Emerging research suggests that immune system dysregulation may play a role in the development of tardive dyskinesia (TD), a movement disorder linked to long-term use of dopamine receptor-blocking antipsychotics. Rodent studies show increased levels of pro-inflammatory cytokines—such as IL-1β, IL-6, and TNF-α—in the striatum after chronic haloperidol use, often correlating with orofacial dyskinesia severity. However, human findings are inconsistent. Evidence points to neuroinflammation, particularly in the striosomal compartment of the striatum and lateral habenula, as a possible mechanism driving TD, especially its classic orofacial form.

This review proposes that TD may result not only from dopamine receptor sensitivity but also from neuroinflammatory processes involving both central and peripheral immune activation. Regions like the choroid plexus and epithalamus may influence nearby brain structures such as the dorsal diencephalic connection system, impacting motor regulation. Given the overlap between schizophrenia, antipsychotic treatment, and neuroimmune signaling, more research is needed to explore inflammation’s role in TD and identify potential therapeutic targets.

Reference: Loonen AJM. Putative role of immune reactions in the mechanism of tardive dyskinesia. Brain Behav Immun Health. 2023;33:100687. doi: 10.1016/j.bbih.2023.100687.