Measures: The primary outcome was theoverallnumberofseropositivecasesforNMDA-Rand 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 classifiedashavingcatatonicordisorganizedschizophreniawere reclassified as having misdiagnosed NMDA-R encephalitis(presenceofspecificserumandcerebrospinalfluidIgG NR1a antibodies). In all other seropositive cases, the antibodies consisted of classes IgA and/or IgM or were directedagainstNR1a/NR2b(notagainstNR1aalone).None ofthepatientsorcontrolshadantibodiesagainstAMPA-R. Conclusions: Acutely ill patients with an initial schizophrenia diagnosis show an increased prevalence of NMDA-R antibodies. The repertoire of antibody subtypesinschizophreniaandMDisdifferentfromthatwith NMDA-Rencephalitis.Thelatterdisordershouldbeconsidered as a differential diagnosis, particularly in young females with acute disorganized behavior or catatonia.read more
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Analysis of shared heritability in common disorders of the brain
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TL;DR: Findings implicating the MHC region are consistent with an immune component to schizophrenia risk, whereas the association with NRGN and TCF4 points to perturbation of pathways involved in brain development, memory and cognition.
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