Antipsychotic-induced tardive dyskinesia: The role of glutamatergic system

Abstract

Tardive dyskinesia (TD) occurs in 20–25% of patients with long-term antipsychotic therapy. Abnormalities in glutamatergic transmission are considered one of the key components of the pathogenesis of drug-induced side effects. Glutamate acts as excitotoxin under certain conditions and in excessive concentrations.

Aim is to study the concentration of glutamate and analysis of single nucleotide polymorphisms (SNP) in genes coding the glutamate transporter and NMDA-receptors in schizophrenic patients with TD and without it.

The study group included 156 patients with schizophrenia receiving long-term antipsychotic treatment. Patients were divided into two groups: 63 patients with TD and 93 patients without it. Glutamate was determined in serum by spectrophotometric method. Determination of allelic variants of gene SLC1A2 (rs4354668) and GRIN2A (rs2650427, rs1969060) was performed by polymerase chain reaction in real-time.

We found a significant (P < 0.05) increase of the concentration of glutamate in patients with TD. Significant (P < 0.05) reduction in frequency of genotype GG of GRIN2A (rs1969060) and TT of SLC1A2 (rs4354668) were found in patients with TD in comparison to group without TD. In the study of glutamate concentration depending on the genotype GRIN2A (rs1969060) and genotype SLC1A2 (rs4354668) we observed a statistically significant change: elevated levels of glutamic acid identified with the heterozygous genotype in patients.

It is possible to suggest that reduction in frequency of these genotypes increases the risk of movement disorders due to the protective effect of these genotypes.

Disclosure of interest

The authors have not supplied their declaration of competing interest.