title: Investigation of the phenylalanine hydroxylase gene and tardive dyskinesia.
abstract: Phenylketonuria (PKU), an inborn error of phenylalanine metabolism, has been shown to be a risk factor for tardive dyskinesia (TD). In male psychiatric patients there was a significant relationship between TD and measures of plasma phenylalanine following ingestion of a standardized phenylalanine dose that was indicative of higher brain availability of phenylalanine in patients with TD. In addition, a medical food formulation consisting of branched chain amino acids, which compete with phenylalanine for transport across the blood-brain barrier, has been demonstrated to be an efficacious treatment for TD. Cumulatively these findings suggested that TD was related to phenylalanine metabolism and thus that sequence variants in the gene for phenylalanine hydroxylase (PAH), the rate-limiting enzyme in the catabolism of phenylalanine, could be associated with TD susceptibility. Genetic screening of PAH in a group of 123 psychiatric patients revealed ten sequence polymorphisms and two mutations, but none appeared to be a significant risk factor for TD.
authors.affiliation: Movement Disorders and Molecular Psychiatry Division, Nathan Kline Institute for Psychiatric Research, New York State Office of Mental Health, Orangeburg, New York 10962, USA.
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Richardson
authors.forename: Helen M
authors.initials: HM
authors.lastname: Chao
authors.forename: Laura L
authors.initials: LL
authors.lastname: Read
authors.forename: James D
authors.initials: JD
authors.lastname: Clelland
authors.forename: Raymond F
authors.initials: RF
authors.lastname: Suckow
mesh_terms: D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use; D004409:Dyskinesia, Drug-Induced / Q000097:blood / Q000209:etiology*; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation; D010649:Phenylalanine / Q000097:blood; D010651:Phenylalanine Hydroxylase / Q000235:genetics* / Q000378:metabolism; D011110:Polymorphism, Genetic; D011618:Psychotic Disorders / Q000097:blood / Q000188:drug therapy / Q000235:genetics*
chemical_list: D014150:Antipsychotic Agents; D010649:Phenylalanine; D010651:Phenylalanine Hydroxylase