title: Candidate gene analysis of pharmacodynamic targets for antipsychotic dosage.
abstract: OBJECTIVE
  In order to administer antipsychotic medication with the most beneficial outcome, the appropriate drug and dose needs to be identified. Though often not considered in pharmacogenetic studies, dosage plays an important role in treatment outcome. This study set out to analyze the association between 109 SNPs and antipsychotic dosage among schizophrenia patients. In a previous study, we tested 134 SNPs in regards to antipsychotic dosage. In the current study, we tested additional markers in the same candidate genes that we investigated in the previous study to confirm our previous findings.
  
  
  METHODS
  We included 263 participants with schizophrenia spectrum disorders between the ages of 18-75. Each participant was assessed cross-sectionally to collect clinical and antipsychotic treatment information through a semi-structured interview. The antipsychotic dosage for each individual was standardized according to chlorpromazine equivalents (CPZe), defined daily dose, and the percentage of maximum dosage (PM%). For each participant, 109 SNPs from 29 candidate genes were imputed or genotyped using a Customized Illumina Chip.
  
  
  RESULTS
  Polymorphisms in the GABRB1 gene were significantly associated with higher antipsychotic dosage according to CPZe and PM% standardization.
  
  
  CONCLUSIONS
  Our analysis suggests that variation in the GABRB1 gene may be significantly associated with antipsychotic dosage according to CPZe and PM% standardization. Antipsychotic dosage remains an integral measure for treatment response that warrants future pharmacogenetic testing and studies with larger sample sizes.
authors.affiliation: Institute of Medical Science, Faculty of Medicine, University of Toronto, 1 King's College Circle, Room 2374, Toronto, ON M5S 1A8, Canada.|EEG & Genetics Group, Centre for Addiction & Mental Health, 250 College Street, Toronto, ON, M5T 1R8, Canada.
authors.forename: Nuwan C
authors.initials: NC
authors.lastname: Hettige
authors.affiliation: EEG & Genetics Group, Centre for Addiction & Mental Health, 250 College Street, Toronto, ON, M5T 1R8, Canada.
authors.forename: Gustavo H F
authors.initials: GH
authors.lastname: de Moraes
authors.affiliation: Institute of Medical Science, Faculty of Medicine, University of Toronto, 1 King's College Circle, Room 2374, Toronto, ON M5S 1A8, Canada.|Department of Psychiatry, University of Toronto, 250 College Street, Toronto, ON, Canada.
authors.forename: James L
authors.initials: JL
authors.lastname: Kennedy
authors.affiliation: Institute of Medical Science, Faculty of Medicine, University of Toronto, 1 King's College Circle, Room 2374, Toronto, ON M5S 1A8, Canada.|EEG & Genetics Group, Centre for Addiction & Mental Health, 250 College Street, Toronto, ON, M5T 1R8, Canada.|Department of Psychiatry, University of Toronto, 250 College Street, Toronto, ON, Canada.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: De Luca
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage*; D002746:Chlorpromazine / Q000008:administration & dosage; D005260:Female; D056726:Genetic Association Studies; 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
chemical_list: D014150:Antipsychotic Agents; D002746:Chlorpromazine
keywords: CPZe; antipsychotics; defined daily dose; dosage; genetics; schizophrenia