Dehydroepiandrosterone sulphate as a putative protective factor against tardive dyskinesia

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• 作者：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
• 关键词：AIC ; Akaike's Information Criterion ; AIMS ; Abnormal Involuntary Movement Scale ; CYP17 ; Cytochrome P450c17伪 ; DHEA(S) ; Dehydroepiandrosterone (sulphate) ; HWE ; Hardy&ndash ; Weinberg equilibrium ; MI ; Multiple imputation ; TD ; Tardive dyskinesia ; TDof ; Orofaciolingual tardive dyskinesia ; TDlt ; Limb-truncal tardive dyskinesia ; TDsum ; Both types tardive dyskinesia ; TPM ; Two part model
• 刊名：Progress in Neuro-Psychopharmacology and Biological Psychiatry
• 出版年：3 April, 2014
• 年：2014
• 卷：50
• 期：Complete
• 页码：172-177
• 全文大小：257 K

文摘

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伪 (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.