Polimorfizam gena za serotoninski receptor 5-HT1A i motoričke popratne pojave antipsihotika haloperidola

master's thesis

• Title (english): Serotonin 5-HT1A receptor gene polymorphisms and motoric side effects of antipsychotic drug haloperidol
• Author: Andrea Varga
• Mentor: Dubravka Švob Štrac (mentor)
• Mentor: Domagoj Đikić (mentor)
• Committee member: Domagoj Đikić (predsjednik povjerenstva)
• Committee member: Renata Šoštarić (član povjerenstva)
• Committee member: Petar Kružić (član povjerenstva)
• Committee member: Vesna Benković (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2016-07-13, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Antipsihotički lijekovi se koriste u liječenju psihotičnih poremećaja (deluzija, halucinacija, poremećaja razmišljanja) u shizofreniji, ali i psihoza povezanih sa depresijom, bipolarnim poremećajem i Alzheimerovom bolešću. Dvije glavne vrste ovih lijekova su tzv. tipični i atipični antipsihotici. Na žalost, u jednom dijelu bolesnika javljaju se neželjeni popratni učinci liječenja antipsihoticima koji često dovode do prekida terapije i povratka simptoma bolesti. Najpoznatiji popratni učinci tipičnih antipsihotika su motoričke popratne pojave poput distonije, parkinsonizma, akatizije i tardivne diskinezije, koje nastaju primarno zbog blokade dopaminskih receptora u nigrostriatumu i posljedične prekomjerne aktivnosti acetilkolinskog sustava. Međutim, s obzirom da postoje jake neuroanatomske i funkcionalne interakcije serotoninskog i dopaminskog sustava, te da serotoninski sustav u velikoj mjeri regulira i modulira aktivnost dopaminskog sustava, kao i obratno, moguće je da određene varijacije gena serotoninskih receptora mogu utjecati na razvoj motoričkih popratnih pojava tipičnih antipsihotika, koji svoje učinke ostvaruju primarno putem dopaminskih receptora. Stoga, da bi razjasnili ulogu gena serotoninskih receptora u razvoju ovih motoričkih nuspojava, cilj ovog diplomskog rada bio je istražiti moguću povezanost dvaju polimorfizama u genu za serotoninski 5-HT1A receptor s razvojem motoričkih popratnih pojava nakon primjene tipičnog antipsihotika haloperidola u osoba oboljelih od shizofrenije. Dobiveni rezultati nisu uputili na genotipsku i haplotipsku povezanost istraživanih polimorfizama gena 5-HT1A sa motoričkim popratnim pojavama antipsihotika haloperidola u oboljelih od shizofrenije.

Abstract (english)

Antipsychotic drugs are used in the treatment of psychotic disorders (delusions, hallucinations, thought disorders) in schizophrenia, and psychosis related to depression, bipolar disorder, and Alzheimer's disease. Two main types of these drugs are called typical and atypical antipsychotics. Unfortunately, some patients following antipsychotics treatment develop unwanted side effects, which often lead to treatment discontinuation and symptom relapse. The best-known side effects of typical antipsychotics are motor side effects such as dystonia, Parkinsonism, akathisia, and tardive dyskinesia, primarily due to the blockade of dopamine receptors in nigrostriatum and consequent excessive activity of acetylcholine system. However, given that there are strong neuroanatomical and functional interactions of serotonergic and dopaminergic systems, and that serotonergic system largely regulates and modulates the activity of dopaminergic system, and vice versa, it is possible that certain variations in the serotonergic genes may affect the development of motor side effects of typical antipsychotics, which act primarily via dopamine receptors. Therefore, in order to clarify the role of serotonin receptor genes in the development of the motor side effects, the aim of this diploma thesis was to investigate the possible association between two polymorphisms, in the gene coding for the serotonin 5-HT1A receptor, with the development of motor side effects following treatment with a typical antipsychotic haloperidol in patients with schizophrenia. Obtained results suggest no genotypic or haplotypic association of investigated polymorphisms in 5-HT1A gene with extrapyramidal side effects of haloperidol in schizophrenia patients.

• Keywords: shizofrenija; motoričke popratne pojave; haloperidol; 5-HT1A; polimorfizmi; rs878567; rs6295; genotip; haplotip
• Keywords (english): schizophrenia; extrapyramidal side effects; haloperidol; 5-HT1A; polymorphisms; rs878567; rs6295; genotype; haplotype
• Language: croatian
• URN:NBN: urn:nbn:hr:217:886129
• Study programme: Title: Experimental Biology; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra eksperimentalne biologije (magistar/magistra eksperimentalne biologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2017-05-12 11:48:41