title: Association between cytochrome P4502D6 (CYP2D6) genotype, antipsychotic exposure, and abnormal involuntary movement scale (AIMS) score.
abstract: Antipsychotic metabolism cosegregates with the polymorphic cytochrome P4502D6 (CYP2D6) hepatic enzyme. Approximately 5-10% of Caucasians show impaired metabolism associated with nonfunctional alleles. Genotyping determines the number of functional alleles, which is phenotypically not possible. The aim of this study was to investigate associations between CYP2D6 genotype, antipsychotic exposure, and abnormal involuntary movement scale (AIMS) score. Schizophrenic patients (DSM-IV) were genotyped for CYP2D6*1, *3, and *4 alleles by nested polymerase chain reaction. A complete history, including psychiatric symptoms, medications and AIMS score was obtained. Antipsychotic exposure was recorded in dose years [(chlorpromazine equivalents x years)/100]. A linear regression model used AIMS scores as the dependent variable. Genotype, gender, antipsychotic exposure, and interactions were independent variables. The results of the 31 patients studied showed: 20 were homozygous for the *1 allele (*1/*1) and 11 were heterozygous for the *1 allele (i.e. *1/*3 or *4). Age, sex, age of onset, treatment duration, antipsychotic exposure, and AIMS scores did not differ between groups. The interaction between dose years and genotype was significant (P < 0.0055), demonstrating that for (*1/*1) patients, the magnitude of antipsychotic exposure had a greater effect on AIMS score (slope = 0.044) compared with (*1/*3 or *4) patients (slope = 0.001). These results suggest patients with a *3 or *4 allele may have a higher risk for developing antipsychotic induced abnormal movements.
authors.affiliation: College of Pharmacy, University of Iowa, Iowa City, USA. vicki-ellingrod@uiowa.edu
authors.forename: V L
authors.initials: VL
authors.lastname: Ellingrod
authors.forename: S K
authors.initials: SK
authors.lastname: Schultz
authors.forename: S
authors.initials: S
authors.lastname: Arndt
mesh_terms: D017668:Age of Onset; D000483:Alleles; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000493:pharmacokinetics; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D004409:Dyskinesia, Drug-Induced / Q000201:enzymology* / Q000453:epidemiology / Q000209:etiology / Q000235:genetics; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008658:Inactivation, Metabolic / Q000235:genetics; D016014:Linear Models; D016133:Polymerase Chain Reaction; D012306:Risk; D012559:Schizophrenia / Q000150:complications / Q000188:drug therapy / Q000453:epidemiology; D012720:Severity of Illness Index
chemical_list: D014150:Antipsychotic Agents; D019389:Cytochrome P-450 CYP2D6