Absence ofN-Methyl-_D-Aspartate Receptor IgG Autoantibodies in Schizophrenia

Abstract

Patients with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis usually develop characteristic neurologic and psychiatric symptoms. Some patients have isolated psychiatric symptoms, mimicking a schizophrenia-like psychotic episode. 1,2 Therefore, it has been hypothesized that a subgroup of patients diagnosed as having schizophrenia actually has anti-NMDAR encephalitis, 2 which would have important clinical implications. Anti-NMDAR encephalitis is caused by IgG-type autoantibodies to the GluN1 subunit of the NMDAR. Conflicting reports have been published regarding the seroprevalence of anti-NMDAR autoantibodies in schizophrenia, ranging from 0% to 8%. 2,3 Some studies that reported high seroprevalences included patients with schizophrenia with atypical features, such as seizures and movement disorders. We hypothesized that the use of a single antibody detection assay, without any further validation of the findings, may have contributed to the inconsistent findings. 3 Here, we investigated the presence of anti-GluN1 IgG autoantibodies in 475 patients with a schizophrenia spectrum disorder and included the cross-validation of positive samples. Methods | The current study included 3 cohorts. Cohort 1 involved 415 patients with schizophrenia who were screened over 2 years with a full laboratory screening for studying meta

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

“…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]. Two negative studies, including one previously referenced study that also used the commercial CBA kit for testing some of its sample, used in-house CBAs [22, 23].…”

“…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]. Two negative studies, including one previously referenced study that also used the commercial CBA kit for testing some of its sample, used in-house CBAs [22, 23]. Similarly, consideration of the antibody detection method used in only those positive studies that included a healthy control group for comparison is mostly unrevealing.…”

The Clinical Challenge of Autoimmune Psychosis: Learning from Anti-NMDA Receptor Autoantibodies

“…The question is now in front of which clinical history or symptoms should we search for autoimmunity (53). The literature is still heterogeneous in the field and some have found no differences between patients (17, 20, 23). However, based on a French cohort of patients with psychiatric symptoms and autoantibodies against NMDA-R, we described clinical characteristics of patients that should lead to search of biological markers of an autoimmune psychosis [for details, see Ref.…”

Autoantibodies in Neuropsychiatric Disorders

“…Nevertheless, the results are controversial, since a number of other studies did not find autoantibodies in neuropsychiatric cohorts [146,159,162,163] or not specific to the disease [45,122]. New and more objective techniques, like flow cytometry CBA, are being introduced to the research routine [129,160], but a standardized procedure to screen patients for neuronal surface antigens needs to be defined to reduce results variability.…”

“…Nevertheless, these methods are still relatively new with room for improvement. Adequate training is necessary to interpret the results and to avoid false conclusions as they have been reported before [163,208]. The IHC is limited by high background with serum stainings.…”