Influence of methodological and patient factors on serum NMDAR IgG antibody detection in psychotic disorders: a meta-analysis of cross-sectional and case-control studies

Abstract

Background: Antibodies targeting the N-methyl-D-aspartate receptor (NMDAR) have been detected in psychosis patients. However, studies measuring the IgG subclass in serum have provided variable estimates of prevalence, and it is unclear whether these antibodies are more common in patients than controls. As these inconsistencies may be driven by methodological approaches and patient characteristics, we aimed to investigate the effect of these factors on heterogeneity.
Methods: We searched Web of Science and Ovid (Medline and PsycINFO) for cross-sectional and case-control studies published between January 2000 and May 2019 reporting NMDAR IgG antibody seropositivity in psychosis patients. Pooled proportions and odds ratios (OR) were derived using random-effects models. Meta-regression was used to investigate the effect of study factors on heterogeneity. Our protocol was registered on PROSPERO (CRD42018099874).
Findings: NMDAR IgG antibodies were detected in 0·73% (95% CI 0·09%–1·38%, I2=56%) of patients with psychosis in cross-sectional studies (N=14); however, case-control studies (N=14) showed that psychosis patients were not significantly more likely to be seropositive than healthy individuals (OR 1·58, 95% CI 0·78-3.17, I2=15%). Meta-regression analyses indicated significant effects of assay type, illness stage, and study quality/risk of bias on heterogeneity (p < 0.05 for all). Compared to those using a fixed cell-based assay, cross-sectional and case-control studies using the live method yielded higher pooled prevalence estimates (0·36% vs. 2·97%) and ORs (0·65 vs 4·43), respectively, in cross-sectional studies only, the prevalence was higher in exclusively first-episode samples (2·18% vs. 0·16%), and in case-control studies, higher ORs were reported in low quality studies (3·81 vs. 0·72).
Interpretation: Higher estimates of NMDAR IgG antibody prevalence are obtained with the live cell-based assay, and studies using this method find seropositivity is more common in patients than controls. Effects of illness stage and study quality/risk of bias on heterogeneity were not consistent across study designs, and we provide clear recommendations for clinicians and researchers regarding interpreting these findings.

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Identifiers

ORCID for Emma Palmer-Cooper: orcid.org/0000-0002-5416-1518

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