Pathogenicity of Antibodies against NMDA Receptor: Molecular Insights into Autoimmune Psychosis

Recent years have seen a flourishing literature on detection of circulating autoantibodies against neurotransmitter receptors in patients with neuropsychiatric disorders. These studies have generated hope for a better understanding of the underlying molecular dysfunctions and for appropriate therapeutic strategies. However, the detection of these autoantibodies in healthy subjects, and the lack of mechanistic insights have fostered debate about the pathogenic role of such autoantibodies. Here, we specifically discuss the biological evidence linking autoantibodies directed against the glutamatergic N-methyl-d-aspartate (NMDA) receptor (NMDAR-Abs) and psychosis, emphasising recent single-molecule imaging investigations that unveiled the impaired surface trafficking of NMDAR in the presence of NMDAR-Abs from psychotic patients. Although still in its infancy, the hypothesis that NMDAR-Abs from patients with psychosis play a pathogenic role is thus gaining support, opening avenues of fundamental and translational investigations.