OXTR polymorphisms associated with severity and treatment responses of schizophrenia.

Abstract

The mechanisms generating specific symptoms of schizophrenia remain unclear and genetic research makes it possible to explore these issues at a fundamental level. Taking into account the associations between the oxytocin system and social functions, which are apparently impaired in schizophrenia patients, we hypothesized that the oxytocin receptor gene (OXTR) might be associated with schizophrenia symptoms in both severity and responses to antipsychotics and did this exploratory positional study. A total of 2363 patients with schizophrenia (1181 males and 1182 females) included in our study were randomly allocated to seven antipsychotic treatment groups and received antipsychotic monotherapy for 6 weeks. Their blood DNA was genotyped for OXTR polymorphisms. Their symptom severity was assessed by Positive and Negative Syndrome Scale (PANSS), and the scores were transformed into seven factors (positive, disorganized, negative symptoms apathy/avolition, negative symptoms deficit of expression, hostility, anxiety and depression). Percentage changes in PANSS scores from baseline to week 6 were calculated to quantify antipsychotic responses. We found that OXTR polymorphisms were nominally associated with the severity of overall symptoms (rs237899, β = 1.669, p = 0.019), hostility symptoms (rs237899, β = 0.427, p = 0.044) and anxiety symptoms (rs13316193, β = -0.197, p = 0.038). As for treatment responses, OXTR polymorphisms were nominally associated with the improvement in negative symptoms apathy/avolition (rs2268490, β = 2.235, p = 0.0499). No association between severity or response to treatment and OXTR polymorphisms was found with statistical correction for multiplicity. Overall, our results highlighted the possibility of nominally significant associations of the OXTR gene with the severity and improvement in schizophrenia symptoms. Given the exploratory nature of this study, these associations are indicative of the role of the OXTR gene in the pathology of schizophrenia and may contribute to further elucidate the mechanism of specific symptoms of schizophrenia and to exploit antipsychotics more effective to specific symptoms.