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Influence of ANKK1 and DRD2 polymorphisms in response to haloperidol

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Abstract

The present study explores whether ankyrin repeat and kinase domain containing 1 (ANKK1) and dopamine receptor D2 (DRD2) variants could predict efficacy and tolerability of haloperidol in the treatment of psychotic patients. We also attempted to replicate findings in a group of schizophrenic patients from the Clinical Antipsychotic Trials in Intervention Effectiveness (CATIE) study. Eighty-eight acutely psychotic patients were genotyped for 9 ANKK1 and 27 DRD2 SNPs. Treatment efficacy and tolerability were assessed using the Positive and Negative Symptoms Scale and the Udvalg for Kliniske Undersogelser side effects rating scales, respectively. Multivariate analyses were employed to test possible influences of single-nucleotide polymorphisms on clinical and safety variables. Analysis of haplotypes was also performed. Outcomes in the replication sample were response versus nonresponse and the presence versus absence of motor side effects at 1 month of treatment. rs2242592 within ANKK1 gene and rs1124493 within DRD2 gene were associated with clinical improvement (p = 0.008 and p = 0.001, respectively). Results were confirmed in the allelic analysis. Three haplotype blocks, one among ANKK1 and two among DRD2 gene were associated with better clinical improvement. Our results were not replicated in the CATIE sample, although rs11604671, which is in strong linkage disequilibrium with rs2242592, was associated with response in the replication sample. Our findings support a possible role of ANKK1 and DRD2 variability on haloperidol efficacy. However, due to the discrepancies between the results in the two samples, our results need further validation.

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Acknowledgments

The authors wish to thank the Clinical Antipsychotic Trials in Intervention Effectiveness (CATIE) Study Investigators Group.

Conflict of interest

None.

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Author notes

  1. Martin Schäfer

    Present address: Kliniken Essen Mitte, Essen, Germany

Authors and Affiliations

  1. Department of Psychiatry, Ludwig Maximilians University, Munich, Germany

    Ina Giegling, Martin Schäfer, Annette M. Hartmann, Marion Friedl, Bettina Konte, Philipp Krämer, Hans-Jürgen Möller & Dan Rujescu

  2. Institute of Psychiatry, University of Bologna, Viale Carlo Pepoli 5, 40123, Bologna, Italy

    Beatrice Balzarro, Stefano Porcelli, Diana De Ronchi & Alessandro Serretti

  3. Psychiatric University Hospital, Zurich, Switzerland

    Hans H. Stassen

  4. Department of Psychiatry, University of Halle, Halle, Germany

    Dan Rujescu

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  1. Ina Giegling
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Correspondence to Alessandro Serretti.

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Ina Giegling and Beatrice Balzarro have contributed equally.

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Giegling, I., Balzarro, B., Porcelli, S. et al. Influence of ANKK1 and DRD2 polymorphisms in response to haloperidol. Eur Arch Psychiatry Clin Neurosci 263, 65–74 (2013). https://doi.org/10.1007/s00406-012-0348-1

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