N-methyl-D-aspartate receptor antibody and the choroid plexus in schizophrenia patients with tardive dyskinesia

Abstract

Background: Immune disturbance has been postulated to be one of the mechanisms underlying the pathogenesis of tardive dyskinesia (TD). Recently, the role of autoimmune abnormality in TD has been increasingly recognized. Autoantibodies against neuronal N-methyl-D-aspartate receptor (NMDAR) may be cross-reactive in the brain in neuropsychiatric disorders, and the choroid plexus (CP) is a crucial immune barrier in the central nervous system (CNS). We supposed that NMDAR antibodies might underlie the pathophysiological process of TD through the mediation of CP.

Methods: Serum NMDAR antibody levels were assessed by enzyme-linked immunosorbent assay, CP and ventricle volumes were assessed by magnetic resonance imaging in schizophrenia patients with TD (n = 61), without TD (NTD, n = 61), and in healthy controls (n = 74). Psychopathology and TD severity were assessed by the Positive and Negative Syndrome Scale and Abnormal Involuntary Movement Scale (AIMS).

Results: NMDAR antibody levels were significantly higher, CP volumes were larger in the TD group than in the NTD group (p = 0.022; p = 0.019, respectively). In the TD group, higher NMDAR antibody level was correlated with larger CP volume (β = 0.406, p = 0.002). An elevated NMDAR antibody level and enlarged CP volume were correlated with orofacial AIMS score (β = 0.331, p = 0.011; β = 0.459, p = 3.34 × 10^-4, respectively). In a mediation model, the effect of NMDAR antibody level on the orofacial AIMS score was mediated by the CP volume (indirect effect: β = 0.08, 95% confidence interval = 0.002-0.225; direct effect: β = 0.14, p = 0.154).

Conclusions: Our findings highlight a potential NMDAR antibody-associated mechanism in orofacial TD, which may be mediated by increased CP volume.

Keywords: Choroid plexus; NMDAR antibody; Tardive dyskinesia; Ventricle.