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Antibody-mediated encephalitis and psychosis

Published online by Cambridge University Press:  02 January 2018

T. A. Pollak
Affiliation:
Division of Psychological Medicine, Institute of Psychiatry, King's College London, De Crespigny Park, London SE5 8AF, UK. Email: thomas.pollak@kcl.ac.uk
B. R. Lennox
Affiliation:
Department of Psychiatry, University of Cambridge
A. Vincent
Affiliation:
Department of Clinical Neurology, University of Oxford, John Radcliffe Hospital, Oxford
T. R. Nicholson
Affiliation:
Division of Psychological Medicine, Institute of Psychiatry, King's College London, UK
Corresponding
E-mail address:
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Abstract

Type
Columns
Copyright
Copyright © Royal College of Psychiatrists, 2012 

The four cases of N-methyl-D-aspartate (NMDA) receptor antibody encephalitis with associated psychosis reported in December Reference Barry, Hardiman, Healy, Keogan, Moroney and Molnar1 raise an important and emerging issue and highlight that psychiatrists should include the condition in the differential diagnosis for patients presenting with acute psychosis. But there are some aspects that need clarification. The authors state that ‘this case series demonstrates a new and treatable cause of psychosis’, inferring that the association of psychosis with these antibodies was previously unknown. However, since the first 100 patients with NMDA receptor antibody encephalitis were reported in 2008, Reference Dalmau, Gleichman, Hughes, Rossi, Peng and Lai2 this association has been well documented; psychosis is typically the first presentation and many cases were seen by psychiatrists before neurologists become involved. Reference Dalmau, Gleichman, Hughes, Rossi, Peng and Lai2,Reference Lennox, Coles and Vincent3

The association of these antibodies with psychosis is highly relevant because they bind to key neuronal surface proteins and are therefore likely to be pathogenic. Indeed, NMDA receptor antibody encephalitis is a condition that responds to immunotherapy and, importantly, there is thought to be an initial ‘treatment window’ for optimal immunomodulation. Reference Irani, Bera, Waters, Zuliani, Maxwell and Zandi4,Reference Vincent, Bie, Irani and Waters5 The authors Reference Barry, Hardiman, Healy, Keogan, Moroney and Molnar1 speculate that ‘there may be a pure psychiatric presentation associated with lower antibody titres’. Indeed, a recent study found that 3 out of 46 patients with first-episode psychosis (with no neurological or other clinically distinguishing features) had NMDA receptor antibodies. Reference Zandi, Irani, Lang, Waters, Jones and McKenna6 One patient made a significant clinical improvement with plasmapheresis and steroid treatment. An additional patient had voltage-gated potassium channel antibodies, which can also be found in patients with other psychiatric presentations. Reference Vincent, Bie, Irani and Waters5,Reference Spinazzi, Argentiero, Zuliani, Palmieri, Tavolato and Vincent7 It now appears increasingly likely that other neuropsychiatric (e.g. catatonia) and psychiatric (e.g. obsessive-compulsive) symptoms may be associated with cell-surface neuronal antibodies. Reference Kayser, Kohler and Dalmau8

As Barry et al Reference Barry, Hardiman, Healy, Keogan, Moroney and Molnar1 point out, the condition does indeed provide some support for the NMDA receptor hypofunction hypothesis for psychosis. Some proponents of this theory have linked NMDA receptor hypofunction to first-rank psychotic symptoms in particular. Reference Stephan, Friston and Frith9 It is important that future studies of auto-antibody-associated psychosis characterise symptomatology in full, as this could allow for a level of clinical-pathological correlation rarely attained in psychiatry.

Footnotes

Declaration of interest

T.R.N. is supported by the Medical Research Council. T.A.P. and B.R.L. receive support from the National Institute for Health Research. A.V. receives royalties from Athena Diagnostics. A.V. and the Nuffield Department of Clinical Neurosciences in Oxford receive royalties and payments for antibody assays. B.R.L. and A.V. have written an editorial on this topic published in the February issue of the Journal.

References

1 Barry, H, Hardiman, O, Healy, DG, Keogan, M, Moroney, J, Molnar, PP, et al. Anti-NMDA receptor encephalitis: an important differential diagnosis in psychosis. Br J Psychiatry 2011; 199: 508–9.CrossRefGoogle ScholarPubMed
2 Dalmau, J, Gleichman, AJ, Hughes, EG, Rossi, JE, Peng, X, Lai, M, et al. Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies. Lancet Neurol 2008; 7: 1091–8.CrossRefGoogle ScholarPubMed
3 Lennox, BR, Coles, AJ, Vincent, A. Antibody-mediated encephalitis: a treatable cause of schizophrenia. Br J Psychiatry 2012; 200: 92–4.CrossRefGoogle ScholarPubMed
4 Irani, SR, Bera, K, Waters, P, Zuliani, L, Maxwell, S, Zandi, MS, et al. N-methyl-D-aspartate antibody encephalitis: temporal progression of clinical and paraclinical observations in a predominantly non-paraneoplastic disorder of both sexes. Brain 2010; 133: 1655–67.CrossRefGoogle Scholar
5 Vincent, A, Bie, CG, Irani, SR, Waters, P. Autoantibodies associated with diseases of the CNS: new developments and future challenges. Lancet Neurol 2011; 10: 759–72.CrossRefGoogle ScholarPubMed
6 Zandi, MS, Irani, SR, Lang, B, Waters, P, Jones, PB, McKenna, P, et al. Disease-relevant autoantibodies in first episode schizophrenia. J Neurol 2011; 258: 686–8.CrossRefGoogle ScholarPubMed
7 Spinazzi, M, Argentiero, V, Zuliani, L, Palmieri, A, Tavolato, B, Vincent, A. Immunotherapy-reversed compulsive, monoaminergic, circadian rhythm disorder in Morvan syndrome. Neurology 2008; 71: 2008–10.CrossRefGoogle ScholarPubMed
8 Kayser, MS, Kohler, CG, Dalmau, J. Psychiatric manifestations of paraneoplastic disorders. Am J Psychiatry 2010; 167: 1039–50.CrossRefGoogle ScholarPubMed
9 Stephan, KE, Friston, KJ, Frith, CD. Dysconnection in schizophrenia: from abnormal synaptic plasticity to failures of self-monitoring. Schizophr Bull 2009; 35: 509–27.CrossRefGoogle ScholarPubMed
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