Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Multicenter Study
. 2014 Dec 28;18(6):pyu098.
doi: 10.1093/ijnp/pyu098.

Association study indicates a protective role of phosphatidylinositol-4-phosphate-5-kinase against tardive dyskinesia

Olga Yu Fedorenko  1 , Anton J M Loonen  2 , Florian Lang  1 , Valentina A Toshchakova  1 , Evgenia G Boyarko  1 , Arkadiy V Semke  1 , Nikolay A Bokhan  1 , Nikolay V Govorin  1 , Lyubomir I Aftanas  1 , Svetlana A Ivanova  1
Affiliations
Multicenter Study

Association study indicates a protective role of phosphatidylinositol-4-phosphate-5-kinase against tardive dyskinesia

Olga Yu Fedorenko et al. Int J Neuropsychopharmacol. .

Abstract

Background: Tardive dyskinesia is a disorder characterized by involuntary muscle movements that occur as a complication of long-term treatment with antipsychotic drugs. It has been suggested to be related to a malfunctioning of the indirect pathway of the motor part of the cortical-striatal-thalamic-cortical circuit, which may be caused by oxidative stress-induced neurotoxicity.

Methods: The purpose of our study was to investigate the possible association between phosphatidylinositol-4-phosphate-5-kinase type IIa (PIP5K2A) function and tardive dyskinesia in 491 Caucasian patients with schizophrenia from 3 different psychiatric institutes in West Siberia. The Abnormal Involuntary Movement Scale was used to assess tardive dyskinesia. Individuals were genotyped for 3 single nucleotide polymorphisms in PIP5K2A gene: rs10828317, rs746203, and rs8341.

Results: A significant association was established between the functional mutation N251S-polymorphism of the PIP5K2A gene (rs10828317) and tardive dyskinesia, while the other 2 examined nonfunctional single nucleotide polymorphisms were not related.

Conclusions: We conclude from this association that PIP5K2A is possibly involved in a mechanism protecting against tardive dyskinesia-inducing neurotoxicity. This corresponds to our hypothesis that tardive dyskinesia is related to neurotoxicity at striatal indirect pathway medium-sized spiny neurons.

Keywords: PIP5K2A; gene polymorphism; medium spiny neurons; neurotoxicity; schizophrenia; tardive dyskinesia.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
The cortical-striatal-thalamic-cortical circuits, including the indirect and direct pathways. Activation of the direct pathway causes hyperkinesia and activation of the indirect pathway causes hypokinesia. ENK, enkephalin; GPe, globus pallidus, external segment; GPi, globus pallidus, internal segment; SNc, substantia nigra, pars compacta; SNr, substantia nigra, pars reticulata; SP/DYN, substance P/dynorphin; STh, subthalamic nucleus; D1, D2, medium-sized spiny neurons (MSNs) with D1 or D2 receptors. Red, excitatory (glutamatergic, dopaminergic); blue, inhibitory (GABAergic, dopaminergic).
Figure 2.
Figure 2.
Representation of the single nucleotide polymorphism positions of 3 studied polymorphisms of the PIP5K2A gene (He et al., 2007).
See this image and copyright information in PMC

References

    1. Al Hadithy AF, Ivanova SA, Pechlivanoglou P, Semke A, Fedorenko O, Kornetova E, Ryadovaya L, Brouwers JR, Wilffert B, Bruggeman R, Loonen AJ. (2009). Tardive dyskinesia and DRD3, HTR2A and HTR2C gene polymorphisms in Russian psychiatric inpatients from Siberia. Prog Neuropsychopharmacol Biol Psychiatry 33:475–481. - PubMed
    1. Al Hadithy AF, Ivanova SA, Pechlivanoglou P, Wilffert B, Semke A, Fedorenko O, Kornetova E, Ryadovaya L, Brouwers JR, Loonen AJ. (2010). Missense polymorphisms in three oxidative-stress enzymes (GSTP1, SOD2, and GPX1) and dyskinesias in Russian psychiatric inpatients from Siberia. Hum Psychopharmacol 25:84–91. - PubMed
    1. Andreasen NC, Pressler M, Nopoulos P, Miller D, Ho BC. (2010). Antipsychotic dose equivalents and dose-years: a standardized method for comparing exposure to different drugs. Biol Psychiatry 67:255–262. - PMC - PubMed
    1. Bakker SC, Hoogendoorn ML, Hendriks J, Verzijlbergen K, Caron S, Verduijn W, Selten JP, Pearson PL, Kahn RS, Sinke RJ. (2007). The PIP5K2A and RGS4 genes are differentially associated with deficit and non-deficit schizophrenia. Genes Brain Behav 6:113–119. - PubMed
    1. Benjamini Y, Hochberg Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc B. 1995;57:289–300.

Publication types

MeSH terms

Substances