Aims: Neurodegenerative processes may be involved in the pathogenesis of tardive dyskinesia (TD), and a growing body of evidence suggests that brain-derived neurotrophic factor (BDNF) plays a role in both the antipsychotic effects and the pathogenesis of TD. BDNF and glycogen synthase kinase (GSK)-3β are important in neuronal survival, and thus abnormal regulation of BDNF and GSK-3β may contribute to TD pathophysiology. This study investigated the relationship between two polymorphisms, val66met in the BDNF coding region and -50T/C in the GSK-3β promoter, and susceptibility to TD among a matched sample of patients having schizophrenia with TD (n = 83), patients with schizophrenia without TD (n = 78), and normal control subjects (n = 93).
Methods: All subjects were Korean. The BDNF val66met and GSK-3β-50T/C genotypes were determined by polymerase chain reaction and restriction fragment length polymorphism analyses.
Results: Polymerase chain reaction analysis revealed no significant difference in the occurrence of the polymorphisms among the TD, non-TD, and control subjects, but a significant interaction was observed among the groups possessing BDNF val allele in compound genotypes (P = 0.001). We found that the schizophrenic subjects with the C/C GSK-3β genotype, who carry the val allele of the BDNF gene, are expected to have a decreased risk of developing neuroleptic-induced tardive dyskinesia (P < 0.001).
Conclusions: Our results demonstrate that the GSK-3β C/C genotype with the BDNF val allele is associated with patients having schizophrenia without TD. This study also suggests that the BDNF and GSK-3β gene polymorphisms work in combination, but not individually, in predisposing patients with schizophrenia to TD.