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Tardive dyskinesia, dehydroepiandrosterone sulfate and cytochrome P450c17a gene polymorphism in psychiatric inpatients

Ivanova, S. A., Geers, L. M., Al Hadithy, A. F. Y., Pechlivanoglou, P., Semke, A. V., Vyalova, N. M., Fedorenko, O. Y., Brouwers, J. R. B. J., Wilffert, B. & Loonen, A. J. M., 1-Oct-2014, In : European Neuropsychopharmacology. 24, S2, p. 486-487 2 p.

Research output: Contribution to journalArticleAcademicpeer-review

  • S.A. Ivanova
  • L.M. Geers
  • A.F.Y. Al Hadithy
  • P. Pechlivanoglou
  • A.V. Semke
  • N.M. Vyalova
  • O.Y. Fedorenko
  • J.R.B.J. Brouwers
  • B. Wilffert
  • A.J.M. Loonen
Tardive dyskinesia (TD) is a potentially irreversible antipsychoticinduced movement disorder with a prevalence of about 20-30% in psychiatric patients chronically exposed to antipsychotics. A wellknown theory states that TD is 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 P450c17a (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: TD was assessed cross-sectionally by the use of the Abnormal Involuntary Movement Scale (AIMS) in in 146 Caucasian psychiatric inpatients from Siberia. TDof and TDlt were assessed with AIMS items 1-4 and 5-7, respectively. The DHEAs levels were tested with aid of the DHEA-S ELISA Kit, (DRG International Inc.). DNA extraction and fluorogenic 5′-exonuclease TaqMan genotyping assays were conducted according to standard protocols and blind to the clinical status of the subjects [1]. The statistical software 'R' was used for the calculations. For creating an overview of the clinical and demographic features of the study population, excel and the statistical SPSS software, release 17, for Windows were used. The deviation from the Hardy-Weinberg Equilibrium was tested by the chi-squared test for the Cyp17 polymorphisms. Results: In total 146 patient with clinical diagnosis of schizophrenia or schizotypal disorder (ICD-10: F20 and F21, respectively) were included of which 91 males and 55 females. Demographic and clinical details have been provided with elsewhere [1,2]. The genotype distribution in the total population and by gender shows that the female patients of this population are more often carrier of the Cyp17 CC genotype compared to male patients. The results of the logistic regression analysis of the influence of the Cyp17 T-allele and the level of DHEAS on the occurrence of TD, TDof and TDlt indicate that carriers of the Cyp17 genotype CC have a significant lower risk of developing TD compared to carriers of the Cyp17 genotypes TC or TT (p
Original languageEnglish
Pages (from-to)486-487
Number of pages2
JournalEuropean Neuropsychopharmacology
Volume24
Issue numberS2
Publication statusPublished - 1-Oct-2014

    Keywords

  • prasterone sulfate, cytochrome, prasterone, antioxidant, exonuclease, neuroleptic agent, steroid, enzyme, DNA, tardive dyskinesia, DNA polymorphism, hospital patient, human, college, psychopharmacology, genotype, patient, population, allele, male, female, computer program, neurotoxicity, gender, hypothesis, prevalence, biosynthesis, schizophrenia, gene, single nucleotide polymorphism, diagnosis, motor dysfunction, assay, oxidative stress, DNA extraction, diagnosis related group, ELISA kit, Russian Federation, Abnormal Involuntary Movement Scale, mental patient, limb, protein processing, diseases, ICD-10, logistic regression analysis, risk, Caucasian, data analysis software, enzyme linked immunosorbent assay

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