Likelihood of mechanistic roles for dopaminergic, serotonergic and glutamatergic receptors in tardive dyskinesia: A comparison of genetic variants in two independent patient populations

Svetlana A. Ivanova, Anton J.M. Loonen*, P. Roberto Bakker, Maxim B. Freidin, Nienke J. ter Woerds, Asmar F.Y. Al Hadithy, Arkadiy V. Semke, Olga Yu Fedorenko, Jacobus R.B.J. Brouwers, Nikolay A. Bokhan, Jim van Os, Peter N. van Harten, Bob Wilffert

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

12 Citations (Web of Science)


Objectives: An established theory for the pathogenesis of tardive dyskinesia is disturbed dopaminergic receptor sensitivity and/or dopaminergic intracellular signaling. We examined associations between genetic variants of neurotransmitter receptors and tardive dyskinesia.

Methods: We assessed tardive dyskinesia in Caucasian psychiatric inpatients from Siberia (N = 431) and a long-stay population from the Netherlands (N = 168). These patients were genotyped for 43 tag single nucleotide polymorphisms in five neurotransmitter receptor genes, and the results for the two populations were compared.

Results: Several significant associations with tardive dyskinesia were identified, but only GRIN2A (rs1345423) was found in both patient populations. This lack of agreement was probably due to the small effect size of the associations, the multiple testing and the small sample size of the Dutch patient population. After reviewing the literature, we propose that the constitutive stimulatory activity of serotonergic type 2 receptors may be relevant.

Conclusions: Inactivity of the serotonergic, type 2C receptor or blockade of these receptors by atypical antipsychotic drugs may decrease the vulnerability to develop tardive dyskinesia.

Original languageEnglish
Article number2050312116643673
Pages (from-to)1– 9
Number of pages9
JournalSAGE Open Medicine
Publication statusPublished - 2016


  • Tardive dyskinesia mechanism
  • dopaminergic receptor
  • serotonergic receptor
  • glutamatergic receptor
  • NMDA receptor
  • genetic variants

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