The association between 5-HT1B serotonin receptor gene polymorphism and acute extrapyramidal side effects in haloperidol-treated patients with schizophrenia

Shizofrenija predstavlja ozbiljan kronični psihijatrijski poremećaj čija je neurobiološka podloga još uvijek nedovoljno poznata. Bolest se liječi tzv. tipičnim i atipičnim antipsihoticima, no kod dijela bolesnika javljaju se negativni popratni učinci koji značajno otežavaju liječenje dovodeći do prekida terapije i učestalog povratka bolesti. Najpoznatiji popratni učinci tipičnih antipsihotika su akutne (distonija, parkinsonizam, akatizija) i kronične (tardivna diskinezija) ekstrapiramidne nuspojave (EPS), dok su najčešće nuspojave atipičnih antipsihotika povećanje tjelesne težine i metabolički sindrom. Atipični antipsihotici razlikuju se od tipičnih po većem afinitetu za serotoninske 5-HT2 receptore u odnosu na dopaminske D2 receptore, te po bržoj disocijaciji s D2 receptora. Saznanja o međudjelovanju dopaminskog i serotoninskog sustava u mozgu potaknula su pitanja o mogućem utjecaju serotoninskog sustava na pojavu EPS. Stoga je cilj istraživanja bio utvrditi moguću povezanost polimorfizma u genu za serotoninski receptor 5-HT1B u oboljelih od shizofrenije, s pojavom akutnih ekstrapiramidnih nuspojava nakon liječenja tipičnim antipsihotikom haloperidolom. U istraživanju je utvrđena značajna povezanost polimorfizma rs132120411 u genu za serotoninski 5-HT1B receptor s razvojem akatizije u bolesnika sa shizofrenijom nakon terapije haloperidolom. Dobiveni rezultati trebali bi pomoći kliničarima da individualiziraju farmakoterapiju, te da prevencijom neželjenih nuspojava antipsihotika povećaju uspješnost liječenja i kvalitetu života oboljelih od shizofrenije.Schizophrenia is a serious chronic psychiatric condition with neurobiological basis still largely unknown. Therapy consists of typical and atypical antipsychotic; however some patients develop side effects that severely affect treatment outcomes and lead to discontinuation of therapy and frequent relapse. Well known side effects of typical antipsychotics are acute (dystonia, parkinsonism, akathisia) and chronic (tardive dyskinesia) extrapyramidal side effects (EPS), while metabolic syndrome and weight gain are main side effects of atypical antipsychotics. Atypical antipsychotics differ from typical in higher affinity for serotonin 5-HT receptors and faster dissociation from dopamine D2 receptors. Findings on various interactions between serotonin and dopamine systems in the brain have raised questions about possible involvement of serotonin in EPS. Therefore, the aim of this research was to determine the possible association between rs13212041 polymorphism in the gene for the serotonin 5-HT1B receptor in patients with schizophrenia, with the development of acute EPS after treatment with typical antipsychotic drug haloperidol. The study found significant association of rs132120411 polymorphism in the gene coding for the serotonin 5-HT1B receptor with the development of akathisia in schizophrenia patients following haloperidol therapy. The results should help clinicians to individualize the pharmacotherapy and by preventing the unwanted side effects of antipsychotics to increase the treatment efficacy and quality of life of schizophrenia patients