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

Abstract

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

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

“…Additionally, one study that screened for IgA and IgM antibodies was negative [27]. Finally, a few other studies that either screened for antibodies against the NR1a/NR2b receptor subunit [10, 31], NR2a/NR2b subunit [32], or non-specifically for both NR1 and NR2 subunits [33-36], have found seropositivity in a small percentage of patients. As only antibodies directed against the NR1 subunit are known to produce anti-NMDAR encephalitis, the clinical relevance of these findings remains unclear.…”

“…A number of studies that tested for IgG, IgA, or IgM anti-CASPR2 antibodies found seropositivity in a small percentage (2.5% or less) of patients [11, 15, 24, 29, 36], although numerous other studies were negative [16, 18, 20, 26, 28]. Of note, all of the positive studies that included a healthy control group, however, also found antibodies in a small number of controls (up to 2.9%), and no group differences were found [11, 15, 36].…”

“…Of note, all of the positive studies that included a healthy control group, however, also found antibodies in a small number of controls (up to 2.9%), and no group differences were found [11, 15, 36]. …”

“…Only three studies found anti-LGI1 antibodies in a small subset of schizophrenia spectrum disorder patients (2.0% or less) [11, 15, 36], whereas six studies were negative [16, 18, 20, 24, 26, 29]. All of the positive studies included a healthy control group for comparison, two of which found anti-LGI1 antibodies in a small number of healthy controls (2% and <0.1%, respectively), and no group differences were found [11, 36].…”

“…All of the positive studies included a healthy control group for comparison, two of which found anti-LGI1 antibodies in a small number of healthy controls (2% and <0.1%, respectively), and no group differences were found [11, 36]. …”