title: Dehydroepiandrosterone sulphate as a putative protective factor against tardive dyskinesia.
abstract: BACKGROUND
  Tardive dyskinesia (TD) is a potentially irreversible consequence of long term treatment with antipsychotic drugs which is according to a well-known theory believed to be related to oxidative stress induced neurotoxicity. Dehydroepiandrosterone (DHEA) is an endogenous antioxidant with neuroprotective activity. The biosynthesis of DHEA depends upon the activity of cytochrome P450c17α (CYP17). The gene that encodes for CYP17 has a (T34C) single nucleotide polymorphism which enhances CYP17 transcription and expression.
  
  
  OBJECTIVE
  To test the hypothesis that carriership of a more active CYP17 variant would result in higher DHEA(S) levels and protect against neurotoxicity which results in orofaciolingual TD (TDof), limb-truncal TD (TDlt) or both (TDsum).
  
  
  METHODS
  Tardive dyskinesia was assessed cross-sectionally in 146 Caucasian psychiatric inpatients from Siberia.
  
  
  RESULTS
  Patients who are carriers of the Cyp17 genotype CC have less chance of developing TD compared to patients who are carriers of the Cyp17 genotypes TC or TT (p<0.05). However, these carriers have significant lower circulating DHEAS levels compared to carriers of the Cyp17 genotypes TC and TT (p<0.05). Conversely, carriers of the CYP17 T-allele have significant elevated DHEAS levels. After correcting for gender and age no significant relationship between Cyp17 genotype CC, the T-allelle and the C-allele and the DHEAS concentration of patients was observed.
  
  
  CONCLUSIONS
  Although an association between the CYP17 CC genotype and TD is indicated, our findings do not support the hypothesis that this is mediated through increased DHEA(S) levels. We believe that the relationship between this polymorphism and neuroprotective effects of steroids is more complex and cannot be elucidated without taking the posttranslational regulation of the enzyme into account.
authors.affiliation: Mental Health Research Institute, Tomsk, Russia; National Research Tomsk Polytechnic University, Tomsk, Russia.
authors.forename: Svetlana A
authors.initials: SA
authors.lastname: Ivanova
authors.affiliation: Department of Pharmacy, University of Groningen, Groningen, The Netherlands.
authors.forename: Lisanne M
authors.initials: LM
authors.lastname: Geers
authors.affiliation: Department of Pharmacy, University of Groningen, Groningen, The Netherlands; Parnassia Group, Pharmacy Haaglanden, The Hague, The Netherlands.
authors.forename: Asmar F Y
authors.initials: AF
authors.lastname: Al Hadithy
authors.affiliation: Department of Pharmacy, University of Groningen, Groningen, The Netherlands; Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada.
authors.forename: Petros
authors.initials: P
authors.lastname: Pechlivanoglou
authors.affiliation: Mental Health Research Institute, Tomsk, Russia.
authors.forename: Arkadiy V
authors.initials: AV
authors.lastname: Semke
authors.affiliation: Mental Health Research Institute, Tomsk, Russia.
authors.forename: Natalia M
authors.initials: NM
authors.lastname: Vyalova
authors.affiliation: Mental Health Research Institute, Tomsk, Russia.
authors.forename: Evgeniy V
authors.initials: EV
authors.lastname: Rudikov
authors.affiliation: Mental Health Research Institute, Tomsk, Russia; National Research Tomsk Polytechnic University, Tomsk, Russia.
authors.forename: Olga Y
authors.initials: OY
authors.lastname: Fedorenko
authors.affiliation: Department of Pharmacy, University of Groningen, Groningen, The Netherlands.
authors.forename: Bob
authors.initials: B
authors.lastname: Wilffert
authors.affiliation: Mental Health Research Institute, Tomsk, Russia.
authors.forename: Nikolay A
authors.initials: NA
authors.lastname: Bokhan
authors.affiliation: Department of Pharmacy, University of Groningen, Groningen, The Netherlands.
authors.forename: Jacobus R B J
authors.initials: JR
authors.lastname: Brouwers
authors.affiliation: Department of Pharmacy, University of Groningen, Groningen, The Netherlands; Mental Health Institute Westelijk Noord-Brabant, Halsteren, The Netherlands. Electronic address: a.j.m.loonen@rug.nl.
authors.forename: Anton J M
authors.initials: AJ
authors.lastname: Loonen
mesh_terms: D000483:Alleles; D003430:Cross-Sectional Studies; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood / Q000378:metabolism*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D009069:Movement Disorders / Q000150:complications / Q000175:diagnosis / Q000235:genetics* / Q000517:prevention & control; D020641:Polymorphism, Single Nucleotide; D012559:Schizophrenia / Q000150:complications / Q000235:genetics; D012569:Schizotypal Personality Disorder / Q000150:complications / Q000235:genetics; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics*
chemical_list: D019314:Dehydroepiandrosterone Sulfate; D013254:Steroid 17-alpha-Hydroxylase
keywords: Cyp17; Dehydroepiandrosterone; Tardive dyskinesia