The putative functional rs1045881 marker of neurexin-1 in schizophrenia and clozapine response.

Neurexin-1 (NRXN1) modulates recruitment of NMDA receptors. Furthermore, clozapine reduces hyperactivity of NMDA receptors. Thus, regulation of the NRXN1 gene may mediate the efficacy of clozapine at reducing cortical hyperactivity. We examined the putative functional SNP, rs1045881, for association with schizophrenia, and the potential role of this SNP in clozapine response. The rs1045881 variant was not significantly associated with schizophrenia (N=302 case-control pairs), but with clozapine response (N=163; p=0.030). Baseline and BPRS scores after six months revealed a trend for rs1045881 genotype by treatment interaction (p=0.079). In the post hoc analysis, a significant association between BPRS negative symptoms score and genotype was observed (p=0.033). These results suggest that the rs1045881 NRXN1 polymorphism may influence clozapine response.