title: The putative functional rs1045881 marker of neurexin-1 in schizophrenia and clozapine response.
abstract: 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.
authors: Neurogenetics Section, Centre for Addiction and Mental Health, Toronto, Canada.
authors: Tristram A P
authors: TA
authors: Lett
authors: Arun K
authors: AK
authors: Tiwari
authors: Herbert Y
authors: HY
authors: Meltzer
authors: Jeffrey A
authors: JA
authors: Lieberman
authors: Steven G
authors: SG
authors: Potkin
authors: Aristotle N
authors: AN
authors: Voineskos
authors: James L
authors: JL
authors: Kennedy
authors: Daniel J
authors: DJ
authors: Müller
mesh_terms: D000704:Analysis of Variance; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D002135:Calcium-Binding Proteins; D016022:Case-Control Studies; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics*; D003024:Clozapine / Q000627:therapeutic use*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics*; D019006:Neural Cell Adhesion Molecules; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000188:drug therapy* / Q000235:genetics*; D013997:Time Factors; D044465:White People
chemical_list: D014150:Antipsychotic Agents; D002135:Calcium-Binding Proteins; D015816:Cell Adhesion Molecules, Neuronal; C539628:NRXN1 protein, human; D009419:Nerve Tissue Proteins; D019006:Neural Cell Adhesion Molecules; D003024:Clozapine