Clinical, cognitive and neuroanatomical associations of serum NMDAR autoantibodies in people at clinical high risk for psychosis
Pollak, Thomas A. (King's College London. Department of Psychosis Studies)
Kempton, Matthew J. (King's College London. Department of Psychosis Studies)
Iyegbe, Conrad (King's College London. Department of Psychosis Studies)
Vincent, Angela (John Radcliffe Hospital (Oxford, Regne Unit))
Irani, Sarosh R. (John Radcliffe Hospital (Oxford, Regne Unit))
Coutinho, Ester (King's College London. Institute of Psychiatry, Psychology & Neuroscience)
Menassa, David A. (John Radcliffe Hospital (Oxford, Regne Unit))
Jacobson, Leslie (John Radcliffe Hospital (Oxford, Regne Unit))
de Haan, Lieuwe (University of Amsterdam. Department Early Psychosis)
Ruhrmann, Stephan (University of Cologne. Department of Psychiatry and Psychotherapy)
Sachs, Gabriele (Medical University of Vienna. Department of Psychiatry and Psychotherapy)
Riecher-Rössler, Anita (University of Basel. Medical Faculty)
Krebs, Marie-Odile (University of Paris. Institut de Psychiatrie)
Amminger, Paul (University of Melbourne. Centre for Youth Mental Health)
Glenthøj, Birte (University of Copenhagen. Centre for Neuropsychiatric Schizophrenia Research & Centre for Clinical Intervention and Neuropsychiatric Schizophrenia Research)
Barrantes-Vidal, Neus (Universitat Autònoma de Barcelona. Departament de Psicologia Clínica i de la Salut)
van Os, Jim (Maastricht University Medical Centre. Department of Psychiatry and Neuropsychology)
Rutten, Bart P. F. (Maastricht University Medical Centre. Department of Psychiatry and Neuropsychology)
Bressan, Rodrigo Affonseca (Universidade Federal de São Paulo. Institute for Prevention of Mental Disorders)
van der Gaag, Mark (VU University. Department of Clinical Psychology)
Yolken, Robert (Johns Hopkins School of Medicine. Department of Pediatrics)
Hotopf, Matthew (King's College London. Department of Psychological Medicine)
Valmaggia, Lucia (King's College London. Institute of Psychiatry, Psychology & Neuroscience)
Stone, James (King's College London. Department of Psychosis Studies)
David, Anthony S. (King's College London. Department of Psychosis Studies)
McGuire, Philip (King's College London. Department of Psychosis Studies)

Date:	2020
Abstract:	Serum neuronal autoantibodies, such as those to the NMDA receptor (NMDAR), are detectable in a subgroup of patients with psychotic disorders. It is not known if they are present before the onset of psychosis or whether they are associated with particular clinical features or outcomes. In a case-control study, sera from 254 subjects at clinical high risk (CHR) for psychosis and 116 healthy volunteers were tested for antibodies against multiple neuronal antigens implicated in CNS autoimmune disorders, using fixed and live cell-based assays (CBAs). Within the CHR group, the relationship between NMDAR antibodies and symptoms, cognitive function and clinical outcomes over 24 month follow-up was examined. CHR subjects were not more frequently seropositive for neuronal autoantibodies than controls (8. 3% vs. 5. 2%; OR = 1. 50; 95% CI: 0. 58-3. 90). The NMDAR was the most common target antigen and NMDAR IgGs were more sensitively detected with live versus fixed CBAs (p < 0. 001). Preliminary phenotypic analyses revealed that within the CHR sample, the NMDAR antibody seropositive subjects had higher levels of current depression, performed worse on the Rey Auditory Verbal Learning Task (p < 0. 05), and had a markedly lower IQ (p < 0. 01). NMDAR IgGs were not more frequent in subjects who later became psychotic than those who did not. NMDAR antibody serostatus and titre was associated with poorer levels of functioning at follow-up (p < 0. 05) and the presence of a neuronal autoantibody was associated with larger amygdala volumes (p < 0. 05). Altogether, these findings demonstrate that NMDAR autoantibodies are detectable in a subgroup of CHR subjects at equal rates to controls. In the CHR group, they are associated with affective psychopathology, impairments in verbal memory, and overall cognitive function: these findings are qualitatively and individually similar to core features of autoimmune encephalitis and/or animal models of NMDAR antibody-mediated CNS disease. Overall the current work supports further evaluation of NMDAR autoantibodies as a possible prognostic biomarker and aetiological factor in a subset of people already meeting CHR criteria.
Grants:	European Commission 241909 Agència de Gestió d'Ajuts Universitaris i de Recerca 2017-SGR-1612
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Schizophrenia ; Neuroscience ; Prognostic markers
Published in:	Molecular psychiatry, Vol. 26 (october 2020) , p. 2590-2604, ISSN 1476-5578

DOI: 10.1038/s41380-020-00899-w
PMID: 33077853

15 p, 1.4 MB

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