DRD2, DRD3, and HTR2A Single-Nucleotide Polymorphisms Involvement in High Treatment Resistance to Atypical Antipsychotic Drugs.

Background: The objective of this study was to investigate the rs1800497, rs1799732, rs1801028, rs6280, and rs6314, rs7997012, and rs6311 single-nucleotide polymorphism (SNP) correlations with resistance to second-generation antipsychotics (SGAs) in a real-world sample of patients with treatment-resistant mental disorders.

Methods: We divided 129 participants into a high treatment resistance (HTR) group (current treatment with two SGAs, or clozapine, or classic neuroleptics for a failure of previous SGAs trials) and a low treatment resistance (LTR) group (current treatment with one atypical antipsychotic). We used Next-Generation Sequencing on DNA isolated from peripheral blood samples to analyze the polymorphisms. We performed logistic regression to search for predictors of HTR membership.

Results: A diagnosis of schizophrenia significantly predicted the HTR membership compared to other diagnoses. Other predictors were the rs6280 C|T (OR = 22.195) and T|T (OR = 18.47) vs. C|C, rs7997012 A|G vs. A|A (OR = 6.859) and vs. G|G (OR = 2.879), and rs1799732 I|I vs. D|I (OR = 12.079) genotypes.

Conclusions: A diagnosis of schizophrenia and the rs1799732, rs6280, and rs7997012 genotypes can predict high treatment resistance to SGAs.