title: Treatment-resistant schizophrenia and DAT and SERT polymorphisms.
abstract: One fifth to one third of all patients diagnosed with schizophrenia are resistant to drug treatment, which makes it a major clinical challenge. Genetic studies have focused on the association between treatment resistant schizophrenia (TRS) and a number of candidate genes, including serotonin and dopamine system genes. We explored associations between carefully characterized TRS and DAT-VNTR, SERT-PR and SERT-in2 polymorphisms. There were 173 patients enrolled in the study that were clinically evaluated using Positive and Negative Syndrome Scale and Clinical Global Impressions Scales and divided into two groups based on treatment resistance (92 patients in TRS group). Patients with a combination of SERT-in2 ll and DAT 9/10, 9/11, 9/9 and 6/6 genotypes were more likely to have TRS, compared to those with 10/10 or 10/12 genotype (OR=5.1; 95% CI=1.6-16.8). In the group of patients with DAT 10/10 or 10/12 genotype, those who also shared SERT-in2 ls or ss genotype were more likely to have TRS, compared to ll genotype carriers (OR=2.7; 95% CI=1.0-7.0). The model in which interaction between SERT-in2 and DAT polymorphisms is linked to TRS can possibly explain contradictory previous results regarding role of DAT and SERT in TRS, but further research is needed.
authors.affiliation: University Psychiatric Hospital Vrapce, Zagreb, Croatia. Electronic address: petar.bilic@bolnica-vrapce.hr.
authors.forename: Petar
authors.initials: P
authors.lastname: Bilic
authors.affiliation: University Psychiatric Hospital Vrapce, Zagreb, Croatia.
authors.forename: Vlado
authors.initials: V
authors.lastname: Jukic
authors.affiliation: University Psychiatric Hospital Vrapce, Zagreb, Croatia.
authors.forename: Maja
authors.initials: M
authors.lastname: Vilibic
authors.affiliation: University Psychiatric Hospital Vrapce, Zagreb, Croatia.
authors.forename: Aleksandar
authors.initials: A
authors.lastname: Savic
authors.affiliation: Clinical Institute of Laboratory Diagnosis, University Hospital Centre Zagreb, Zagreb, Croatia.
authors.forename: Nada
authors.initials: N
authors.lastname: Bozina
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics*; D004351:Drug Resistance / Q000235:genetics*; D005260:Female; D006801:Humans; D054643:INDEL Mutation; D008297:Male; D008875:Middle Aged; D018598:Minisatellite Repeats / Q000235:genetics; D020125:Mutation, Missense; D011110:Polymorphism, Genetic; D012559:Schizophrenia / Q000188:drug therapy* / Q000235:genetics*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*
chemical_list: D014150:Antipsychotic Agents; D050483:Dopamine Plasma Membrane Transport Proteins; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins
keywords: DAT; SERT; Treatment-resistant schizophrenia; VNTR