Disease-relevant autoantibodies in first episode schizophrenia

Zandi, Michael S; Irani, Sarosh R.; Lang, Bethan; Waters, Patrick; Jones, Peter B.; McKenna, Peter J.; Coles, Alasdair; Vincent, Angela; Lennox, Belinda

doi:10.1007/s00415-010-5788-9

Cited by 282 publications

(288 citation statements)

References 14 publications

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“…This has resulted in a surge of interest in whether a sub-group of people with psychosis have serum antibodies to certain neuronal antigens, although the specificity, sensitivity and clinical relevance of these remain unclear (Coutinho et al, 2014, Deakin et al, 2014, Pollak et al, 2014. These auto-antibodies target synaptic or extrasynaptic membrane-expressed proteins, with greatest interest in antibodies to the N-Methyl-DAspartate receptor (NMDAR) and the voltage gated potassium channel (VGKC)-complex, which includes antigens leucine-rich glioma inactiviated-1(LGI1) and contactin-associated protein-2 (CASPR2) (Ezeoke et al, 2013, Pearlman and Najjar, 2014, Steiner et al, 2013, Zandi et al, 2011.…”

Section: Introductionmentioning

confidence: 99%

“…Those affected are classically older than those with NMDAR antibody encephalitis. VGKC-complex antibodies were identified in one patient out of 46 with FEP (Zandi et al, 2011).…”

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confidence: 99%

“…A prospective cohort study in first episode psychosis (FEP) identified serum NMDAR antibodies in 6.4% of patients (n=3/47) (Zandi et al, 2011) using a live cell-based assay (CBA) and wellestablished subjective visual scoring system (Irani et al, 2010b). A recent case-control study in FEP identified an increased prevalence of NMDAR antibodies (n=7/228; 3% of total population) compared to controls (n=0/105), with no difference in the prevalence of LGI1, CASPR2 or VGKC-complex antibodies between the groups (Lennox et al, 2017).…”

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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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Section: Introductionmentioning

confidence: 99%

“…Those affected are classically older than those with NMDAR antibody encephalitis. VGKC-complex antibodies were identified in one patient out of 46 with FEP (Zandi et al, 2011).…”

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

et al. 2017

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“…For various reasons, the production of anti-NMDAr antibodies is a plausible mechanism to explain at least a percentage of schizophrenic cases [149]: several studies reported that 5-10% of cases are associated with the presence of these antibodies in serum and cerebrospinal fluid [150,151,154]; kynurenic acid is an antagonist of glutamate via blockade of NMDA receptors, as commented in the previous section, suggesting that it contributes to the pathogenesis of schizophrenia [122]; persistent blockade of NMDA receptors in experimental animals recreates clinical characteristics of schizophrenia [155]; selective elimination of subunit GluN1 of the NMDA receptor in neurons of the cortex and hippocampus in early postnatal development contributes to the pathophysiology of schizophrenia-related disorders in mice [156]; some of the genes associated with schizophrenia are related to the NMDA receptor [157]; NMDA receptors are reduced in medication-free schizophrenic patients [158]; blockade of the receptor with ketamine or phencyclidine produces psychotic symptoms [159,160]; and de novo mutations (large chromosomal copy number changes) affect genes that encode one or more nucleotides among the glutamatergic postsynaptic proteins that form part of the receptor, providing insight into possible etiological mechanisms underlying schizophrenia [161].…”

Section: The N-methyl-d-aspartate Receptor Hypofunction Theory: Anti-mentioning

confidence: 99%

Toxoplasma gondii and Schizophrenia: A Relationship That Is Not Ruled Out

Sorlózano-Puerto¹,

Gutiérrez‐Fernández²

2016

Schizophrenia Treatment - The New Facets

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Over recent years, it has been proposed that some diseases of unknown origin, such as schizophrenia, may be caused by persistent chronic infections coupled with a genetic component and may be perpetuated by the immune system. This hypothesis is supported by epidemiological and biological evidence on the exposure of schizophrenics to infectious diseases during prenatal or postnatal periods, including Toxoplasma gondii, chlamydia, human herpes virus, human endogenous retroviruses, parvovirus B19, mumps, and flu viruses. This growing list of microbes will undoubtedly continue to increase in the future. Linking infection to schizophrenia is a complex challenge that requires further experimental and epidemiological research. T. gondii is the infectious agent that has most frequently been related to neuropsychiatric disorders, including schizophrenia, and it is considered to represent a highly useful model to analyze the influence of a microorganism on human behavior and the development of psychiatric disease. It may also help to detect patient subpopulations susceptible to treatment with specific antimicrobials by improving definition of the differential phenotype of the disease, and it offers the possibility of a preventive approach.

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“…Modified electroconvulsive therapy was effective for his psychiatric symptoms that were uncontrolled with medications due to their side effects (Ando et al, 2011). Recently, anti-NMDA receptor antibodies were detected in a small percentage of patients with a first episode of psychosis (Zandi et al, 2011), and in cases with a pure neuropsychiatric disorder (De Nayer, Myant, and Sindic, 2009). A good response to electroconvulsive therapy has been reported for anti-NMDA receptor encephalitis (Braakman et al, 2010).…”

Section: Psychiatric Symptomsmentioning

confidence: 99%

Clinical Aspects of Anti-NMDA Receptor Encephalitis

Shimazaki¹

2011

Pathogenesis of Encephalitis

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Disease-relevant autoantibodies in first episode schizophrenia

Cited by 282 publications

References 14 publications

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

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

Toxoplasma gondii and Schizophrenia: A Relationship That Is Not Ruled Out

Clinical Aspects of Anti-NMDA Receptor Encephalitis

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