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Open Access 01-12-2016 | Research article

Prevalence of elevated serum anti-N-methyl-D-aspartate receptor antibody titers in patients presenting exclusively with psychiatric symptoms: a comparative follow-up study

Authors: Yoshihito Ando, Haruo Shimazaki, Katsutoshi Shiota, Syuichi Tetsuka, Koichi Nakao, Tatsuhiro Shimada, Kazumi Kurata, Jinichi Kuroda, Akihiro Yamashita, Hayato Sato, Mamoru Sato, Shinkichi Eto, Yasunori Onishi, Keiko Tanaka, Satoshi Kato

Published in: BMC Psychiatry | Issue 1/2016

Abstract

Background

Increasing numbers of patients with elevated anti-N-methyl-D-aspartate (NMDA) receptor antibody titers presenting exclusively with psychiatric symptoms have been reported. The aim of the present study was to clarify the prevalence of elevated serum anti-NMDA receptor antibody titers in patients with new-onset or acute exacerbations of psychiatric symptoms. In addition, the present study aimed to investigate the association between elevated anti-NMDA receptor titers and psychiatric symptoms.

Methods

The present collaborative study included 59 inpatients (23 male, 36 female) presenting with new-onset or exacerbations of schizophrenia-like symptoms at involved institutions from June 2012 to March 2014. Patient information was collected using questionnaires. Anti-NMDA receptor antibody titers were measured using NMDAR NR1 and NR2B co-transfected human embryonic kidney (HEK) 293 cells as an antigen (cell-based assay). Statistical analyses were performed for each questionnaire item.

Results

The mean age of participants was 42.0 ± 13.7 years. Six cases had elevated serum anti-NMDA antibody titers (10.2 %), four cases were first onset, and two cases with disease duration >10 years presented with third and fifth recurrences. No statistically significant difference in vital signs or major symptoms was observed between antibody-positive and antibody-negative groups. However, a trend toward an increased frequency of schizophrenia-like symptoms was observed in the antibody-positive group.

Conclusion

Serum anti-NMDA receptor antibody titers may be associated with psychiatric conditions. However, an association with specific psychiatric symptoms was not observed in the present study. Further studies are required to validate the utility of serum anti-NMDA receptor antibody titer measurements at the time of symptom onset.

Dalmau J, Tuzun E, Wu HY, Masjuan J, Rossi JE, Voloschin A, Baehring JM, Shimazaki H, Koide R, King D, et al. Paraneoplastic anti-N-methyl-D-aspartate receptor encephalitis associated with ovarian teratoma. Ann Neurol. 2007;61(1):25–36.CrossRefPubMedPubMedCentral

Dalmau J, Lancaster E, Martinez-Hernandez E, Rosenfeld MR, Balice-Gordon R. Clinical experience and laboratory investigations in patients with anti-NMDAR encephalitis. Lancet Neurol. 2011;10(1):63–74.CrossRefPubMedPubMedCentral

Abe M, Fukaya M, Yagi T, Mishina M, Watanabe M, Sakimura K. NMDA receptor GluRepsilon/NR2 subunits are essential for postsynaptic localization and protein stability of GluRzeta1/NR1 subunit. J Neurosci. 2004;24(33):7292–304.CrossRefPubMed

Rhoads J, Guirgis H, McKnight C, Duchemin AM. Lack of anti-NMDA receptor autoantibodies in the serum of subjects with schizophrenia. Schizophr Res. 2011;129(2-3):213–4.CrossRefPubMed

Haussleiter IS, Emons B, Schaub M, Borowski K, Brune M, Wandinger KP, Juckel G. Investigation of antibodies against synaptic proteins in a cross-sectional cohort of psychotic patients. Schizophr Res. 2012;140(1-3):258–9.CrossRefPubMed

