Elsevier

Schizophrenia Research

Volume 190, December 2017, Pages 28-31
Schizophrenia Research

Seroprevalence survey of selective anti-neuronal autoantibodies in patients with first-episode schizophrenia and chronic schizophrenia

https://doi.org/10.1016/j.schres.2017.03.012Get rights and content

Abstract

Autoimmune encephalopathy caused by autoantibodies against neuronal cell-surface proteins in the brain is a newly discovered disease category associated with psychiatric disorders. Correct diagnosis of this condition relies on the detection of specific autoantibodies in the blood or cerebral spinal fluid in addition to the clinical presentations. The study aimed to understand the seroprevalence of selective anti-neuronal autoantibodies in our patients with schizophrenia. First, we screened for six anti-neuronal autoantibodies in an archived blood sample collected from patients with the first-episode schizophrenia. The six autoantibodies including antibodies against N-methyl-d-aspartate (NMDA) receptor, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors 1 and 2, γ-butyric acid receptor type B1 (GABARB1), leucine-rich glioma inactivated-1 (LGI1) protein, and contactin-associated protein-like 2 (CASPR2) protein. A total of 78 plasma samples (46 males and 32 females) were investigated; however, no positive case was identified. In this second study, we screened anti-NMDA receptor autoantibodies in a blood sample of 234 patients with chronic schizophrenia (133 females and 101 males) including 48 patients defined as treatment resistance. None of this sample was detected as positive. The negative findings in this study suggest that the seroprevalence of autoantibodies against neuronal surface proteins might be low in patients diagnosed with schizophrenia.

Introduction

Schizophrenia is a devastating chronic mental disorder that affects approximately 1% of the general population. It is also a complex disorder with high clinical and etiological heterogeneity. Immune system dysfunction is an important factor associated with the pathogenesis of schizophrenia. Several epidemiological studies have demonstrated that patients with autoimmune diseases had increased the risk of schizophrenia and other psychiatric diagnoses, and patients with schizophrenia had a higher prevalence of autoimmune diseases (Benros et al., 2014, Chen et al., 2012). Furthermore, increased prevalence of multiple autoantibodies was reported in a systematic and quantitative review of blood autoantibodies in schizophrenia (Ezeoke et al. 2013). Together, these data suggest autoimmune diseases are associated with the pathogenesis of schizophrenia and its related disorders.

Recently, several new autoantibodies against neuronal cell-surface proteins and synaptic proteins were detected in patients presenting with a range of acute neuropsychiatric features, representing a new type of autoimmune encephalitis associated with psychiatric disorders (Lancaster, 2016, Linnoila et al., 2014). The correct diagnosis of this condition relies on the serological tests to detect the autoantibodies against neuronal surface proteins, which are only available recently. We were interested to know whether some of our first-episode schizophrenia might be due to this condition. Hence, we conducted a serological screening of autoantibodies against six neuronal cell-surface proteins in a sample of archived plasma from 78 patients diagnosed with first-episode schizophrenia using a commercially available indirect immunofluorescence assay. The six autoantibodies including antibodies against N-methyl-d-aspartate (NMDA) receptor, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors 1 and 2, γ-butyric acid receptor type B1 (GABARB1), leucine-rich glioma inactivated-1 (LGI1) protein, and contactin-associated protein-like 2 (CASPR2) protein.

Among these autoimmune encephalopathies associated with psychiatric condition, anti-NMDA receptor encephalitis is the most well-studied in recent years. It is characterized by the presence of IgG antibody against the NR1 subunit of NMDA receptor in the affected patients. Several studies reported the detection of anti-NMDA receptor autoantibodies in patients with acute psychosis and schizophrenia-related diagnoses (Wandinger et al. 2011). The disease can occur in patients of all ages, and more predominantly in female patients. Patients with anti-NMDA receptor encephalitis usually have prodromal symptoms of a headache or fever, followed by the quick development of consciousness level change and a wide spectrum of psychiatric symptoms such as agitation, irritability, anxiety, insomnia, hallucinations, delusions, aggression, and bizarre behaviors. A wide range of neurological symptoms may concur with or follow the appearance of psychiatric symptoms, including movement abnormalities, autonomic dysregulation, seizure attacks, and loss of consciousness (Dalmau et al., 2011, Leypoldt et al., 2015). It is suggested that anti-NMDA receptor encephalitis should be considered as an important differential diagnosis of patients with a primary psychiatric diagnosis (Barry et al., 2015, Barry et al., 2011, Chapman and Vause, 2011). Early recognition of this condition and timely treatment with immunotherapy will have a better outcome and even recovery in affected patients (Titulaer et al. 2013).

