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Dehydroepiandrosterone sulphate as a putative protective factor against tardive dyskinesia

Ivanova, S. A., Geers, L. M., Al Hadithy, A. F. Y., Pechlivanoglou, P., Semke, A. V., Vyalova, N. M., Rudikov, E. V., Fedorenko, O. Y., Wilffert, B., Bokhan, N. A., Brouwers, J. R. B. J. & Loonen, A. J. M., 3-Apr-2014, In : Progress in Neuro-Psychopharmacology & Biological Psychiatry. 50, p. 172-177 6 p.

Research output: Contribution to journalArticleAcademicpeer-review

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 P450c17 alpha (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).

Method: 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. (C) 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Original languageEnglish
Pages (from-to)172-177
Number of pages6
JournalProgress in Neuro-Psychopharmacology & Biological Psychiatry
Volume50
Publication statusPublished - 3-Apr-2014

    Keywords

  • Cyp17, Dehydroepiandrosterone, Tardive dyskinesia, cytochrome P450 family 17, prasterone sulfate, article, biosynthesis, blood level, blood sampling, clinical effectiveness, clinical feature, controlled study, CYP17 gene, disease activity, disease association, disease severity, drug efficacy, female, gene, gene frequency, gene function, gene identification, genetic polymorphism, genetic variability, genotype, hormone action, human, major clinical study, male, molecular pathology, neuroprotection, neurotoxicity, outcome assessment, patient assessment, scoring system, sex hormone determination, tardive dyskinesia

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