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Prevalence and clinical characteristics of serum neuronal cell surface antibodies in first-episode psychosis: a case-control study

Prevalence and clinical characteristics of serum neuronal cell surface antibodies in first-episode psychosis: a case-control study
Prevalence and clinical characteristics of serum neuronal cell surface antibodies in first-episode psychosis: a case-control study
Background. Psychosis is a common presenting feature in antibody-mediated encephalitis, for which prompt recognition and treatment usually leads to remission. We aimed to investigate whether people with circumscribed schizophrenia-like illnesses have such antibodies—especially antibodies against the N-methyl-D-aspartate receptor (NMDAR)—more commonly than do healthy controls.

Methods. We recruited patients aged 14–35 years presenting to any of 35 mental health services sites across England with first-episode psychosis, less than 6 weeks of treatment with antipsychotic medication, and a score of 4 or more on at least one selected Positive and Negative Syndrome Scale (PANSS) item. Patients and controls provided venous blood samples. We completed standardised symptom rating scales (PANSS, ACE-III, GAF) at baseline, and tested serum samples for antibodies against NMDAR, LGI1, CASPR2, the GABAA receptor, and the AMPA receptor using live cell-based assays. Treating clinicians assessed outcomes of ICD diagnosis and functioning (GAF) at 6 months. We included healthy controls from the general population, recruited as part of another study in Cambridge, UK.

Findings Between Feb 1, 2013, and Aug 31, 2014, we enrolled 228 patients with first-episode psychosis and 105 healthy controls. 20 (9%) of 228 patients had serum antibodies against one or more of the neuronal cell surface antibodies compared with four (4%) of 105 controls (unadjusted odds ratio 2·4, 95% CI 0·8–7·3). These associations remained non-significant when adjusted for current cigarette smoking, alcohol consumption, and illicit drug use. Seven (3%) patients had NMDAR antibodies compared with no controls (p=0·0204). The other antibodies did not differ between
groups. Antibody-positive patients had lower PANSS positive, PANSS total, and catatonia scores than did antibodynegative patients. Patients had comparable scores on other PANSS items, ACE-III, and GAF at baseline, with no difference in outcomes at 6 months.

Interpretation Some patients with first-episode psychosis had antibodies against NMDAR that might be relevant to their illness, but did not differ from patients without NMDAR antibodies in clinical characteristics. Our study suggests that the only way to detect patients with these potentially pathogenic antibodies is to screen all patients with first-episode psychosis at first presentation.
2215-0366
42–48
Lennox, Belinda R.
8e9c73f8-4ce7-4787-92f2-a382833807f9
Palmer-Cooper, Emma C.
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Pollak, Thomas
64495e5a-d02f-41d1-920a-80edcd713915
Hainsworth, Jane
61dca3f5-763c-4980-86b5-d5b3e804fdcb
Marks, Jacqui
77538519-a1c9-4df4-a927-47a188442bba
Jacobson, Leslie
1ea2b155-f0ab-4be5-9f81-06fc77df00a4
Lang, Bethan
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Fox, Hannah
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Ferry, Berne
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Scoriels, Linda
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Crowley, Hannah
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Jones, Peter B.
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Harrison, Paul J.
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Vincent, Angela
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PPiP study team
Lennox, Belinda R.
8e9c73f8-4ce7-4787-92f2-a382833807f9
Palmer-Cooper, Emma C.
e96e8cb6-2221-4dc7-b556-603f2cf6b086
Pollak, Thomas
64495e5a-d02f-41d1-920a-80edcd713915
Hainsworth, Jane
61dca3f5-763c-4980-86b5-d5b3e804fdcb
Marks, Jacqui
77538519-a1c9-4df4-a927-47a188442bba
Jacobson, Leslie
1ea2b155-f0ab-4be5-9f81-06fc77df00a4
Lang, Bethan
ebdbe496-cc0c-4aeb-a5dc-380d6a786686
Fox, Hannah
b9d7b2f1-cecb-48ba-b034-310ba5596770
Ferry, Berne
c4e36389-228a-4857-8725-8ef766822486
Scoriels, Linda
e636b85d-c8a3-4ea0-b671-9b9ad35bedd8
Crowley, Hannah
46555c84-e29c-4c8a-899c-f17912327f23
Jones, Peter B.
1dd06b59-ee98-47e4-b291-e937657bed38
Harrison, Paul J.
b1a7c194-b9fa-4a31-ac89-0c253bbdfc9a
Vincent, Angela
6322745b-5633-4494-9c4f-64f86a7d7267

