TY - JOUR
T1 - Polymorphisms in Schizophrenia-Related Genes Are Potential Predictors of Antipsychotic Treatment Resistance and Refractoriness
AU - Zazueta, Alejandra
AU - Castillo, Tito
AU - Cavieres, Álvaro
AU - González, René
AU - Abarca, Maximiliano
AU - Nieto, Rodrigo R.
AU - Deneken, Javier
AU - Araneda, Cristian
AU - Moya, Pablo R.
AU - Bustamante, M. Leonor
N1 - Publisher Copyright:
© The Author(s) 2022. Published by Oxford University Press on behalf of CINP.
PY - 2022/9/1
Y1 - 2022/9/1
N2 - 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.
AB - 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.
KW - antipsychotics
KW - clozapine
KW - Schizophrenia
KW - treatment refractoriness
KW - treatment resistance
UR - http://www.scopus.com/inward/record.url?scp=85139375182&partnerID=8YFLogxK
U2 - 10.1093/ijnp/pyac025
DO - 10.1093/ijnp/pyac025
M3 - Article
C2 - 35416253
AN - SCOPUS:85139375182
SN - 1461-1457
VL - 25
SP - 701
EP - 708
JO - International Journal of Neuropsychopharmacology
JF - International Journal of Neuropsychopharmacology
IS - 9
ER -