title: Pharmacogenetics and antipsychotic treatment response.
abstract: Antipsychotic drugs are widely used in the treatment of schizophrenia and psychotic disorder. The lack of antipsychotic response and treatment-induced side-effects, such as neuroleptic syndrome, polydipsia, metabolic syndrome, weight gain, extrapyramidal symptoms, tardive dyskinesia or prolactin increase, are the two main reasons for non-compliance and increased morbidity in schizophrenic patients. During the past decades intensive research has been done in order to determine the influence of genetic variations on antipsychotics dosage, treatment efficacy and safety. The present work reviews the molecular basis of treatment response of schizophrenia. It highlights the most important findings about the impact of functional polymorphisms in genes coding the CYP450 metabolizing enzymes, ABCB1 transporter gene, dopaminergic and serotonergic drug targets (DRD2, DRD3, DRD4, 5-HT1, 5HT-2A, 5HT-2C, 5HT6) as well as genes responsible for metabolism of neurotransmitters and G signalling pathways (5-HTTLPR, BDNF, COMT, RGS4) and points their role as potential biomarkers in everyday clinical practice. Pharmacogenetic testing has predictive power in the selection of antipsychotic drugs and doses tailored according to the patient's genetic profile. In this perception pharmacogenetics could help in the improvement of treatment response by using different medicinal approaches that would avoid potential adverse effects, reduce stabilization time and will advance the prognosis of schizophrenic patients.
authors.affiliation: Pharmaceutical Chemistry Institute, Pharmacy Faculty, Ss. Cyril and Methodius University, Skopje, R. Macedonia.
authors.forename: Z
authors.initials: Z
authors.lastname: Naumovska
authors.affiliation: Pharmaceutical Chemistry Institute, Pharmacy Faculty, Ss. Cyril and Methodius University, Skopje, R. Macedonia.
authors.forename: A K
authors.initials: AK
authors.lastname: Nestorovska
authors.affiliation: University Psychiatry Clinic, Medical Faculty, Ss. Cyril and Methodius University, Skopje, R. Macedonia.
authors.forename: A
authors.initials: A
authors.lastname: Filipce
authors.affiliation: Pharmaceutical Chemistry Institute, Pharmacy Faculty, Ss. Cyril and Methodius University, Skopje, R. Macedonia.
authors.forename: Z
authors.initials: Z
authors.lastname: Sterjev
authors.affiliation: Pharmaceutical Chemistry Institute, Pharmacy Faculty, Ss. Cyril and Methodius University, Skopje, R. Macedonia.
authors.forename: K
authors.initials: K
authors.lastname: Brezovska
authors.affiliation: Pharmaceutical Chemistry Institute, Pharmacy Faculty, Ss. Cyril and Methodius University, Skopje, R. Macedonia.
authors.forename: A
authors.initials: A
authors.lastname: Dimovski
authors.affiliation: Pharmaceutical Chemistry Institute, Pharmacy Faculty, Ss. Cyril and Methodius University, Skopje, R. Macedonia.
authors.forename: L J
authors.initials: LJ
authors.lastname: Suturkova
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001480:Basal Ganglia Diseases / Q000139:chemically induced / Q000235:genetics; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics; D002394:Catechol O-Methyltransferase / Q000235:genetics; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D004409:Dyskinesia, Drug-Induced / Q000235:genetics; D006801:Humans; D024821:Metabolic Syndrome / Q000139:chemically induced / Q000235:genetics; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D011618:Psychotic Disorders / Q000188:drug therapy*; D020710:RGS Proteins / Q000235:genetics; D011954:Receptors, Dopamine / Q000235:genetics*; D011985:Receptors, Serotonin / Q000235:genetics*; D012559:Schizophrenia / Q000188:drug therapy*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics; D016896:Treatment Outcome; D015430:Weight Gain / Q000235:genetics
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D014150:Antipsychotic Agents; D019208:Brain-Derived Neurotrophic Factor; D020710:RGS Proteins; D011954:Receptors, Dopamine; D011985:Receptors, Serotonin; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; C098799:RGS4 protein; C579455:BDNF protein, human; D003577:Cytochrome P-450 Enzyme System; C588010:COMT protein, human; D002394:Catechol O-Methyltransferase