Elsevier

Neuroscience Letters

Volume 534, 8 February 2013, Pages 217-222
Neuroscience Letters

Anti-glutamate receptor ɛ2 antibodies in psychiatric patients with anti-thyroid autoantibodies – A prevalence study in Japan

https://doi.org/10.1016/j.neulet.2012.10.060Get rights and content

Abstract

Patients with anti-thyroid antibodies (ATAs) present various kinds of psychiatric conditions. When these psychiatric patients with ATAs (PPATs) show responsiveness to immunotherapy, they are frequently diagnosed with a diffuse progressive type of Hashimoto's encephalopathy (HE). Anti-glutamate receptor ɛ2 subunit (GluRɛ2) antibodies have previously been reported in HE patients. However, it is unclear whether there is any relationship between PPATs, including HE patients, and anti-GluRɛ2 antibodies. We investigated anti-GluRɛ2 antibodies in the serum and cerebrospinal fluid (CSF) of 15 PPATs, and we compared the results with those of 11 patients with neuropsychiatric systemic lupus erythematosus (NPSLE), an anti-glutamate receptor antibody-related disease. We then compared the neuropsychiatric symptoms between the PPATs with and without anti-GluRɛ2 antibodies. The prevalence of anti-GluRɛ2 antibodies was significantly higher in the CSF than in the serum of PPATs (41.7% versus 6.7%; p = 0.040). The prevalence of anti-GluRɛ2 antibodies was slightly higher in the CSF of PPATs than NPSLE patients. PPAT-GluR(+)s showed a significantly higher prevalence of emotional instability (100% versus 33.3%; p = 0.03) and also showed a significantly lower prevalence of delusions (0% versus 100%; p = 0.001) and hallucinations (17% versus 83%; p = 0.038) than PPAT-GluR(−)s. Our results suggest that anti-GluRɛ2 antibodies may be associated with the neuropsychiatric manifestation of PPATs.

Highlights

► This is the first report on the prevalence of anti-GluRɛ2 antibodies in PPATs. ► Anti-GluRɛ2 antibodies were frequently observed in the CSF of PPATs. ► Anti-GluRɛ2 antibodies would relate to the neuropsychiatric manifestations of PPATs.

Introduction

A number of psychiatric disorders have been reported to have autoimmune factors in their etiologies [23]. Except for the possible effects of thyroid hormonal dysfunction, anti-thyroid antibodies (ATAs) have attracted interest because of their association with psychiatric disorders such as mood disorder [23], [32], anxiety disorder [4], schizophrenia [23], and dementia [10]. The ATAs were reported to be found in 9.2% of the admitted psychiatric inpatients. [16] When psychiatric patients with ATAs (PPATs) show responsiveness to immunotherapy, they are frequently diagnosed with a diffuse progressive type of Hashimoto's encephalopathy (HE) [5], [12], [21], [26]. The definition of HE is still unclear, as it involves some unknown autoimmune mechanisms, and the detailed prevalence of HE is still unknown. A diagnosis of HE is usually based on a combination of neuropsychiatric findings and the presence of ATAs and/or responsiveness to immunotherapy. Recently Shindo et al. [27] reported a case of HE with anti-glutamate receptor ɛ2 subunit (GluRɛ2) antibodies in the serum and cerebrospinal fluid (CSF). GluRɛ2 is a subunit of N-methyl-d-aspartate (NMDA) glutamate receptor, which is believed to play an important pathogenic role in schizophrenia and dementia [3], [6], [24].

Like HE, neuropsychiatric systemic lupus erythematosus (NPSLE) is a well-known autoimmune disease. The overall prevalence of neuropsychiatric feature of patients with SLE is varied widely between 37% and 95%. [17] Recently anti-NMDA receptor antibodies in the CSF of NPSLE patients have received particular attention because of their association with psychiatric symptoms [2], [9], [14], [22], [25], [34]. Among NPSLE patients, the relatively high prevalence of anti-NMDA receptor antibodies in the CSF was reported by Fragoso-Loyo et al. [14] and Arinuma et al. [2] and those were 35% and 69.6%, respectively. Anti-NMDA receptor antibodies in the CSF are believed to represent an important mechanism of cerebral dysfunction in NPSLE. However, it is unclear whether there is any relationship between PPATs, including HE patients, and anti-GluRɛ2 antibodies.

The purpose of the present study was to clarify the prevalence of anti-GluRɛ2 antibodies in PPATs. We compared the findings with a control group of patients with NPSLE, an anti-glutamate receptor antibody-associated disease. Additionally, we compared psychiatric features between PPATs with and without anti-GluRɛ2 antibodies.

Section snippets

Patients

We evaluated 15 PPATs and 11 NPSLE patients who had been tested for serum and/or CSF anti-GluRɛ2 antibodies between 2006 and 2011 at Yokohama City University Hospital, Yokohama, Japan. In these cases, some organic psychiatric or autoimmune disease, such as HE or NPSLE, was suspected because of the atypical course of their psychiatric symptoms and/or cognitive dysfunctions, and resistance to psychotropic agents.

All the PPATs visited the Department of Psychiatry at our hospital for treatment of

Patients and autoantibodies

The clinical profiles of the PPATs and NPSLE patients are shown in Table 1, Table 2, and the demographics are shown in Table 3.

Anti-GluRɛ2 antibodies

The prevalence of anti-GluRɛ2 antibodies is summarized in Table 3.

The prevalence of anti-GluRɛ2 antibodies was significantly higher in the CSF than in the serum of the PPATs (5/12 = 41.7% versus 1/15 = 6.7%; p = 0.040). The prevalence of anti-GluRɛ2 antibodies in the serum of the PPATs was significantly lower than in the serum of the NPSLE patients (1/15 = 6.7% versus 5/11 = 

Discussion

The present study is based on small number of cases but is the first report on the prevalence of anti-GluRɛ2 antibodies in PPATs. The prevalence of anti-GluRɛ2 antibodies was found to be slightly higher in the CSF of PPATs than in the CSF of NPSLE patients. This suggests that there is some relationship between anti-GluRɛ2 antibodies and PPATs, as in NPSLE.

De Giorgio et al. [9] reported that anti-DNA antibodies, which are pathologically important in SLE, cross-react with the NMDA receptor

Disclosure statement

None.

References (34)

  • M.G. Carta et al.

    The link between thyroid autoimmunity (antithyroid peroxidase autoantibodies) with anxiety and mood disorders in the community: a field of interest for public health in the future

    BMC Psychiatry

    (2004)
  • P. Castillo et al.

    Steroid-responsive encephalopathy associated with autoimmune thyroiditis

    Archives of Neurology

    (2006)
  • J.T. Coyle et al.

    Converging evidence of NMDA receptor hypofunction in the pathophysiology of schizophrenia

    Annals of The New York Academy of Sciences

    (2003)
  • J. Dalmau et al.

    Paraneoplastic anti-N-methyl-d-aspartate receptor encephalitis associated with ovarian teratoma

    Annals of Neurology

    (2007)
  • L.A. DeGiorgio et al.

    A subset of lupus anti-DNA antibodies cross-reacts with the NR2 glutamate receptor in systemic lupus erythematosus

    Nature Medicine

    (2001)
  • N. Döbert et al.

    Subclinical hyperthyroidism in dementia and correlation of the metabolic index in FDG-PET

    Acta Medica Austriaca

    (2003)
  • B.J. Emmer et al.

    Selective involvement of the amygdala in systemic lupus erythematosus

    PLoS Medicine

    (2006)
  • Cited by (0)

    View full text