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

Lennox, Belinda; Palmer-Cooper, Emma; Pollak, Thomas A; Hainsworth, Jane; Marks, Jacqueline; Jacobson, Leslie; Lang, Bethan; Fox, Hannah; Ferry, Berne; Scoriels, Linda; Crowley, Hannah; Jones, Peter B.; Harrison, Paul J.; Vincent, Angela

doi:10.1016/s2215-0366(16)30375-3

Cited by 160 publications

(166 citation statements)

References 33 publications

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“…The frequency of antibody positivity was around 5% or less in all but one study [13] and was less than 1% in two studies [11, 12]. Of the studies that produced positive results, five included a healthy control group for comparison [10-13, 15], and two of these studies, in addition to further testing in one of them, also identified antibodies in 0.4–1.2% of healthy controls [11, 12, 30], making interpretation of the results difficult. No group differences in seroprevalence were found, where reported.…”

Section: Resultsmentioning

confidence: 99%

“…Of the seven positive studies, four used a commercially available fixed cell-based assay (CBA) [10-12, 16], two used a live CBA [13, 15], and one used both, as well as a single molecule-based imaging method, for the sake of comparing approaches [14]. The majority of negative studies also used the same aforementioned commercially available CBA (or a modification of it) [17-22, 24-29], and four of these studies also included immunohistochemistry for further testing [19, 26-28].…”

Section: Resultsmentioning

confidence: 99%

“…Similarly, consideration of the antibody detection method used in only those positive studies that included a healthy control group for comparison is mostly unrevealing. Specifically, a fixed CBA was used in the two studies that found seropositivity among both healthy control and patient groups [11, 12], as well as in one of the three studies that only found seropositivity in the patient group but not in the control group [10]; the other two studies used live CBAs [13, 15]. However, it should be noted that the follow-up study to that by Steiner et al [10] did also find seropositivity in a small number of control participants using the same commercially available fixed CBA [30].…”

Section: Resultsmentioning

confidence: 99%

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Clinically Relevant Anti-Neuronal Cell Surface Antibodies in Schizophrenia Spectrum Disorders

Colijn

Ismail

2019

Neuropsychobiology

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Schizophrenia is a phenotypically heterogeneous and poorly understood disorder. While its etiology is likely multifactorial, immune system dysfunction has increasingly been implicated in its development. As hallucinations and delusions occur frequently and prominently in autoimmune encephalitis (AE), numerous studies have sought to determine whether a small subset of individuals diagnosed with schizophrenia possess anti-neuronal antibodies implicated in AE. Exploring this possibility is of clinical relevance, as identifying individuals with AE who have been misdiagnosed as having a primary psychotic disorder may allow for the implementation of appropriate immune-related therapies as early as possible in the course of the illness, in order to optimize outcomes, reduce illness chronicity, and minimize adverse events. This qualitative review serves to provide an overview of the existing literature on this topic, as well as to update previously published reviews. Although there is some evidence to suggest that in rare cases AE may be misdiagnosed as a primary psychotic disorder, particularly early in the course of the illness, numerous methodological differences between studies likely account for the highly variable findings, and interpretation of the results is particularly limited by a paucity of cerebrospinal fluid data. Moreover, the prevalence of misdiagnosis in chronic and treatment-resistant populations remains understudied. This is particularly problematic, as treatment resistance may represent an enriched population with respect to the presence of anti-neuronal antibodies, and given that such patients have few evidence-based treatment options available to them beyond clozapine.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Clinically Relevant Anti-Neuronal Cell Surface Antibodies in Schizophrenia Spectrum Disorders

Colijn

Ismail

2019

Neuropsychobiology

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“…During the course of the study patients with organic presentations were excluded which may be one reason for the low proportion of positive results in comparison with Lennox et al 2017(Lennox et al, 2017. Further, as the proportion of cases and of controls with antibody positivity was small, it remains a possibility that the negative findings may be due to insufficient statistical power.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2017

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Abstract: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 2009-2011 as part of the Genetics and Psychosis(GAP)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.LGI1 and CASPR antibodies were also measured. Notably,patients with suspicion of organic disease were excluded. Results Powered by Editorial Manager® and ProduXion Manager® from Aries Systems CorporationVGKC-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. Powered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporation

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“…Moreover, there is growing evidence that common psychiatric illnesses such a schizophrenia may be driven by an underlying antibody-mediated encephalitis, further softening the boundary between psychiatry and neurology. 10 In their case study Newrick et al 11 discuss the 'patient with psychotic depression languishing on a neurology ward for want of reasonably dosed antipsychotics'. Our patient reminds us of the 'encephalitic patient languishing on a psychiatric unit for want of i m m u n o s u p p r e s s i o n ' .…”

Section: Discussionmentioning

confidence: 99%

Limbic encephalitis and bipolar affective disorder: a slow awakening

Lilford¹,

Morrison²,

Morgan³

et al. 2018

Prog Neurol Psychiatry

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There is increasing evidence for the role of autoimmune encephalitis in the aetiology of psychosis. Here, Dr Lilford and colleagues describe the case of a 74‐year‐old lady who presented as hypomanic almost a year previously and then developed bizarre stereotyped movements, periods of absences and became confused. She was admitted to an old age psychiatric ward and was then subsequently diagnosed with non‐paraneoplastic limbic encephalitis with high levels of voltage‐gated potassium channel complex antibodies. The authors discuss her treatment with immunosuppressive drugs, which resulted in significant clinical improvement.

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

Abstract: Medical Research Council.

Cited by 160 publications

References 33 publications

Clinically Relevant Anti-Neuronal Cell Surface Antibodies in Schizophrenia Spectrum Disorders

Clinically Relevant Anti-Neuronal Cell Surface Antibodies in Schizophrenia Spectrum Disorders

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

Limbic encephalitis and bipolar affective disorder: a slow awakening

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