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

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Version 2 2021-09-02, 15:16
Version 1 2019-11-22, 17:09
journal contribution
posted on 2021-09-02, 15:16 authored by Fiona Gaughran, John LallyJohn Lally, Katherine Beck, Ruaidhri McCormack, Poonam Gardner-Sood, Ester Coutinho, Leslie Jacobson, Bethan Lang, Ricardo Sainz-Fuertes, Evangelos Papanastasiou, Marta Di Forti, Tim Nicholson, Angela Vincent, Robin M. Murray

BACKGROUND: 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).

METHODS: 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.

RESULTS: 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.

CONCLUSIONS: 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.


This paper summarises independent research funded by the National Institute for Health Research (NIHR) under its IMPACT Programme (Grant Reference Number RP-PG-0606-1049) and by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London. F.G. is supported by the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care South London at King’s College Hospital NHS Foundation Trust Work in the Oxford laboratory is supported partly by the NIHR Oxford Biomedical Centre. The views expressed are those of the authors and not necessarily those of the National Health Service (NHS), the NIHR or the Department of Health. F.G. is also supported by the South London CLAHRC.



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Published Citation

Gaughran F, Lally J, Beck K, McCormack R, Gardner-Sood P, Coutinho E, Jacobson L, Lang B, Sainz-Fuertes R, Papanastasiou E, Di Forti M, Nicholson T, Vincent A, Murray RM. Brain-relevant antibodies in first-episode psychosis: a matched case-control study. Psychological Medicine. 2017;1-9.

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  • Beaumont Hospital
  • Psychiatry

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