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High levels of Anti-GAD65 and Anti-Ro52 autoantibodies in a patient with major depressive disorder showing psychomotor disturbance

https://doi.org/10.1016/j.jneuroim.2010.02.015Get rights and content

Abstract

Autoimmune disease and/or autoantibodies have been reported in mood disorder patients. We screened for autoantibodies to glutamic acid decarboxylase (GAD65), thyroid peroxidase (TPO), gastric H+/K+ ATPase (ATP4B), and Ro52 in a psychiatric patient cohort. A 24-year-old woman with major depressive disorder (MDD) with reduced psychomotor activity was identified with unusually high serum GAD65 and Ro52 autoantibody titers. Anti-GAD65 and anti-Ro52 autoantibodies were also elevated in the CSF from this patient. Longitudinal examination revealed a four-fold increase in anti-GAD65 serum antibody titers which correlated with exacerbation of psychomotor symptomatology. These results suggest the possibility that CNS autoimmunity may be responsible for the psychomotor impairment in this MDD patient.

Introduction

The relationship between the immune system and the pathogenesis of mood disorder has been the focus of numerous studies. Several groups observed an increased prevalence of autoimmune disease and/or autoantibodies in patients with bipolar disorder, including autoimmune thyroiditis and autoimmune atrophic gastritis (Kupka et al., 2002). Padmos et al. (2004) reported significant titers of autoantibodies to glutamic acid decarboxylase-65 (GAD65), thyroid peroxidase (TPO) and gastric H+/K+ ATPase (ATP4B) in a bipolar patient cohort. Luciferase Immunoprecipitation Systems (LIPS) is a highly sensitive and specific assay which harnesses light-emitting recombinant antigen fusion proteins to quantitatively measure patient antibody titers (Burbelo et al., 2009a). Previously, LIPS has been shown to be as good as, or superior to existing immunoassays in the detection of antibodies in several autoimmune conditions, including Sjögren's Syndrome (Burbelo et al., 2009b), type I diabetes (Burbelo et al., 2010) and Stiff Person Syndrome (SPS) (Burbelo et al., 2008a). For detection of anti-GAD65 autoantibodies, LIPS demonstrated equal diagnostic performance to the established radiobinding assay for the diagnosis of type I diabetes (Burbelo et al., 2010). Using LIPS, we screened a cohort of 58 psychiatric patients and 44 healthy controls for autoantibodies to TPO, ATP4B, Ro52 and GAD65.

Section snippets

Patient sera and CSF

Patients were evaluated under Institutional Review Board-approved protocols at the National Institute of Mental Health (Bethesda, MD), were medically healthy and had been unmedicated for at least three weeks prior to blood sampling. The cohort included 42 major depressive disorder patients (21 currently-depressed and 21 in full remission; DSM-IV criteria), 16 depressed bipolar disorder patients, and 44 healthy controls. The controls were recruited from the same community as the patients using

Results

The LIPS assay format was used to screen a cohort of mood disorder patients and controls for autoantibodies to several targets including TPO, Ro52 and GAD65. For each antigen tested, we used a cutoff based on the average plus five standard deviations of the healthy controls. None of the psychiatric patients showed autoantibody titers to TPO, a known thyroid autoantigen, above the established cutoff (data not shown). One MDD patient and one control were seropositive for ATP4B (data not shown).

Discussion

From screening a cohort of psychiatric patients for autoantibodies, a female MDD patient with significant psychomotor disturbance showed high levels of anti-GAD65 in both serum and CSF. These autoantibodies increased over time and correlated with the observed increase in psychomotor slowing in the patient. The presence of anti-GAD65 autoantibodies in the patient's serum and CSF is consistent with studies detecting these autoantibodies in other neurological diseases with movement disorders

Acknowledgements

This research was supported by the Intramural Research Program of the National Institute of Dental and Craniofacial Research, the National Institutes of Health.

References (16)

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1

Current address: University of Utah, School of Medicine, 30 N 1900 E RM 5R210, Salt Lake City, UT 84112, United States.

2

Current address: University of Oklahoma School of Medicine, Laureate Institute for Brain Research, 6655 So. Yale Ave., Tulsa OK, 73019, United States.

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