Antibodies to the glutamate receptor in Mania

Background: There is evidence that the glutamatergic system is involved in the pathophysiology of mania. Antibodies to the NR2 subunits of the N-methyl-D-aspartate (NMDA) receptor have been shown to adversely affect glutamate functioning. Methods: We measured serum antibodies to the NR2 peptide of the NMDA receptor in 60 individuals with different subtypes of mania, including schizoaffective cases, who were assessed at up to three time points. We also measured these antibodies in 295 individuals in other psychiatric groups and in 170 non-psychiatric controls. NR2 antibody levels were compared among groups by multivariate analyses and within the mania group by repeated measures analysis of variance. Results: Individuals with mania had increased levels of antibodies to the NR2 peptide compared to levels in non-psychiatric controls when measured at the time of admission (t=2.99, p=0.003) and the time of evaluation (t=2.57, p=0.010), but not at follow-up sixmonths later. The levels of antibodies in individuals in other psychiatric groups did not differ significantly from the levels measured in the control population. Within the mania group, there was a significant decrease in antibody levels over the three time points of the study (F=5.4, df=2, p=0.0067). Conclusions: NR2 antibodies are elevated during the acute phase of mania but not at follow-up. Our findings support a role for antibodies to the NMDA receptor in the pathogenesis of acute mania.