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Research Article
Anti–N-methyl-D-aspartate receptor antibodies, cognitive dysfunction, and depression in systemic lupus erythematosus
Article first published online: 25 JUL 2006
DOI: 10.1002/art.22031
Copyright © 2006 by the American College of Rheumatology
1529-0131/asset/cover.gif?v=1&s=104d5c2bb8ef72deba26790b855af7ab80697a0e "Arthritis & Rheumatism")
Additional Information
How to Cite
Lapteva, L., Nowak, M., Yarboro, C. H., Takada, K., Roebuck-Spencer, T., Weickert, T., Bleiberg, J., Rosenstein, D., Pao, M., Patronas, N., Steele, S., Manzano, M., van der Veen, J. W. C., Lipsky, P. E., Marenco, S., Wesley, R., Volpe, B., Diamond, B. and Illei, G. G. (2006), Anti–N-methyl-D-aspartate receptor antibodies, cognitive dysfunction, and depression in systemic lupus erythematosus. Arthritis & Rheumatism, 54: 2505–2514. doi: 10.1002/art.22031
Publication History
- Issue published online: 25 JUL 2006
- Article first published online: 25 JUL 2006
- Manuscript Accepted: 8 MAY 2006
- Manuscript Received: 27 JUL 2005
Funded by
- Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH
- Abstract
- Article
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- Cited By
Abstract
Objective
To assess the association of cognitive dysfunction and depression with serum antibodies to N-methyl-D-aspartate (NMDA) receptor (anti-NR2) and analyze clinical and neuroimaging correlates in patients with systemic lupus erythematosus (SLE).
Methods
Sixty patients underwent neurocognitive assessment, evaluation for depression with the Beck Depression Inventory II (BDI-II) and psychiatric interview (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition [DSM-IV] criteria), brain magnetic resonance imaging, and proton magnetic resonance spectroscopy imaging (1H-MRSI). Cognition was assessed in 5 domains: memory, attention/executive, visuospatial, motor, and psychomotor, and adjusted to each individual's best level of prior cognitive functioning estimated from the reading subtest of the Wide Range Achievement Test–3 (WRAT-3). Serum anti-NR2 antibodies were measured by enzyme-linked immunosorbent assay using a pentapeptide from the human NMDA receptor.
Results
Cognitive dysfunction was found in 28 of 60 patients (mild in 8, moderate in 20) before adjustment for WRAT-3 and in 35 of 60 patients (mild in 15, moderate in 11, and severe in 9) after adjustment for WRAT-3. The changes were most pronounced in the memory and visuospatial domains. There was no significant association between anti-NR2 antibody levels and cognition. On 1H-MRSI, patients with moderate or severe cognitive dysfunction had significantly higher choline:creatine ratios in the dorsolateral prefrontal cortex and the white matter, compared with patients with mild or absent cognitive dysfunction. Anti-NR2 antibodies were significantly correlated with BDI scores; patients with BDI-II scores of ≥14 had higher serum levels of anti-NR2 antibodies (P = 0.005, 95% confidence interval 0.83, 4.31), and there was a trend toward higher anti-NR2 antibody levels among patients who fulfilled the DSM-IV criteria for major depression.
Conclusion
Serum anti-NR2 antibodies are associated with depressive mood but not with cognitive dysfunction in SLE at a given time point. Larger longitudinal studies are needed to address the possible association between anti-NR2 antibodies and depression in SLE.