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Ser9Gly dopamine D3 receptor polymorphism and spontaneous dyskinesia in never-medicated schizophrenic patients

Molecular Psychiatry volume 6, pages 6–7 (2001)Cite this article

SIR – Tardive dyskinesia (TD) is a frequent and potentially irreversible extrapyramidal side effect during long-term treatment with typical antipsychotic drugs. Risk factors for the development of TD include age, organic brain damage, psychiatric diagnosis and cumulative dose of neuroleptic medications. Genetic predisposition may also play a role in the etiology of TD. In line with this hypothesis, we have demonstrated an apparent association between homozyosity for the Gly-9 variant (2-2 genotype) of the dopamine D3 receptor (DRD3) and the presence of TD in neuroleptic-treated schizophrenic patients.1 This finding has recently been supported by other studies,234 although a non-replication has also recently been published.5 The DRD3 2-2 genotype may also predispose for drug-induced acute akathisia.6 It is therefore suggested that inheritance of the Gly-9 DRD3 allele is a genetic susceptibility factor for the development and persistence of dyskinesia.

Still, it is not clear whether the apparent association between the DRD3 genotype and risk for TD is linked to a neuroleptic-induced effect per se, or alternatively, that patients carrying the Gly-9 allele may represent a certain subtype of schizophrenia with a high prevalence of dyskinesia. We have recently observed that dyskinesia may appear with almost the same frequency among never-medicated and antipsychotic-treated schizophrenic patients in India, suggesting that dyskinesia in some cases may be an integral part of the illness, not solely associated with antipsychotic drug treatment.7 Moreover, orofacial dyskinesia can be observed in a relatively high proportion of drug-naive subjects with schizophrenia or schizophrenia spectrum personality.8910 Based on these data, we decided to investigate whether the apparent DRD3-mediated genetic risk for dyskinetic involuntary movements in schizophrenic patients could be due to the 2-2 genotype per se, as a component of a specific disease phenotype, irrespective of the use of antipsychotic medication. We report our findings in a sample of never-medicated schizophrenic subjects in India.

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Authors and Affiliations

  1. Dr Einar Martens’ Research Group for Biological Psychiatry, Center for Molecular Medicine, University of Bergen, Haukeland University Hospital, Norway

    R Løvlie & V M Steen

  2. Schizophrenia Research Foundation (SCARF), Chennai, India

    R Thara & R Padmavathi

  3. Department of Clinical Research, Crichton Royal Hospital, Dumfries, UK

    R G McCreadie

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  1. R Løvlie
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  2. R Thara
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  3. R Padmavathi
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  4. V M Steen
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  5. R G McCreadie
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Løvlie, R., Thara, R., Padmavathi, R. et al. Ser9Gly dopamine D3 receptor polymorphism and spontaneous dyskinesia in never-medicated schizophrenic patients. Mol Psychiatry 6, 6–7 (2001). https://doi.org/10.1038/sj.mp.4000822

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