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
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.