Lennox, Belinda R., Palmer-Cooper, Emma C., Pollak, Thomas, Hainsworth, Jane, Marks, Jacqui, Jacobson, Leslie, Lang, Bethan, Fox, Hannah, Ferry, Berne, Scoriels, Linda, Crowley, Hannah, Jones, Peter B., Harrison, Paul J. and Vincent, Angela , PPiP study team (2017) Prevalence and clinical characteristics of serum neuronal cell surface antibodies in first-episode psychosis: a case-control study. Lancet Psychiatry, 4 (1), 42–48. (doi:10.1016/S2215-0366(16)30375-3).

Record type: Article

Abstract

Background. Psychosis is a common presenting feature in antibody-mediated encephalitis, for which prompt recognition and treatment usually leads to remission. We aimed to investigate whether people with circumscribed schizophrenia-like illnesses have such antibodies—especially antibodies against the N-methyl-D-aspartate receptor (NMDAR)—more commonly than do healthy controls.

Methods. We recruited patients aged 14–35 years presenting to any of 35 mental health services sites across England with first-episode psychosis, less than 6 weeks of treatment with antipsychotic medication, and a score of 4 or more on at least one selected Positive and Negative Syndrome Scale (PANSS) item. Patients and controls provided venous blood samples. We completed standardised symptom rating scales (PANSS, ACE-III, GAF) at baseline, and tested serum samples for antibodies against NMDAR, LGI1, CASPR2, the GABAA receptor, and the AMPA receptor using live cell-based assays. Treating clinicians assessed outcomes of ICD diagnosis and functioning (GAF) at 6 months. We included healthy controls from the general population, recruited as part of another study in Cambridge, UK.

Findings Between Feb 1, 2013, and Aug 31, 2014, we enrolled 228 patients with first-episode psychosis and 105 healthy controls. 20 (9%) of 228 patients had serum antibodies against one or more of the neuronal cell surface antibodies compared with four (4%) of 105 controls (unadjusted odds ratio 2·4, 95% CI 0·8–7·3). These associations remained non-significant when adjusted for current cigarette smoking, alcohol consumption, and illicit drug use. Seven (3%) patients had NMDAR antibodies compared with no controls (p=0·0204). The other antibodies did not differ between
groups. Antibody-positive patients had lower PANSS positive, PANSS total, and catatonia scores than did antibodynegative patients. Patients had comparable scores on other PANSS items, ACE-III, and GAF at baseline, with no difference in outcomes at 6 months.

Interpretation Some patients with first-episode psychosis had antibodies against NMDAR that might be relevant to their illness, but did not differ from patients without NMDAR antibodies in clinical characteristics. Our study suggests that the only way to detect patients with these potentially pathogenic antibodies is to screen all patients with first-episode psychosis at first presentation.

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More information

Accepted/In Press date: 24 October 2016
e-pub ahead of print date: 8 December 2016
Published date: 27 January 2017

Identifiers

Local EPrints ID: 420428
URI: http://eprints.soton.ac.uk/id/eprint/420428
ISSN: 2215-0366
PURE UUID: 8b68c907-3ede-4f7e-bf30-aff9f6898e70
ORCID for Emma C. Palmer-Cooper: ORCID iD orcid.org/0000-0002-5416-1518

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Date deposited: 08 May 2018 16:30
Last modified: 16 Mar 2024 04:36

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Contributors

Author: Belinda R. Lennox
Author: Thomas Pollak
Author: Jane Hainsworth
Author: Jacqui Marks
Author: Leslie Jacobson
Author: Bethan Lang
Author: Hannah Fox
Author: Berne Ferry
Author: Linda Scoriels
Author: Hannah Crowley
Author: Peter B. Jones
Author: Paul J. Harrison
Author: Angela Vincent
Corporate Author: PPiP study team

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