New Models of Frontal-Subcortical Skeletomotor Circuit Pathology in Tardive Dyskinesia

Abstract

Tardive dyskinesia (TD) is a hyperkinetic movement disorder that can occur as a side effect of treatment with antipsychotic medications. Because antipsychotics block the D2 family of dopamine receptors in the striatum, it has long been suspected this blockade contributes to the development of TD. Specifically, increased sensitivity of the dopamine receptors following chronic blockade has been thought to result in abnormal functioning of the frontal-subcortical (FSC) skeletomotor circuit and the symptoms of TD. However, this hypothesis remains unproven. In recent years, substantial research has focused on the basal ganglia and FSC circuits. This research has resulted in the development of the focused selection model of skeletomotor circuit function. This hypothesis provides a compelling model of neurocircuit abnormalities in TD. A greater understanding of the neuropathology of TD may lead to the development of better treatment and prevention strategies for this disorder. Furthermore, this information may contribute to a more complete understanding of normal skeletomotor circuit function and the role of circuit pathology in numerous neuropsychiatric conditions.