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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. (2013) DRD2/ANKK1 Taq1A (rs 1800497 C>T) genotypes are associated with susceptibility to second generation antipsychotic-induced akathisia. Journal of Psychopharmacology, 27(4), pp. 343-348.

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    Abstract

    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.

    Impact and interest:

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    ID Code: 55211
    Item Type: Journal Article
    Keywords: Akathisia, dopamine 2 receptor, ANNK1, genetic association, antipsychotic drugs
    DOI: 10.1177/0269881112463469
    ISSN: 1461-7285
    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 2013 Sage Publications Ltd.
    Deposited On: 30 Nov 2012 11:48
    Last Modified: 27 Nov 2013 22:20

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