No involvement of the adenosine A2A receptor in tardive dyskinesia in Russian psychiatric inpatients from Siberia

Mental Health Research Institute SB RAMSci, Tomsk, Russian Federation.
Human Psychopharmacology Clinical and Experimental (Impact Factor: 2.19). 05/2012; 27(3):334-7. DOI: 10.1002/hup.2226
Source: PubMed


The adenosine A2A receptor forms a heteromeric complex with the striatal dopamine D2 receptor. We examined whether a specific polymorphism in adenosine A2A receptor (2592 C/Tins) is associated with tardive dyskinesia.
Tardive dyskinesia was assessed cross-sectionally in 146 Caucasian psychiatric inpatients from Siberia.
Between-group comparisons of genotypic or allelic frequencies showed no statistically significant difference. Logistic regression analysis with the occurrence of tardive dyskinesia as dependent variable showed no significant association with age, duration of illness, gender, and genotype.
The interaction between the A2A and D2 receptors seems not involved in the development of tardive dyskinesia.

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    • "In total 146 patient were included of which 91 males and 55 females. Demograpic and clinical details have been provided elsewhere (Al Hadithy et al., 2009; Ivanova et al., 2012a). There is no significant difference in average age and gender proportions between persons of which the DHEAs values were available and persons with missing DHEAs values. "
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    ABSTRACT: 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. 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)? Tardive dyskinesia was assessed cross-sectionally in 146 Caucasian psychiatric inpatients from Siberia. 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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