Masdeu JC, Gonzalez-Pinto A, Matute C, Ruiz De Azua S, Palomino A, De Leon J, Berman KF, Dalmau J. Serum IgG antibodies against the NR1 subunit of the NMDA receptor not detected in schizophrenia. A J Psychiatry. 2012;169(10):1120–1.CrossRef

Zandi MS, Irani SR, Lang B, Waters P, Jones PB, McKenna P, Coles AJ, Vincent A, Lennox BR. Disease-relevant autoantibodies in first episode schizophrenia. J Neurol. 2011;258(4):686–8.CrossRefPubMed

Tsutsui K, Kanbayashi T, Tanaka K, Boku S, Ito W, Tokunaga J, Mori A, Hishikawa, Y, Shimizu T, Nishino S. Anti-NMDA-receptor antibody detected in encephalitis, schizophrenia, and narcolepsy with psychotic features. BMC psychiatry. 2012;12(1):37.CrossRefPubMedPubMedCentral

Steiner J, Walter M, Glanz W, Sarnyai Z, Bernstein HG, Vielhaber S, Kastner A, Skalej M, Jordan W, Schiltz K, et al. Increased prevalence of diverse N-methyl-D-aspartate glutamate receptor antibodies in patients with an initial diagnosis of schizophrenia: specific relevance of IgG NR1a antibodies for distinction from N-methyl-D-aspartate glutamate receptor encephalitis. JAMA Psychiatry. 2013;70(3):271–8.CrossRefPubMed

10.

Hammer C, Stepniak B, Schneider A, Papiol S, Tantra M, Begemann M, Siren AL, Pardo LA, Sperling S, Mohd Jofrry S, et al. Neuropsychiatric disease relevance of circulating anti-NMDA receptor autoantibodies depends on blood-brain barrier integrity. Mol Psychiatry. 2014;19(10):1143–9.CrossRefPubMed

11.

Steiner J, Teegen B, Schiltz K, Bernstein HG, Stoecker W, Bogerts B. Prevalence of N-methyl-D-aspartate receptor autoantibodies in the peripheral blood: healthy control samples revisited. JAMA Psychiatry. 2014;71(7):838–9.CrossRefPubMed

12.

Maneta E, Garcia G. Psychiatric manifestations of anti-NMDA receptor encephalitis: neurobiological underpinnings and differential diagnostic implications. Psychosomatics. 2014;55(1):37–44.CrossRefPubMed

13.

Gresa-Arribas N, Titulaer MJ, Torrents A, Aguilar E, McCracken L, Leypoldt F, Gleichman AJ, Balice-Gordon R, Rosenfeld MR, Lynch D, et al. Antibody titres at diagnosis and during follow-up of anti-NMDA receptor encephalitis: a retrospective study. Lancet Neurol. 2014;13(2):167–77.CrossRefPubMed

14.

Cheido MA, Idova GV. The differential contribution of dopamine D(1) and D (2) receptors to mu-opioidergic immunomodulation. Neurosci Behav Physiol. 2007;37(7):721–4.CrossRefPubMed

Title: Prevalence of elevated serum anti-N-methyl-D-aspartate receptor antibody titers in patients presenting exclusively with psychiatric symptoms: a comparative follow-up study
Authors: Yoshihito Ando
Haruo Shimazaki
Katsutoshi Shiota
Syuichi Tetsuka
Koichi Nakao
Tatsuhiro Shimada
Kazumi Kurata
Jinichi Kuroda
Akihiro Yamashita
Hayato Sato
Mamoru Sato
Shinkichi Eto
Yasunori Onishi
Keiko Tanaka
Satoshi Kato
Publication date: 01-12-2016
Publisher: BioMed Central
Published in: BMC Psychiatry / Issue 1/2016
Electronic ISSN: 1471-244X
DOI: https://doi.org/10.1186/s12888-016-0948-9

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Prevalence of elevated serum anti-N-methyl-D-aspartate receptor antibody titers in patients presenting exclusively with psychiatric symptoms: a comparative follow-up study

Abstract

Background

Methods

Results

Conclusion

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

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