Multiple serum anti-glutamate receptor antibody levels in clozapine-treated/naïve patients with treatment resistant schizophrenia

Abstract Background Glutamatergic function deficits have been associated with the pathogenesis of treatment resistant schizophrenia (TRS), while the effects of clozapine on the glutamate system may contribute to its superior efficacy. In recent years, evidence emerged supporting the involvement of immune processes and increased prevalence of antineuronal antibodies in TRS. In this present study, we aimed to investigate multiple anti-glutamate receptor antibody levels in TRS and explored the effects of clozapine on these antibody levels. Methods We measured and compared multiple anti-glutamate receptor (NMDAR, AMPAR, mGlur3, mGluR5) antibody levels among clozapine-treated patients with TRS (TRS-C, n = 37), clozapine-naïve patients with TRS (TRS-nC, n = 39), and patients with nTRS (NTRS, n = 35), using enzyme linked immunosorbent assay (ELISA). Severity of clinical symptoms was evaluated with Positive and Negative Symptom Scale (PANSS). Cognitive function was assessed using the MATRICS Consensus Cognitive Battery (MCCB). Results The four glutamate receptor antibody levels in the TRS-nC were higher than those in the NTRS (p < 0.001). The anti-mGluR3 antibody levels in the TRS-C were similar to those in the NTRS (p = 0.233), and the other three antibody levels were between the NTRS and the TRS-nC. However, in all three groups, no significant associations were found between antibody levels and symptom severity or cognitive function. Conclusions Our findings suggest that both glutamatergic function deficits and immune processes may play a role in the pathogenesis of TRS. The effect of clozapine targeting anti-glutamate receptor antibody levels may be an element of its pharmacology that contribute to its therapeutic effects.