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

Scientific paper - Original scientific paper

• Author: Mirko Grubor
• Author: Maja Živković
• Author: Marina Šagud
• Author: Matea Nikolac Perković
• Author: Alma Mihaljević-Peleš
• Author: Nela Pivac
• Author: Dorotea Muck-Šeler
• Author: Dubravka Švob Štrac
• Author's institution: University of Zagreb; School of Medicine; (Department of Psychiatry and Psychological Medicine)
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Psychiatry

Abstract (english)

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.

• Keywords (english): Adult; Antipsychotic Agents / adverse effects; Antipsychotic Agents / therapeutic use; Haloperidol / adverse effects; Haloperidol / therapeutic use; Humans; Male; Middle Aged; Polymorphism, Genetic; Receptor, Serotonin, 5-HT1A / genetics; Receptor, Serotonin, 5-HT1B / genetics; Receptor, Serotonin, 5-HT2A / genetics; Receptor, Serotonin, 5-HT2C / genetics; Receptors, Serotonin / genetics; Schizophrenia / drug therapy; Schizophrenia / genetics
• Language: english
• Publication type: Scientific paper - Original scientific paper
• Publication status: Published
• Peer review: Peer review
• Publication version: Published version
• Journal title: International Journal of Molecular Sciences
• Numbering: vol. 21, no. 7, 2345
• e-ISSN: 1422-0067
• DOI: https://doi.org/10.3390/ijms21072345
• URN:NBN: urn:nbn:hr:105:380748
• Publication: 2020-03-28
• Document URL: https://www.mdpi.com/1422-0067/21/7/2345
• Type of resource: Text
• Access conditions: Open access
• Created on: 2021-04-19 11:50:09