The Study Of Glutamate Receptor Antibody Levels In Treatment Resistant Schizophrenia

Introduction:About 1/3 of schizophrenic patients do not respond to antipsychotics,known as treatment resistant schizophrenia.Evidences have shown that both glutamatergic system dysfunction and immune system imbalance are involved in the pathophysiological process of treatment resistant schizophrenia,and autoantibodies to glutamate receptors may connect the two.Hence,this study measured four serum glutamate receptor antibody levels in patients with treatment resistant schizophrenia to support glutamatergic and neuroimmunological hypotheses.Method:This study included 37 treatment resistant schizophrenia patients on clozapine(TRS-C),39 treatment resistant schizophrenia patients not on clozapine(TRS-n C),and 35 non-treatment resistant schizophrenia patients(NTRS).Severity of clinical symptoms was evaluated with Positive and Negative Symptom Scale(PANSS).Cognitive function was assessed using the MATRICS Consensus Cognitive Battery(MCCB).Serum N-methyl-D-aspartate receptor(NMDAR)antibody concentrations were determined by enzyme linked immunosorbent assay(ELISA).Result:The concentrations of four glutamate receptor antibodies in TRS-n C were higher than those in NTRS(p < 0.001).The anti-m Glu R3 antibody levels in TRS-C were similar to those in NTRS group(p = 0.233),and the concentrations of the other three antibodies were between the other two groups.In all three groups,no significant association was found between antibody levels and symptom severity or cognitive function.Conclusion:The treatment resistance of schizophrenia was related to the various elevated serum glutamate receptor antibody levels.Clozapine treatment could reduce antibody levels and improve positive symptoms and some cognitive functions.Higher glutamate receptor antibody levels may contribute to the poor efficacy of existing antipsychotics,which may serve as a target for new drug development in the future.