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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TLDR
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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Allostatic load is associated with psychotic symptoms and decreases with antipsychotic treatment in patients with schizophrenia and first-episode psychosis
Maximus Berger,Robert-Paul Juster,Sabine Westphal,G. Paul Amminger,Bernhard Bogerts,Kolja Schiltz,Sabine Bahn,Johann Steiner,Zoltán Sarnyai,Zoltán Sarnyai +9 more
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Autoantibody-associated psychiatric symptoms and syndromes in adults: A narrative review and proposed diagnostic approach.
Niels Hansen,Michael Lipp,Jonathan Vogelgsang,Ruth Vukovich,Tristan Zindler,Daniel Luedecke,Stefan Gingele,Berend Malchow,Helge Frieling,Simone Kühn,Johannes Denk,Jürgen Gallinat,Thomas Skripuletz,Nicole Moschny,Jens Fiehler,Christian Heiner Riedel,Klaus Wiedemann,Mike P. Wattjes,Inga Zerr,Inga Zerr,Hermann Esselmann,Stefan Bleich,Jens Wiltfang,Jens Wiltfang,Jens Wiltfang,Alexandra Neyazi +25 more
TL;DR: A diagnostic approach to optimize the detection of autoantibodies in psychiatric patients, potentially leading to the approval of an immunotherapy, and develops a clinical diagnostic pathway for classifying subgroups of psychiatric patients whose psychiatric symptoms indicate a suspected autoimmune origin.
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