title: Use of candidate gene markers to guide antipsychotic dosage adjustment.
abstract: OBJECTIVE
  To improve antipsychotic treatment in schizophrenia patients, many studies have investigated genetic polymorphisms associated with antipsychotic metabolizing enzymes and receptors. While these studies have typically focused on drug response, few have investigated genetic influences on antipsychotic dosage. This study set out to analyze the association between 134 SNPs in 38 candidate genes and antipsychotic dosage in schizophrenia patients.
  
  
  METHODS
  For our analysis, 300 patients with a diagnosis of either schizophrenia or schizoaffective disorder were recruited between the ages of 18 and 75. A cross-sectional assessment was used, in which data were collected from each participant through an interview and self-report questionnaire. Antipsychotic dose was standardized according to the chlorpromazine equivalents, defined daily dose and relative to the maximum dose specified in the product monograph. Participants were genotyped using a Customized Illumina Chip comprising 134 SNPs, and all markers were screened for nominal significance.
  
  
  RESULTS
  The analysis showed a nominally significant association with the GFRA1 gene.
  
  
  CONCLUSIONS
  The common variants investigated in this study had no major influence on the antipsychotic dosage prescribed in study participants. It remains, though, that this strategy may prove valuable clinically and warrants further investigation.
authors.affiliation: Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, 250 College St, Toronto, ON, M5T 1R8, Canada.
authors.forename: Nuwan C
authors.initials: NC
authors.lastname: Hettige
authors.affiliation: Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, 250 College St, Toronto, ON, M5T 1R8, Canada.
authors.forename: Clement
authors.initials: C
authors.lastname: Zai
authors.affiliation: Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, 250 College St, Toronto, ON, M5T 1R8, Canada.
authors.forename: Monica
authors.initials: M
authors.lastname: Hazra
authors.affiliation: Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, 250 College St, Toronto, ON, M5T 1R8, Canada.
authors.forename: Carol
authors.initials: C
authors.lastname: Borlido
authors.affiliation: Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, 250 College St, Toronto, ON, M5T 1R8, Canada.
authors.forename: James L
authors.initials: JL
authors.lastname: Kennedy
authors.affiliation: Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, 250 College St, Toronto, ON, M5T 1R8, Canada.
authors.forename: John
authors.initials: J
authors.lastname: Strauss
authors.affiliation: Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, 250 College St, Toronto, ON, M5T 1R8, Canada.
authors.forename: Bernard
authors.initials: B
authors.lastname: Le Foll
authors.affiliation: Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, 250 College St, Toronto, ON, M5T 1R8, Canada.
authors.forename: Albert
authors.initials: A
authors.lastname: Wong
authors.affiliation: Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, 250 College St, Toronto, ON, M5T 1R8, Canada.
authors.forename: Gary
authors.initials: G
authors.lastname: Remington
authors.affiliation: Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, 250 College St, Toronto, ON, M5T 1R8, Canada. Electronic address: vincenzo_deluca@camh.net.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: De Luca
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents / Q000008:administration & dosage*; D054316:Biomarkers, Pharmacological; D003430:Cross-Sectional Studies; D005260:Female; D060005:Genotyping Techniques; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011618:Psychotic Disorders / Q000188:drug therapy* / Q000235:genetics*; D012559:Schizophrenia / Q000188:drug therapy* / Q000235:genetics*; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D054316:Biomarkers, Pharmacological; C494987:GFRA1 protein, human; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors
keywords: Antipsychotics; CPZe; Defined daily dose; Genetics; Schizophrenia