The pathophysiologic basis of tardive dyskinesia

Area of Science:

• Neuroscience
• Pharmacology
• Movement Disorders

Background:

• Tardive dyskinesia (TD) is a neurological disorder associated with antipsychotic medications.
• The underlying mechanisms of persistent TD are not fully understood, with theories including structural brain changes or functional adaptations.

Purpose of the Study:

• To review the proposed mechanisms of tardive dyskinesia (TD) development.
• To evaluate the evidence for structural versus functional changes in the brain.
• To assess the role of dopamine (DA) and cholinergic systems in TD.

Main Methods:

• Review of existing neurohistopathological studies.
• Analysis of animal models investigating dopamine neuron responses to antipsychotics.
• Examination of in vitro studies on dopamine-sensitive adenylate cyclase and dopamine receptors.

Main Results:

• Neurohistopathological evidence for structural brain alterations in TD is limited.
• Functional adaptive changes, such as dopamine (DA) supersensitivity, are proposed.
• DA supersensitivity may explain acute or reversible TD but not persistent forms.

Conclusions:

• The exact cause of persistent, drug-related tardive dyskinesia (TD) remains uncertain.
• Current evidence does not definitively support structural brain damage as the primary cause of persistent TD.
• Functional changes, particularly dopamine system adaptations, are implicated but require further investigation for long-term TD.