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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Immune system and glucose metabolism interaction in schizophrenia: a chicken-egg dilemma.
Johann Steiner,Hans-Gert Bernstein,Kolja Schiltz,Ulf J. Müller,Sabine Westphal,Hemmo A. Drexhage,Bernhard Bogerts +6 more
TL;DR: It is currently unclear whether impaired cerebral glucose utilization leads to secondary disturbances in peripheral glucose metabolism, an increased risk of cardiovascular complications, and accompanying pro-inflammatory changes in patients with schizophrenia or whether immune mechanisms may be involved in the initial pathogenesis of schizophrenia, which leads to disturbances in glucose metabolism such as metabolic syndrome.
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NMDA Receptor Internalization by Autoantibodies: A Reversible Mechanism Underlying Psychosis?
TL;DR: Data supporting or refuting the possibility that this disorder or similar autoimmune disorders affecting synaptic proteins, which are therefore treatable with immunomodulation, could account for some cases of idiopathic psychosis are reviewed.
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Preexisting Serum Autoantibodies Against the NMDAR Subunit NR1 Modulate Evolution of Lesion Size in Acute Ischemic Stroke
Maria Zerche,Karin Weissenborn,Christoph Ott,Ekrem Dere,Abdul R. Asif,Hans Worthmann,Imam Hassouna,Kristin Rentzsch,Anita B. Tryc,Liane Dahm,Johann Steiner,Lutz Binder,Jens Wiltfang,Anna-Leena Sirén,Winfried Stöcker,Hannelore Ehrenreich +15 more
TL;DR: Dependence on blood–brain barrier integrity before an acute ischemic brain injury, preexisting NMDAR1 autoantibodies seem to be beneficial or detrimental.
Journal ArticleDOI
Molecular and cellular mechanisms underlying anti-neuronal antibody mediated disorders of the central nervous system.
M.H. van Coevorden-Hameete,E. de Graaff,Maarten J. Titulaer,Casper C. Hoogenraad,P. A. E. Sillevis Smitt +4 more
TL;DR: This review shows that antibodies to neuronal surface antigens are often directed at conformational epitopes located in the extracellular domain of the antigen, which may explain the distinct clinical phenotypes that are seen in patients with antibodies to antigen that are expressed throughout the brain.
Journal ArticleDOI
Anti-N-Methyl-D-aspartate Receptor Encephalitis: A Severe, Potentially Reversible Autoimmune Encephalitis.
TL;DR: Recent studies have clearly documented that both clinical manifestations and the antibodies may contribute to early diagnosis and multidisciplinary care in anti-NMDAR encephalitis, and clinicians should be aware of the overlapping diseases.
References
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TL;DR: These data indicate that N-methyl-D-aspartate antagonists produce a broad range of symptoms, behaviors, and cognitive deficits that resemble aspects of endogenous psychoses, particularly schizophrenia and dissociative states.
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Dementia praecox and paraphrenia
TL;DR: "Dementia Praecox and Paraphrenia" (1919) was the book in which Kraepelin first presented his work on schizophrenia to the English-speaking world, and it was probably the most influential psychiatric text of the entire 20th century, and has now become rare.
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