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 language | English |
|---|---|
| Pages (from-to) | 172-177 |
| Number of pages | 6 |
| Journal | Progress in Neuro-Psychopharmacology and Biological Psychiatry |
| Volume | 50 |
| DOIs | |
| Publication status | Published - 3 Apr 2014 |
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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 journal › Article
}
TY - JOUR
T1 - Dehydroepiandrosterone sulphate as a putative protective factor against tardive dyskinesia
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
PY - 2014/4/3
Y1 - 2014/4/3
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.
AB - 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.
KW - Cyp17
KW - Dehydroepiandrosterone
KW - Tardive dyskinesia
UR - http://www.scopus.com/inward/record.url?scp=84892455159&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84892455159&partnerID=8YFLogxK
U2 - 10.1016/j.pnpbp.2013.12.015
DO - 10.1016/j.pnpbp.2013.12.015
M3 - Article
VL - 50
SP - 172
EP - 177
JO - Progress in Neuro-Psychopharmacology and Biological Psychiatry
JF - Progress in Neuro-Psychopharmacology and Biological Psychiatry
SN - 0278-5846
ER -