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Prevalence of anti-N-methyl-d-aspartate (NMDA) receptor antibodies in patients with schizophrenia and related psychoses: a systematic review and meta-analysis‡

Published online by Cambridge University Press:  13 December 2013

T. A. Pollak ,
R. McCormack ,
M. Peakman ,
T. R. Nicholson  and
A. S. David
T. A. Pollak*
Affiliation:
National Institute for Health Research (NIHR) Biomedical Research Centre, South London and Maudsley NHS Foundation Trust and Institute of Psychiatry, King's College London, UK Section of Cognitive Neuropsychiatry, Department of Psychosis Studies, Institute of Psychiatry, King's College London, UK
R. McCormack
Affiliation:
National Institute for Health Research (NIHR) Biomedical Research Centre, South London and Maudsley NHS Foundation Trust and Institute of Psychiatry, King's College London, UK Section of Cognitive Neuropsychiatry, Department of Psychosis Studies, Institute of Psychiatry, King's College London, UK
M. Peakman
Affiliation:
Department of Immunobiology, King's College London, UK Biomedical Research Centre at Guy's and St Thomas' NHS Trust and King's College London, UK
T. R. Nicholson
Affiliation:
Section of Cognitive Neuropsychiatry, Department of Psychosis Studies, Institute of Psychiatry, King's College London, UK
A. S. David
Affiliation:
Section of Cognitive Neuropsychiatry, Department of Psychosis Studies, Institute of Psychiatry, King's College London, UK
*
* Address for correspondence: Dr T. A. Pollak, Section of Cognitive Neuropsychiatry, Institute of Psychiatry, De Crespigny Park, London SE5 8AF, UK. (Email: thomas.pollak@kcl.ac.uk)
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Abstract

Background

Anti-N-methyl-d-aspartate (NMDA) receptor encephalitis is an autoimmune condition caused by immunoglobulin (Ig)G antibodies directed against the NR1 subunit of the NMDA glutamate receptor. Approximately 65% of cases present with psychiatric symptoms, particularly psychosis. It remains to be established whether anti-NMDA receptor antibodies can cause a ‘purely’ psychotic illness without overt neurological symptoms.

Method

We conducted a systematic literature search to establish what proportion of patients with schizophrenia and related psychoses have antibodies directed against the NMDA receptor. Studies were included if (a) subjects had a diagnosis of schizophrenia, schizophrenia spectrum disorder or first-episode psychosis (FEP) using standard criteria, (b) serum was analysed for the presence of anti-NMDA receptor antibodies; and (c) the purpose of the study was to look for the presence of anti-NMDA receptor antibodies in patients with a primary psychiatric diagnosis without clinical signs of encephalitis.

Results

Seven studies were included, comprising 1441 patients, of whom 115 [7.98%, 95% confidence interval (CI) 6.69–9.50] were anti-NMDA receptor antibody positive. Of these, 21 (1.46%, 95% CI 0.94–2.23) patients were positive for antibodies of the IgG subclass. Prevalence rates were greater in cases than controls only for IgG antibodies; other subclasses are of less certain aetiological relevance. There was significant heterogeneity in terms of patient characteristics and the antibody assay used.

Conclusions

A minority of patients with psychosis are anti-NMDA receptor antibody positive. It remains to be established whether this subset of patients differs from antibody-negative patients in terms of underlying pathology and response to antipsychotic treatment, and whether immunomodulatory treatments are effective in alleviating psychotic symptoms in this group.

Keywords

AntibodyautoimmunityN-methyl-d-aspartate (NMDA) receptorpsychosisschizophrenia
Type
Review Article
Information
Psychological Medicine , Volume 44 , Issue 12 , September 2014 , pp. 2475 - 2487
Copyright
Copyright © Cambridge University Press 2013 

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