title: Likelihood of mechanistic roles for dopaminergic, serotonergic and glutamatergic receptors in tardive dyskinesia: A comparison of genetic variants in two independent patient populations.
abstract: OBJECTIVE
  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.
authors.affiliation: Mental Health Research Institute, Tomsk, Russian Federation; National Research Tomsk Polytechnic University, Tomsk, Russian Federation.
authors.forename: Svetlana A
authors.initials: SA
authors.lastname: Ivanova
authors.affiliation: Department of Pharmacy, University of Groningen, Groningen, The Netherlands; GGZ Westelijk Noord-Brabant, Bergen op Zoom, The Netherlands.
authors.forename: Anton Jm
authors.initials: AJ
authors.lastname: Loonen
authors.affiliation: Psychiatric Centre GGZ Centraal, Amersfoort, The Netherlands; Department of Psychiatry and Psychology, South Limburg Mental Health Research and Teaching Network, EURON, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: P Roberto
authors.initials: PR
authors.lastname: Bakker
authors.affiliation: Research Institute for Medical Genetics, Tomsk, Russian Federation.
authors.forename: Maxim B
authors.initials: MB
authors.lastname: Freidin
authors.affiliation: Department of Pharmacy, University of Groningen, Groningen, The Netherlands.
authors.forename: Nienke J
authors.initials: NJ
authors.lastname: Ter Woerds
authors.affiliation: Department of Pharmacy, University of Groningen, Groningen, The Netherlands; Parnassia Group, Pharmacy Haaglanden, The Hague, The Netherlands.
authors.forename: Asmar Fy
authors.initials: AF
authors.lastname: Al Hadithy
authors.affiliation: Mental Health Research Institute, Tomsk, Russian Federation.
authors.forename: Arkadiy V
authors.initials: AV
authors.lastname: Semke
authors.affiliation: Mental Health Research Institute, Tomsk, Russian Federation; National Research Tomsk Polytechnic University, Tomsk, Russian Federation.
authors.forename: Olga Yu
authors.initials: OY
authors.lastname: Fedorenko
authors.affiliation: Department of Pharmacy, University of Groningen, Groningen, The Netherlands.
authors.forename: Jacobus Rbj
authors.initials: JR
authors.lastname: Brouwers
authors.affiliation: Mental Health Research Institute, Tomsk, Russian Federation; National Research Tomsk State University, Tomsk, Russian Federation.
authors.forename: Nikolay A
authors.initials: NA
authors.lastname: Bokhan
authors.affiliation: Department of Psychiatry and Psychology, South Limburg Mental Health Research and Teaching Network, EURON, Maastricht University Medical Centre, Maastricht, The Netherlands; Department of Psychosis Studies, Institute of Psychiatry, King's Health Partners, King's College London, London, UK.
authors.forename: Jim
authors.initials: J
authors.lastname: van Os
authors.affiliation: Psychiatric Centre GGZ Centraal, Amersfoort, The Netherlands; Department of Psychiatry and Psychology, South Limburg Mental Health Research and Teaching Network, EURON, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Peter N
authors.initials: PN
authors.lastname: van Harten
authors.affiliation: Department of Pharmacy, University of Groningen, Groningen, The Netherlands; Department of Clinical Pharmacy and Pharmacology, University Medical Centre Groningen, Groningen, The Netherlands.
authors.forename: Bob
authors.initials: B
authors.lastname: Wilffert
keywords: NMDA receptor; Tardive dyskinesia mechanism; dopaminergic receptor; genetic variants; glutamatergic receptor; serotonergic receptor