No evidence so far of a major role of AKT1 and GSK3B in the pathogenesis of antipsychotic-induced tardive dyskinesia

Anastasia Levchenko; Natalya Vyalova; Ivan V Pozhidaev; Anastasiia S Boiko; Diana Z Osmanova; Olga Yu Fedorenko; Arkadiy V Semke; Nikolay A Bokhan; Bob Wilffert; Anton J M Loonen; Svetlana A Ivanova

doi:10.1002/hup.2685

No evidence so far of a major role of AKT1 and GSK3B in the pathogenesis of antipsychotic-induced tardive dyskinesia

Hum Psychopharmacol. 2019 Jan;34(1):e2685. doi: 10.1002/hup.2685. Epub 2019 Jan 8.

Authors

Anastasia Levchenko¹, Natalya Vyalova², Ivan V Pozhidaev², Anastasiia S Boiko², Diana Z Osmanova², Olga Yu Fedorenko^{2

3}, Arkadiy V Semke², Nikolay A Bokhan^{2

4}, Bob Wilffert^{5

6}, Anton J M Loonen^{5

7}, Svetlana A Ivanova^{2

3}

Affiliations

¹ Institute of Translational Biomedicine, Saint Petersburg State University, Saint Petersburg, Russia.
² Tomsk National Research Medical Center of the Russian Academy of Sciences, Mental Health Research Institute, Tomsk, Russia.
³ Division for Control and Diagnostics, School of Non-Destructive Testing & Security, National Research Tomsk Polytechnic University, Tomsk, Russia.
⁴ Department of Psychotherapy and Psychological Counseling, National Research Tomsk State University, Tomsk, Russia.
⁵ Unit of PharmacoTherapy, Epidemiology and Economics, Groningen Research Institute of Pharmacy, University of Groningen, Groningen, The Netherlands.
⁶ Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
⁷ GGZ Westelijk Noord-Brabant, Bergen op Zoom, The Netherlands.

PMID: 30623492
DOI: 10.1002/hup.2685

Abstract

Objective: AKT1 and GSK3B take part in one of the intracellular cascades activated by the D2 dopamine receptor (DRD2). This receptor is antagonized by antipsychotics and plays a role in the pathogenesis of antipsychotic-induced tardive dyskinesia (TD). The present study investigated association of several polymorphisms in the two candidate genes, AKT1 and GSK3B, with TD in antipsychotic-treated patients with schizophrenia.

Methods: DNA samples from 449 patients from several Siberian regions (Russia) were genotyped, and the results were analyzed using chi-squared tests and analyses of variance.

Results: Antipsychotic-induced TD was not associated with either of the tested functional polymorphisms (rs334558, rs1130214, and rs3730358).

Conclusions: Despite regulation of AKT1 and GSK3B by DRD2, we found no evidence that these two kinases play a major role in the pathogenesis of antipsychotic-induced TD. These results agree with previously published data and necessitate further exploration of other pathogenic mechanisms, such as neurotoxicity due to excessive dopamine metabolism.

Keywords: AKT1; GSK3B; antipsychotics; pharmacogenetics; schizophrenia; tardive dyskinesia.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Antipsychotic Agents / adverse effects*
Female
Glycogen Synthase Kinase 3 beta / genetics
Glycogen Synthase Kinase 3 beta / physiology*
Humans
Male
Middle Aged
Polymorphism, Single Nucleotide
Proto-Oncogene Proteins c-akt / genetics
Proto-Oncogene Proteins c-akt / physiology*
Receptors, Dopamine D2 / physiology
Tardive Dyskinesia / chemically induced*

Substances

Antipsychotic Agents
Receptors, Dopamine D2
AKT1 protein, human
GSK3B protein, human
Glycogen Synthase Kinase 3 beta
Proto-Oncogene Proteins c-akt

Grants and funding

30/Siberian Branch, Russian Academy of Sciences/International