We were interested to know whether some of the patients diagnosed with chronic schizophrenia or even those who were refractory to psychopharmacotherapy might be associated with anti-NMDA receptor encephalopathy. Hence, in the second study, we conducted a seroprevalence survey of anti-NMDA receptor autoantibodies in patients with chronic schizophrenia, including some who were refractory to antipsychotic treatment.

Section snippets

Subjects

For the first-episode schizophrenia study, the patients came from two research projects of the early course of schizophrenia (Liu et al., 2013, Liu et al., 2011). Both projects have been approved by the institutional review board of the study hospital. All adult participants voluntarily provided their written informed consents and minors gave written assent with informed consent from their parents after full explanation of the study procedures to them. We recruited the patients between 16 and 45

Results

In the first-episode schizophrenia study, none of the 78 patients was positive in the screening of six neuronal autoantibodies using the indirect immunofluorescent cell-based assay. In the chronic schizophrenia study, also no positive case among 234 patients was detected in the survey of anti-NMDA receptor autoantibody. Two patients with ambiguous results in the initial screening were subjected to further verification test using rat brain immunohistochemistry assay; however, both of them were

Discussion

In the first study, we screened for autoantibodies against six neuronal cell-surface proteins in a sample of archived plasmas from 78 patients with first-episode schizophrenia and found no positive case in this sample. Similar study had been performed by Haussleiter and colleagues. They screened for the same six anti-neuronal autoantibodies as ours in 50 chronic patients with psychotic disorders of varying severity. No positive case was detected in their sample (Haussleiter et al. 2012).

Concluding remarks

In this study, we did not detect autoantibodies against six neuronal cell-surface proteins in a sample of seventy-eight patients with first-episode schizophrenia, nor did we detect anti-NMDA receptor autoantibodies in a sample of 234 patients with schizophrenia. Our data indicate that the seroprevalence of neuronal antibodies among schizophrenia patients might be low. However, autoimmune encephalopathy is still considered as a new emerging condition associated with psychiatric symptoms that are

Conflict of interest

The authors declare no conflict of interest.

Contributors

Chia-Hsiang Chen designed and conducted the study. Chih-Min Liu, Chen-Chung Liu, and Hai-Gwo Hwu recruited and evaluated the first-episode schizophrenia patients. Min-Chih Cheng, Ko-Huan Lin and Chia-Hsiang Chen helped recruit chronic schizophrenia patients and conducted the experiments. Chia-Hsiang Chen wrote the manuscript and all the authors reviewed and approved the manuscript.

Role of the funding source

The funding source has no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.

Acknowledgements

The study was supported by grants CMRPG3C1771, CMRPG3C1772, CMRPG3E0631, CMRPG3E0632 and CMRPG3E0633 from Chang Gung Memorial Hospital, Likou, Taoyuan, Taiwan. We also thank Mr. Synn-Yu Wu and Mr. Chun-Long Cheng for their technical assistance in carrying out the experimental works.

References (37)

Cited by (25)

  • The validity of atypical psychosis diagnostic criteria to detect anti-NMDA receptor encephalitis with psychiatric symptoms

    2022, Schizophrenia Research
    Citation Excerpt :

    The previously reported positive rate in CSF was 1.7 % (2/121) (Steiner et al., 2013), and in this study it was 3.3 % (5/151). Only two previous studies reported anti-NMDAR IgG antibodies in serum of patients with mood disorder, and the rates were 0 % (Steiner et al., 2013) and 3.4 % (Chen et al., 2017). Previous studies of anti-NMDAR IgG antibodies in patients with epilepsy did not mention psychiatric symptoms.

  • 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

    2021, The Lancet Psychiatry
    Citation Excerpt :

    Age data were reported for 11 samples, and sex or gender data were reported for 12 samples; of those with available data, all included adult patients (mean age 33·6 years [SD 8·3]; mean age range 24·1–46·1 years) and both males and females (mean percentage male 59% [SD 18%]; range 34–85%). Diagnoses included psychosis,7,10,16,18,28–30,33,34 schizophrenia,5,6,17,31,32 schizoaffective disorder,6,17 and schizophreniform disorder;5,6 details of illness phase and stage were not reported in a substantial number of studies (table 1).5–7,16,18,29,31,32 Total NOS scores ranged from 1 to 10 (mean 5·6 [SD 2·5]; table 1; appendix pp 5–6).

View all citing articles on Scopus
View full text