Dehydroepiandrosterone sulphate as a putative protective factor against tardive dyskinesia

Svetlana A. Ivanova, Lisanne M. Geers, Asmar F Y Al Hadithy, Petros Pechlivanoglou, Arkadiy V. Semke, Natalia M. Vyalova, Evgeniy V. Rudikov, Olga Y. Fedorenko, Bob Wilffert, Nikolay A. Bokhan, Jacobus R B J Brouwers, Anton J M Loonen

Research output: Contribution to journalArticle

3 Citations (Scopus)

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). 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.

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

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Dehydroepiandrosterone Sulfate
Cytochromes
Dehydroepiandrosterone
Genotype
Alleles
Siberia
Neuroprotective Agents
Antipsychotic Agents
Single Nucleotide Polymorphism
Psychiatry
Protective Factors
Tardive Dyskinesia
Inpatients
Oxidative Stress
Extremities
Antioxidants
Steroids
Enzymes
Genes

Keywords

  • Cyp17
  • Dehydroepiandrosterone
  • Tardive dyskinesia

ASJC Scopus subject areas

  • Biological Psychiatry
  • Pharmacology
  • Medicine(all)

Cite this

Dehydroepiandrosterone sulphate as a putative protective factor against tardive dyskinesia. / Ivanova, Svetlana A.; Geers, Lisanne M.; Al Hadithy, Asmar F Y; Pechlivanoglou, Petros; Semke, Arkadiy V.; Vyalova, Natalia M.; Rudikov, Evgeniy V.; Fedorenko, Olga Y.; Wilffert, Bob; Bokhan, Nikolay A.; Brouwers, Jacobus R B J; Loonen, Anton J M.

In: Progress in Neuro-Psychopharmacology and Biological Psychiatry, Vol. 50, 03.04.2014, p. 172-177.

Research output: Contribution to journalArticle

Ivanova, SA, Geers, LM, Al Hadithy, AFY, Pechlivanoglou, P, Semke, AV, Vyalova, NM, Rudikov, EV, Fedorenko, OY, Wilffert, B, Bokhan, NA, Brouwers, JRBJ & Loonen, AJM 2014, 'Dehydroepiandrosterone sulphate as a putative protective factor against tardive dyskinesia', Progress in Neuro-Psychopharmacology and Biological Psychiatry, vol. 50, pp. 172-177. https://doi.org/10.1016/j.pnpbp.2013.12.015
Ivanova, Svetlana A. ; Geers, Lisanne M. ; Al Hadithy, Asmar F Y ; Pechlivanoglou, Petros ; Semke, Arkadiy V. ; Vyalova, Natalia M. ; Rudikov, Evgeniy V. ; Fedorenko, Olga Y. ; Wilffert, Bob ; Bokhan, Nikolay A. ; Brouwers, Jacobus R B J ; Loonen, Anton J M. / Dehydroepiandrosterone sulphate as a putative protective factor against tardive dyskinesia. In: Progress in Neuro-Psychopharmacology and Biological Psychiatry. 2014 ; Vol. 50. pp. 172-177.
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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). 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.",
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AU - Ivanova, Svetlana A.

AU - Geers, Lisanne M.

AU - Al Hadithy, Asmar F Y

AU - Pechlivanoglou, Petros

AU - Semke, Arkadiy V.

AU - Vyalova, Natalia M.

AU - Rudikov, Evgeniy V.

AU - Fedorenko, Olga Y.

AU - Wilffert, Bob

AU - Bokhan, Nikolay A.

AU - Brouwers, Jacobus R B J

AU - Loonen, Anton J M

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N2 - 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). 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.

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