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Background Approximately 30% of individuals with schizophrenia (SZ) are resistant to conventional antipsychotic drug therapy (AP). Of these, one third are also resistant to the second-line treatment, clozapine. Treatment resistance and refractoriness are associated with increased morbidity and disability, making timely detection of these issues critical. Variability in treatment responsiveness is partly genetic, but research has yet to identify variants suitable for personalizing antipsychotic prescriptions. Methods We evaluated potential associations between response to AP and candidate gene variants previously linked to schizophrenia or treatment response. Two groups of patients with SZ were evaluated; one receiving clozapine (n=135) and the other receiving another second-generation AP (n=61). Single-nucleotide polymorphisms (SNPs) in the genes OXT, OXTR, CNR1, DDC, and DRD2 were analyzed. Results Several SNPs were associated with response vs. resistance to AP or clozapine. Conclusions This is the first study of its kind in our admixed Chilean population to address the complete treatment response spectrum. We identified SNPs predictive of treatment-resistant schizophrenia in the genes OXT, CNR1, DDC, and DRD2.

Polymorphisms in Schizophrenia-Related Genes Are Potential Predictors of Antipsychotic Treatment Resistance and Refractoriness