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. 2023 Jul 24;11(7):2088.
doi: 10.3390/biomedicines11072088.

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

Antonio Del Casale  1   2 , Maurizio Simmaco  3   4 , Martina Nicole Modesti  3 , Clarissa Zocchi  3 , Jan Francesco Arena  3 , Irene Bilotta  3 , Alessandro Alcibiade  3 , Giuseppe Sarli  3 , Lorenzo Cutillo  3 , Giulia Antonelli  3 , Enrico La Spina  3 , Ottavia De Luca  3   4 , Robert Preissner  5 , Marina Borro  3   4 , Giovanna Gentile  3   4 , Paolo Girardi  1 , Maurizio Pompili  2   3
Affiliations

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

Antonio Del Casale et al. Biomedicines. .

Abstract

Background: The objective of this study was to investigate the DRD2 rs1800497, rs1799732, rs1801028, DRD3 rs6280, and HTR2A 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 DRD3 rs6280 C|T (OR = 22.195) and T|T (OR = 18.47) vs. C|C, HTR2A rs7997012 A|G vs. A|A (OR = 6.859) and vs. G|G (OR = 2.879), and DRD2 rs1799732 I|I vs. D|I (OR = 12.079) genotypes.

Conclusions: A diagnosis of schizophrenia and the DRD2 rs1799732, DRD3 rs6280, and HTR2A rs7997012 genotypes can predict high treatment resistance to SGAs.

Keywords: 5-hydroxytryptamine receptors; antipsychotic agents; dopamine receptors; drug resistance; pharmacogenomic variants; precision medicine.

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Conflict of interest statement

In the last two years, MP has received lectures or advisory board honoraria or engaged in clinical trial activities with Angelini Pharma, Lundbeck, Janssen, Pfizer, MSD, Rovi, and Recordati, which are unrelated to this study; ADC has received advisory board honoraria from Fidia, which are unrelated to this study. All the other authors declare no conflict of interest.

References

    1. López-Muñoz F., Alamo C., Cuenca E., Shen W., Clervoy P., Rubio G. History of the Discovery and Clinical Introduction of Chlorpromazine. Ann. Clin. Psychiatry. 2005;17:113–135. doi: 10.1080/10401230591002002. - DOI - PubMed
    1. Howes O.D., Kapur S. The Dopamine Hypothesis of Schizophrenia: Version III—The Final Common Pathway. Schizophr. Bull. 2009;35:549–562. doi: 10.1093/schbul/sbp006. - DOI - PMC - PubMed
    1. American Psychiatric Association . The American Psychiatric Association Practice Guideline for the Treatment of Patients with Schizophrenia. American Psychiatric Association Publishing; Washington, DC, USA: 2020. - DOI - PMC - PubMed
    1. National Institute for Health and Care Excellence (NICE) Psychosis and Schizophrenia in Adults: Prevention and Management Clinical Guideline. National Institute for Health and Care Excellence; London, UK: 2014. - PubMed
    1. National Institute for Health and Care Excellence (NICE) Bipolar Disorder: Assessment and Management Clinical Guideline. National Institute for Health and Care Excellence; London, UK: 2014.

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