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

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

doi:10.3390/biomedicines11072088

Biomedicines (Jul 2023)

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

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

Affiliations

Antonio Del Casale: Department of Dynamic and Clinical Psychology and Health Studies, Faculty of Medicine and Psychology, Sapienza University of Rome, 00185 Rome, Italy
Maurizio Simmaco: Department of Neuroscience, Mental Health and Sensory Organs (NESMOS), Faculty of Medicine and Psychology, Sapienza University of Rome, 00185 Rome, Italy
Martina Nicole Modesti: Department of Neuroscience, Mental Health and Sensory Organs (NESMOS), Faculty of Medicine and Psychology, Sapienza University of Rome, 00185 Rome, Italy
Clarissa Zocchi: Department of Neuroscience, Mental Health and Sensory Organs (NESMOS), Faculty of Medicine and Psychology, Sapienza University of Rome, 00185 Rome, Italy
Jan Francesco Arena: Department of Neuroscience, Mental Health and Sensory Organs (NESMOS), Faculty of Medicine and Psychology, Sapienza University of Rome, 00185 Rome, Italy
Irene Bilotta: Department of Neuroscience, Mental Health and Sensory Organs (NESMOS), Faculty of Medicine and Psychology, Sapienza University of Rome, 00185 Rome, Italy
Alessandro Alcibiade: Department of Neuroscience, Mental Health and Sensory Organs (NESMOS), Faculty of Medicine and Psychology, Sapienza University of Rome, 00185 Rome, Italy
Giuseppe Sarli: Department of Neuroscience, Mental Health and Sensory Organs (NESMOS), Faculty of Medicine and Psychology, Sapienza University of Rome, 00185 Rome, Italy
Lorenzo Cutillo: Department of Neuroscience, Mental Health and Sensory Organs (NESMOS), Faculty of Medicine and Psychology, Sapienza University of Rome, 00185 Rome, Italy
Giulia Antonelli: Department of Neuroscience, Mental Health and Sensory Organs (NESMOS), Faculty of Medicine and Psychology, Sapienza University of Rome, 00185 Rome, Italy
Enrico La Spina: Department of Neuroscience, Mental Health and Sensory Organs (NESMOS), Faculty of Medicine and Psychology, Sapienza University of Rome, 00185 Rome, Italy
Ottavia De Luca: Department of Neuroscience, Mental Health and Sensory Organs (NESMOS), Faculty of Medicine and Psychology, Sapienza University of Rome, 00185 Rome, Italy
Robert Preissner: Structural Bioinformatics Group, Institute for Physiology, Charité—University Medicine Berlin, 10115 Berlin, Germany
Marina Borro: Department of Neuroscience, Mental Health and Sensory Organs (NESMOS), Faculty of Medicine and Psychology, Sapienza University of Rome, 00185 Rome, Italy
Giovanna Gentile: Department of Neuroscience, Mental Health and Sensory Organs (NESMOS), Faculty of Medicine and Psychology, Sapienza University of Rome, 00185 Rome, Italy
Paolo Girardi: Department of Dynamic and Clinical Psychology and Health Studies, Faculty of Medicine and Psychology, Sapienza University of Rome, 00185 Rome, Italy
Maurizio Pompili: Unit of Psychiatry, ‘Sant’Andrea’ University Hospital, 00189 Rome, Italy

DOI: https://doi.org/10.3390/biomedicines11072088
Journal volume & issue: Vol. 11, no. 7
p. 2088

Abstract

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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.

Published in Biomedicines

ISSN: 2227-9059 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Science: Biology (General)
Website: http://www.mdpi.com/journal/biomedicines

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