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 ≥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.