DRD2/ANKK1 Taq1A (rs 1800497 C>T) genotypes are associated with susceptibility to second generation antipsychotic-induced akathisia
Lawford, B., Barnes, M., Swagell, C., Connor, J., Burton, S., Heslop, K., Voisey, J., Morris, C. Phillip, Nyst, P., Noble, E., & Young, R. (2012) DRD2/ANKK1 Taq1A (rs 1800497 C>T) genotypes are associated with susceptibility to second generation antipsychotic-induced akathisia. Journal of Psychopharmacology. (In Press)
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Rationale Although the advent of atypical, second-generation antipsychotics (SGAs) has resulted in reduced likelihood of akathisia, this adverse effect remains a problem. Extrapyramidal adverse effects are associated with increased drug occupancy of dopamine 2 receptors (DRD2). The A1 allele of the DRD2/ANKK1,rs1800497, is associated with decreased striatal DRD2 density.
Objectives The aim of this study was to identify whether the A1(T) allele of the DRD2/ANKK1 was associated with akathisia (measured with the Barnes Akathisia Rating Scale) in a clinical sample of 234 patients treated with antipsychotics.
Results Definite akathisia (a score≥ 2 for the global clinical assessment of akathisia) was significantly less common in subjects prescribed SGAs (16.8 %) than those prescribed FGAs (47.6%), p<0.0001. Overall, 24.1% of A1+ (A1A2/A1A1) patients treated with SGAs had akathisia compared to 10.8% of A1- (A2A2) patients. A1+ (A1A2/A1A1) patients administered SGAs also had higher global clinical assessment of akathisia scores than A1- subjects (p=0.01). SGAs maintained their advantage over FGAs regarding akathisia even in A1+ patients treated with SGAs.
Conclusions These results strongly suggest that A1+ variants of the DRD2/ANKK1 Taq1A allele confer risk for akathisia in patients treated with SGAs and may explain inconsistencies across prior studies comparing FGAs and SGAs.
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|Item Type:||Journal Article|
|Keywords:||Akathisia, dopamine 2 receptor, ANNK1, genetic association, antipsychotic drugs|
|Subjects:||Australian and New Zealand Standard Research Classification > BIOLOGICAL SCIENCES (060000) > BIOCHEMISTRY AND CELL BIOLOGY (060100)|
Australian and New Zealand Standard Research Classification > BIOLOGICAL SCIENCES (060000) > GENETICS (060400)
Australian and New Zealand Standard Research Classification > PSYCHOLOGY AND COGNITIVE SCIENCES (170000)
|Divisions:||Current > QUT Faculties and Divisions > Faculty of Health|
Current > Institutes > Institute of Health and Biomedical Innovation
|Copyright Owner:||Copyright 2012 Sage Publications Ltd.|
|Deposited On:||30 Nov 2012 11:48|
|Last Modified:||03 Dec 2012 23:35|
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