{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T17:51:12Z","timestamp":1788544272691,"version":"build-2803163510"},"reference-count":80,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2020,3,28]],"date-time":"2020-03-28T00:00:00Z","timestamp":1585353600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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\u2013Angus 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.<\/jats:p>","DOI":"10.3390\/ijms21072345","type":"journal-article","created":{"date-parts":[[2020,4,1]],"date-time":"2020-04-01T03:44:13Z","timestamp":1585712653000},"page":"2345","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["HTR1A, HTR1B, HTR2A, HTR2C and HTR6 Gene Polymorphisms and Extrapyramidal Side Effects in Haloperidol-Treated Patients with Schizophrenia"],"prefix":"10.3390","volume":"21","author":[{"given":"Mirko","family":"Grubor","sequence":"first","affiliation":[{"name":"Faculty of Pharmacy and Biochemistry, University of Zagreb, 10 000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maja","family":"Zivkovic","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University Hospital Centre Zagreb, 10 000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Sagud","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University Hospital Centre Zagreb, 10 000 Zagreb, Croatia"},{"name":"School of Medicine, University of Zagreb, 10 000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matea","family":"Nikolac Perkovic","sequence":"additional","affiliation":[{"name":"Laboratory for Molecular Neuropsychiatry, Division of Molecular Medicine, Rudjer Boskovic Institute, 10 000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alma","family":"Mihaljevic-Peles","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University Hospital Centre Zagreb, 10 000 Zagreb, Croatia"},{"name":"School of Medicine, University of Zagreb, 10 000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nela","family":"Pivac","sequence":"additional","affiliation":[{"name":"Laboratory for Molecular Neuropsychiatry, Division of Molecular Medicine, Rudjer Boskovic Institute, 10 000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorotea","family":"Muck-Seler","sequence":"additional","affiliation":[{"name":"Laboratory for Molecular Neuropsychiatry, Division of Molecular Medicine, Rudjer Boskovic Institute, 10 000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6200-2405","authenticated-orcid":false,"given":"Dubravka","family":"Svob Strac","sequence":"additional","affiliation":[{"name":"Laboratory for Molecular Neuropsychiatry, Division of Molecular Medicine, Rudjer Boskovic Institute, 10 000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,3,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1753","DOI":"10.1056\/NEJMra1808803","article-title":"Schizophrenia","volume":"381","author":"Marder","year":"2019","journal-title":"N. 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