Anti-N-methyl-D-aspartate receptor antibodies, cognitive dysfunction, and depression in systemic lupus erythematosus

Arthritis Rheum. 2006 Aug;54(8):2505-14. doi: 10.1002/art.22031.


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 > or =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.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Adult
  • Aged
  • Autoantibodies / blood
  • Autoantibodies / immunology
  • Brain / pathology
  • Cognition Disorders / diagnosis
  • Cognition Disorders / etiology
  • Cognition Disorders / immunology*
  • Depression / diagnosis
  • Depression / etiology
  • Depression / immunology*
  • Female
  • Humans
  • Lupus Erythematosus, Systemic / immunology*
  • Lupus Erythematosus, Systemic / physiopathology
  • Lupus Erythematosus, Systemic / psychology*
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Neuropsychological Tests
  • Receptors, N-Methyl-D-Aspartate / immunology*


  • Autoantibodies
  • Receptors, N-Methyl-D-Aspartate