title: Anti-N-methyl-D-aspartate receptor antibodies, cognitive dysfunction, and depression in systemic lupus erythematosus.
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 > 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Sjögren's Syndrome Clinic, National Institute of Dental and Craniofacial Research, NIH, Bethesda, Maryland 20892, USA. lapteva1@mail.nih.gov
authors.forename: Larissa
authors.initials: L
authors.lastname: Lapteva
authors.forename: Miroslawa
authors.initials: M
authors.lastname: Nowak
authors.forename: Cheryl H
authors.initials: CH
authors.lastname: Yarboro
authors.forename: Kazuki
authors.initials: K
authors.lastname: Takada
authors.forename: Tresa
authors.initials: T
authors.lastname: Roebuck-Spencer
authors.forename: Thomas
authors.initials: T
authors.lastname: Weickert
authors.forename: Joseph
authors.initials: J
authors.lastname: Bleiberg
authors.forename: Donald
authors.initials: D
authors.lastname: Rosenstein
authors.forename: Maryland
authors.initials: M
authors.lastname: Pao
authors.forename: Nicholas
authors.initials: N
authors.lastname: Patronas
authors.forename: Sonya
authors.initials: S
authors.lastname: Steele
authors.forename: Melissa
authors.initials: M
authors.lastname: Manzano
authors.forename: Jan Willem C
authors.initials: JW
authors.lastname: van der Veen
authors.forename: Peter E
authors.initials: PE
authors.lastname: Lipsky
authors.forename: Stefano
authors.initials: S
authors.lastname: Marenco
authors.forename: Robert
authors.initials: R
authors.lastname: Wesley
authors.forename: Bruce
authors.initials: B
authors.lastname: Volpe
authors.forename: Betty
authors.initials: B
authors.lastname: Diamond
authors.forename: Gabor G
authors.initials: GG
authors.lastname: Illei
mesh_terms: D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D001921:Brain / Q000473:pathology; D003072:Cognition Disorders / Q000175:diagnosis / Q000209:etiology / Q000276:immunology*; D003863:Depression / Q000175:diagnosis / Q000209:etiology / Q000276:immunology*; D005260:Female; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000503:physiopathology / Q000523:psychology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D016194:Receptors, N-Methyl-D-Aspartate / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D016194:Receptors, N-Methyl-D-Aspartate