Anti-N-methyl-D-aspartate receptor antibodies, cognitive dysfunction, and depression in systemic lupus erythematosus.
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.
Lapteva
Larissa
L
Sjögren's Syndrome Clinic, National Institute of Dental and Craniofacial Research, NIH, Bethesda, Maryland 20892, USA. lapteva1@mail.nih.gov
Nowak
Miroslawa
M
Yarboro
Cheryl H
CH
Takada
Kazuki
K
Roebuck-Spencer
Tresa
T
Weickert
Thomas
T
Bleiberg
Joseph
J
Rosenstein
Donald
D
Pao
Maryland
M
Patronas
Nicholas
N
Steele
Sonya
S
Manzano
Melissa
M
van der Veen
Jan Willem C
JW
Lipsky
Peter E
PE
Marenco
Stefano
S
Wesley
Robert
R
Volpe
Bruce
B
Diamond
Betty
B
Illei
Gabor G
GG
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*
D001323:Autoantibodies; D016194:Receptors, N-Methyl-D-Aspartate