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Article

HTR1A, HTR1B, HTR2A, HTR2C and HTR6 Gene Polymorphisms and Extrapyramidal Side Effects in Haloperidol-Treated Patients with Schizophrenia

1
Faculty of Pharmacy and Biochemistry, University of Zagreb, 10 000 Zagreb, Croatia
2
Department of Psychiatry, University Hospital Centre Zagreb, 10 000 Zagreb, Croatia
3
School of Medicine, University of Zagreb, 10 000 Zagreb, Croatia
4
Laboratory for Molecular Neuropsychiatry, Division of Molecular Medicine, Rudjer Boskovic Institute, 10 000 Zagreb, Croatia
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(7), 2345; https://doi.org/10.3390/ijms21072345
Received: 19 February 2020 / Revised: 20 March 2020 / Accepted: 27 March 2020 / Published: 28 March 2020
(This article belongs to the Special Issue Serotonin in Health and Disease)
Schizophrenia is a serious, chronic psychiatric disorder requiring lifelong treatment. Extrapyramidal side effects (EPS) are common adverse reactions to antipsychotic medications. In addition to the dopaminergic system, serotonergic mechanisms, including serotonin (5-HT) receptors, might be involved in EPS development. This study aimed to examine molecular associations of HTR1A, HTR1B, HTR2A, HTR2C and HTR6 gene polymorphisms with acute EPS in 229 male schizophrenia patients, following two weeks of haloperidol monotherapy. The Simpson–Angus Rating Scale for Extrapyramidal Side Effects (SAS), Barnes Akathisia Rating Scale (BARS) and Extrapyramidal Symptom Rating Scale (ESRS) were used to evaluate EPS severity. Genotyping was performed using real-time PCR, following extraction of blood DNA. Significant acute EPS appeared in 48.03% of schizophrenia patients. For the rs13212041 HTR1B gene polymorphism, affecting microRNA regulation of HTR1B gene expression, a higher frequency of TT carriers was found among haloperidol-treated patients with akathisia when compared to the group without akathisia symptoms. In comparison to C-allele carriers, patients carrying the TT genotype had higher akathisia severity, as determined by the SAS, BARS and ESRS scales. These molecular findings suggest potential involvement of 5-HT1B receptors in akathisia development following haloperidol treatment, as well as possible epigenetic mechanisms of serotonergic modulation associated with antipsychotic-induced EPS. View Full-Text
Keywords: schizophrenia; haloperidol; acute extrapyramidal side effects; serotonin receptors; gene polymorphisms; HTR1B gene polymorphism; akathisia schizophrenia; haloperidol; acute extrapyramidal side effects; serotonin receptors; gene polymorphisms; HTR1B gene polymorphism; akathisia
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MDPI and ACS Style

Grubor, M.; Zivkovic, M.; Sagud, M.; Nikolac Perkovic, M.; Mihaljevic-Peles, A.; Pivac, N.; Muck-Seler, D.; Svob Strac, D. HTR1A, HTR1B, HTR2A, HTR2C and HTR6 Gene Polymorphisms and Extrapyramidal Side Effects in Haloperidol-Treated Patients with Schizophrenia. Int. J. Mol. Sci. 2020, 21, 2345. https://doi.org/10.3390/ijms21072345

AMA Style

Grubor M, Zivkovic M, Sagud M, Nikolac Perkovic M, Mihaljevic-Peles A, Pivac N, Muck-Seler D, Svob Strac D. HTR1A, HTR1B, HTR2A, HTR2C and HTR6 Gene Polymorphisms and Extrapyramidal Side Effects in Haloperidol-Treated Patients with Schizophrenia. International Journal of Molecular Sciences. 2020; 21(7):2345. https://doi.org/10.3390/ijms21072345

Chicago/Turabian Style

Grubor, Mirko, Maja Zivkovic, Marina Sagud, Matea Nikolac Perkovic, Alma Mihaljevic-Peles, Nela Pivac, Dorotea Muck-Seler, and Dubravka Svob Strac. 2020. "HTR1A, HTR1B, HTR2A, HTR2C and HTR6 Gene Polymorphisms and Extrapyramidal Side Effects in Haloperidol-Treated Patients with Schizophrenia" International Journal of Molecular Sciences 21, no. 7: 2345. https://doi.org/10.3390/ijms21072345

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