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 six months 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.
Sheppard Pratt The Stanley Neurovirology Laboratory, Department of Pediatrics, Johns Hopkins School of Medicine, Baltimore, MD, USA. fdickerson@sheppardpratt.org
Faith
F
Dickerson
Cassie
C
Stallings
Crystal
C
Vaughan
Andrea
A
Origoni
Sunil
S
Khushalani
Robert
R
Yolken
D000328:Adult; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D001714:Bipolar Disorder / Q000097:blood / Q000276:immunology*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011618:Psychotic Disorders / Q000097:blood / Q000276:immunology; D016194:Receptors, N-Methyl-D-Aspartate / Q000097:blood / Q000276:immunology*; D012559:Schizophrenia / Q000097:blood / Q000276:immunology
D001323:Autoantibodies; D007074:Immunoglobulin G; C120997:NR2A NMDA receptor; C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate