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. 2022 Sep 28;25(9):701-708.
doi: 10.1093/ijnp/pyac025.

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

Alejandra Zazueta  1 , Tito Castillo  2 , Álvaro Cavieres  3 , René González  2 , Maximiliano Abarca  3 , Rodrigo R Nieto  4   5   6 , Javier Deneken  4   7 , Cristian Araneda  8 , Pablo R Moya  2   9 , M Leonor Bustamante  10   7
Affiliations

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

Alejandra Zazueta et al. Int J Neuropsychopharmacol. .

Abstract

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 SZ 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, to our knowledge, in our admixed Chilean population to address the complete treatment response spectrum. We identified SNPs predictive of treatment-resistant SZ in the genes OXT, CNR1, DDC, and DRD2.

Keywords: Schizophrenia; antipsychotics; clozapine; treatment refractoriness; treatment resistance.

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Figures

Figure 1.
Figure 1.
Schematic representation of study design.
Figure 2.
Figure 2.
(A) Distribution of positive symptoms in clozapine and second-generation antipsychotics (SGAP) groups. (B) Distribution of negative symptoms in clozapine and SGAP groups.
Figure 3.
Figure 3.
Single-nucleotide polymorphism (SNPs) with significant differences in the clozapine vs. second-generation antipsychotics groups.
Figure 4.
Figure 4.
Brief Psychiatric Rating Scale (BPRS) scores for the whole treatment-resistant schizophrenia (TRS) group by DRD2 rs179978 variant.
See this image and copyright information in PMC

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