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

ORCID
0000-0003-2427-6944
Affiliation
Department of Dynamic and Clinical Psychology and Health Studies, Faculty of Medicine and Psychology, Sapienza University of Rome, 00185 Rome, Italy;
Del Casale, Antonio;
Affiliation
Department of Neuroscience, Mental Health and Sensory Organs (NESMOS), Faculty of Medicine and Psychology, Sapienza University of Rome, 00185 Rome, Italy
Simmaco, Maurizio;
ORCID
0000-0001-8540-4407
Affiliation
Department of Neuroscience, Mental Health and Sensory Organs (NESMOS), Faculty of Medicine and Psychology, Sapienza University of Rome, 00185 Rome, Italy
Modesti, Martina Nicole;
Affiliation
Department of Neuroscience, Mental Health and Sensory Organs (NESMOS), Faculty of Medicine and Psychology, Sapienza University of Rome, 00185 Rome, Italy
Zocchi, Clarissa;
ORCID
0000-0003-1477-2645
Affiliation
Department of Neuroscience, Mental Health and Sensory Organs (NESMOS), Faculty of Medicine and Psychology, Sapienza University of Rome, 00185 Rome, Italy
Arena, Jan Francesco;
Affiliation
Department of Neuroscience, Mental Health and Sensory Organs (NESMOS), Faculty of Medicine and Psychology, Sapienza University of Rome, 00185 Rome, Italy
Bilotta, Irene;
Affiliation
Department of Neuroscience, Mental Health and Sensory Organs (NESMOS), Faculty of Medicine and Psychology, Sapienza University of Rome, 00185 Rome, Italy
Alcibiade, Alessandro;
Affiliation
Department of Neuroscience, Mental Health and Sensory Organs (NESMOS), Faculty of Medicine and Psychology, Sapienza University of Rome, 00185 Rome, Italy
Sarli, Giuseppe;
Affiliation
Department of Neuroscience, Mental Health and Sensory Organs (NESMOS), Faculty of Medicine and Psychology, Sapienza University of Rome, 00185 Rome, Italy
Cutillo, Lorenzo;
Affiliation
Department of Neuroscience, Mental Health and Sensory Organs (NESMOS), Faculty of Medicine and Psychology, Sapienza University of Rome, 00185 Rome, Italy
Antonelli, Giulia;
Affiliation
Department of Neuroscience, Mental Health and Sensory Organs (NESMOS), Faculty of Medicine and Psychology, Sapienza University of Rome, 00185 Rome, Italy
La Spina, Enrico;
ORCID
0000-0002-3852-4585
Affiliation
Department of Neuroscience, Mental Health and Sensory Organs (NESMOS), Faculty of Medicine and Psychology, Sapienza University of Rome, 00185 Rome, Italy
De Luca, Ottavia;
ORCID
0000-0002-2407-1087
Affiliation
Structural Bioinformatics Group, Institute for Physiology, Charité—University Medicine Berlin, 10115 Berlin, Germany
Preissner, Robert;
ORCID
0000-0002-7839-9125
Affiliation
Department of Neuroscience, Mental Health and Sensory Organs (NESMOS), Faculty of Medicine and Psychology, Sapienza University of Rome, 00185 Rome, Italy
Borro, Marina;
ORCID
0000-0001-8667-3094
Affiliation
Department of Neuroscience, Mental Health and Sensory Organs (NESMOS), Faculty of Medicine and Psychology, Sapienza University of Rome, 00185 Rome, Italy
Gentile, Giovanna;
Affiliation
Department of Dynamic and Clinical Psychology and Health Studies, Faculty of Medicine and Psychology, Sapienza University of Rome, 00185 Rome, Italy;
Girardi, Paolo;
ORCID
0000-0003-1886-4977
Affiliation
Unit of Psychiatry, ‘Sant’Andrea’ University Hospital, 00189 Rome, Italy
Pompili, Maurizio

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.

Category

Editor:
Lentini, Giovanni; Mignani, Serge
Published in:
Biomedicines  
Vol. 11, No. 7 (24.07.2023)
Volume:
11
No.:
7
Date Issued:
24.07.2023
DOI:
10.3390/biomedicines11072088
Language:
English
Type of Resource:
Text
Keywords:
antipsychotic agents; dopamine receptors; 5-hydroxytryptamine receptors; drug resistance; pharmacogenomic variants; precision medicine
Subject of DNB:
610 Medical sciences Medicine
DDC:
610 Medizin und Gesundheit

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