Genetics of tardive dyskinesia: Promising leads and ways forward

Abstract

Tardive dyskinesia (TD) is a potentially irreversible and often debilitating movement disorder secondary to chronic use of dopamine receptor blocking medications. Genetic factors have been implicated in the etiology of TD. We therefore have reviewed the most promising genes associated with TD, including DRD2, DRD3, VMAT2, HSPG2, HTR2A, HTR2C, and SOD2. In addition, we present evidence supporting a role for these genes from preclinical models of TD. The current understanding of the etiogenesis of TD is discussed in the light of the recent approvals of valbenazine and deutetrabenazine, VMAT2 inhibitors, for treating TD.

Keywords: Dopamine D(2) receptor gene (DRD2); Dopamine D(3) receptor gene (DRD3); Heparan sulfate proteoglycan 2 (HSPG2); Manganese superoxide dismutase (SOD2); Pathophysiology; Pharmacogenetics; Serotonin 2A receptor (HTR2A); Serotonin 2C receptor (HTR2C); Tardive dyskinesia (TD); Vesicular monoamine transporter 2 gene (VMAT2/SLC18A2).