title: Schizophrenia severity and clozapine treatment outcome association with oxytocinergic genes.
abstract: Antipsychotic drugs are the best means available for symptomatically treating individuals suffering from schizophrenia; however, there is a significant variability in clinical response to these psychotropic medications. Previous findings connect oxytocin (OXT) with schizophrenia and antipsychotic action. Therefore, we evaluated if OXT and OXT receptor (OXTR) genes might play a role in the symptom severity and clozapine treatment response in schizophrenia subjects. The rs2740204 variant in the OXT gene was significantly associated with treatment response (after 1000 permutations p=0.042) and nominally associated with negative symptoms in our sample. Furthermore, variants in the OXTR were nominally associated with severity of overall symptoms accessed using the Brief Psychiatric Rating Scale (rs237885, rs237887) as well as on the improvement of the positive symptoms (rs11706648, rs4686301, rs237899). Additional association studies in independent samples will be able evaluate whether OXT and OXTR genes are truly playing a role in the clozapine treatment outcome.
authors.affiliation: Neurogenetics Section, Centre for Addiction and Mental Health, Toronto, ON, Canada.
authors.forename: Renan P
authors.initials: RP
authors.lastname: Souza
authors.forename: Vincenzo
authors.initials: V
authors.lastname: de Luca
authors.forename: Herbert Y
authors.initials: HY
authors.lastname: Meltzer
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Lieberman
authors.forename: James L
authors.initials: JL
authors.lastname: Kennedy
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D003024:Clozapine / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D010121:Oxytocin / Q000235:genetics*; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011569:Psychiatric Status Rating Scales; D018045:Receptors, Oxytocin / Q000235:genetics*; D012559:Schizophrenia / Q000188:drug therapy* / Q000235:genetics*; D013223:Statistics as Topic; D016896:Treatment Outcome
chemical_list: D014150:Antipsychotic Agents; D018045:Receptors, Oxytocin; D010121:Oxytocin; D003024:Clozapine