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Brain-relevant antibodies in first-episode psychosis: a matched case–control study

Published online by Cambridge University Press:  18 September 2017

Fiona Gaughran
National Psychosis Service, South London and Maudsley NHS Foundation Trust The Collaboration for Leadership in Applied Health Research and Care (CLAHRC), South London Psychosis Research Team, London, UK Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK
John Lally*
Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK Department of Psychiatry, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin, Ireland Department of Psychiatry, School of Medicine and Medical Sciences, University College Dublin, and St Vincent's University Hospital, Dublin, Ireland
Katherine Beck
Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK
Ruaidhri McCormack
Addenbrooke's Hospital, Cambridge, UK
Poonam Gardner-Sood
Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK
Ester Coutinho
Nuffield Department of Clinical Neurosciences, Oxford University Hospitals, University of Oxford, Oxford, UK
Leslie Jacobson
Nuffield Department of Clinical Neurosciences, Oxford University Hospitals, University of Oxford, Oxford, UK
Bethan Lang
Nuffield Department of Clinical Neurosciences, Oxford University Hospitals, University of Oxford, Oxford, UK
Ricardo Sainz-Fuertes
Basic and Clinical Neuroscience at the Institute of Psychiatry, Psychology, & Neuroscience, King's College London, London, UK
Evangelos Papanastasiou
Cognition Schizophrenia and Imaging Laboratory (CSI Lab), Department of Psychosis Studies, Institute of Psychiatry Psychology and Neuroscience, King's College London, London, UK
Marta Di Forti
SGDP, Institute of Psychiatry, Psychology and Neuroscience, King's College London, and South London and Maudsley NHS Foundation Trust, London, UK
Tim Nicholson
Section of Cognitive Neuropsychiatry, Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK
Angela Vincent
Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford, UK
Robin M. Murray
National Psychosis Service, South London and Maudsley NHS Foundation Trust Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK
Author for correspondence: Dr John Lally, E-mail:



There has been much recent excitement about the possibility that some cases of psychosis may be wholly due to brain-reactive antibodies, with antibodies to N-methyl-D-aspartate receptor (NMDAR) and the voltage-gated potassium channel (VGKC)-complex reported in a few patients with first-episode psychosis (FEP).


Participants were recruited from psychiatric services in South London, UK, from 2009 to 2011 as part of the Genetics and Psychosis study. We conducted a case–control study to examine NMDAR and VGKC-complex antibody levels and rates of antibody positivity in 96 patients presenting with FEP and 98 controls matched for age and sex. Leucine-rich glioma inactiviated-1 (LGI1) and contactin-associated protein (CASPR) antibodies were also measured. Notably, patients with suspicion of organic disease were excluded.


VGKC-complex antibodies were found in both cases (n = 3) and controls (n = 2). NMDAR antibody positivity was seen in one case and one control. Either LGI1-Abs or CASPR2-Abs were found in three cases and three controls. Neuronal antibody staining, consistent with the above results or indicating potential novel antigens, was overall positive in four patients but also in six controls. Overall, antibody positivity was at low levels only and not higher in cases than in controls.


This case–control study of the prevalence of antibodies in FEP does not provide evidence to support the hypothesis that FEP is associated with an immune-mediated process in a subgroup of patients. Nevertheless, as other bio-clinical factors may influence the effect of such antibodies in a given individual, and patients with organic neurological disease may be misdiagnosed as FEP, the field requires more research to put these findings in context.

Original Articles
Copyright © Cambridge University Press 2017 

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These authors contributed equally to the paper and are joint first authors.

These authors contributed equally to the paper and should be acknowledged as joint last authors.


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