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Do Tardive Dyskinesia and l-Dopa Induced Dyskinesia Share Common Genetic Risk Factors? An Exploratory Study

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Abstract

Tardive dyskinesia (TD) in schizophrenia patients treated with antipsychotic medications and l-dopa induced dyskinesia (LID) among Parkinson's disease (PD) affected individuals share similar clinical features. Both conditions are induced by chronic exposure to drugs that target dopaminergic receptors (antagonists in TD and agonists in LID) and cause pulsatile and nonphysiological stimulation of these receptors. We hypothesized that the two motor adverse effects partially share genetic risk factors such that certain genetic variants exert a pleiotropic effect, influencing susceptibility to TD as well as to LID. In this pilot study, we focused on 21 TD-associated SNPs, previously reported in TD genome-wide association studies or in candidate gene studies. By applying logistic regression and controlling for relevant clinical risk factors, we studied the association of the SNPs with LID vulnerability in two independent pharmacogenetic samples. We included a Jewish Israeli sample of 203 PD patients treated with l-dopa for a minimum of 3 years and evaluated the existence or absence of LID (LID+ = 128; LID− = 75). An Italian sample was composed of early LID developers (within the first 3 years of treatment, N = 187) contrasted with non-early LID developers (after 7 years or more of treatment, N = 203). None of the studied SNPs were significantly associated with LID susceptibility in the two samples. Therefore, we were unable to obtain proof of concept for our initial hypothesis of an overlapping contribution of genetic risk factors to TD and LID. Further studies in larger samples are required to reach definitive conclusions.

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Acknowledgments

This study was supported in part by a Rapid Response Innovation grant from the Michael J. Fox Foundation for Parkinson's Research. The Italian DNA samples were from the “Parkinson Biobank” of the Parkinson Institute, Istituti Clinici di Perfezionamento, Italy (www.parkinsonbiobank.com). This biobank is part of the Telethon Genetic Biobank Network (http://www.biobanknetwork.org) supported by TELETHON Italy (project no. GTB07001) and by the “Fondazione Grigioni per il Morbo di Parkinson.”

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Authors and Affiliations

  1. Biological Psychiatry Laboratory, Department of Psychiatry, Hadassah-Hebrew University Medical Center, Ein Karem, Jerusalem, 91120, Israel

    Lior Greenbaum, Polina Zozulinsky, Tzuri Lifschytz & Bernard Lerer

  2. Department of Neurology, Chaim Sheba Medical Center, Tel Hashomer, Israel

    Lior Greenbaum, Oren S. Cohen, Gilad Yahalom, Rivka Inzelberg & Sharon Hassin-Baer

  3. Parkinson Institute, Istituti Clinici di Perfezionamento, Milan, Italy

    Stefano Goldwurm, Roberto Cilia & Silvana Tesei

  4. Parkinson’s Disease and Movement Disorders Clinic, Chaim Sheba Medical Center, Tel Hashomer, Israel

    Oren S. Cohen, Gilad Yahalom, Rivka Inzelberg & Sharon Hassin-Baer

  5. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

    Oren S. Cohen, Rivka Inzelberg & Sharon Hassin-Baer

  6. Dipartimento di Biologia e Genetica per le Scienze Mediche, Università degli Studi di Milano, Milan, Italy

    Rosanna Asselta

  7. Jerusalem Mental Health Center, Eitanim Psychiatric Hospital, Jerusalem, Israel

    Yoav Kohn

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  1. Lior Greenbaum
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  2. Stefano Goldwurm
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Correspondence to Bernard Lerer.

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Greenbaum, L., Goldwurm, S., Zozulinsky, P. et al. Do Tardive Dyskinesia and l-Dopa Induced Dyskinesia Share Common Genetic Risk Factors? An Exploratory Study. J Mol Neurosci 51, 380–388 (2013). https://doi.org/10.1007/s12031-013-0020-x

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