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.
Highlights
Dyskinesia is a collective name for a variety of involuntary hyperkinetic movements (Loonen and Van Praag, 2007)
A significant association was established between the functional mutation N251S-polymorphism of the PIP5K2A gene and tardive dyskinesia, while the other 2 examined nonfunctional single nucleotide polymorphisms were not related
Our finding suggests that Levodopa-induced dyskinesia (LID) is related to a similar NMDA receptor-related malfunctioning of dopamine-D2 receptor carrying indirect pathway medium-sized spiny neurons (MSNs) as Huntington’s disease (HD)
Summary
Dyskinesia is a collective name for a variety of involuntary hyperkinetic movements (Loonen and Van Praag, 2007). TD is a potentially disabling irreversible movement disorder, which has a prevalence of around 30% in patients chronically exposed to antipsychotics (Kane et al, 1988; Glazer, 2000) It can be subdivided into orofaciolingual (TDof) and limb-truncal (TDlt) dyskinesia (Al Hadithy et al, 2009, 2010). 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
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